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Soh J, Park HS, Lee WY, Park SH, Kang KC. The effects of multimodal cocktail analgesic local injection in postoperative pain control after laminoplasty: A study protocol of a prospective randomized controlled trial. PLoS One 2025; 20:e0324791. [PMID: 40512737 PMCID: PMC12165372 DOI: 10.1371/journal.pone.0324791] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/28/2024] [Accepted: 04/20/2025] [Indexed: 06/16/2025] Open
Abstract
BACKGROUND Laminoplasty is the most widely used surgical technique for cervical spondylotic myelopathy. This surgery can cause severe postoperative pain; if not controlled, recovery or rehabilitation may be delayed. Therefore, effective control of postoperative pain is crucial. This randomized prospective study aims to evaluate the effects of a multimodal cocktail injection on postoperative pain and the efficacy of the protocol in patients undergoing posterior laminoplasty for cervical myelopathy. METHODS This single-center prospective randomized controlled trial focuses on patients diagnosed with cervical myelopathy or radiculopathy. This study will include patients aged 20-80 years who underwent laminoplasty. Participants will be divided into two groups: one group will receive a multimodal cocktail local injection during surgery and the other group will receive a local injection of normal saline only. The study is scheduled for a 3 month follow-up. The primary outcome measure will be the visual analog scale (VAS) score. Secondary outcome measures will be opioid and rescue analgesic consumption, time of initial analgesic requirement, adverse effects, and Japanese Orthopaedic Association (JOA) and neck disability index (NDI) scores. RESULTS AND CONCLUSIONS This is the first prospective randomized controlled trial to analyze the effects and safety of multimodal cocktail injections after cervical laminoplasty. Through this study, we anticipate that the demonstration of potential usefulness of multimodal cocktail analgesic injections in various aspects of spinal surgery, thereby this will provide a protocol for intraoperative cocktail injection. TRIAL REGISTRATION This trial was registered at the (https://www.clinicaltrial.gov), (NCT06113497) on 11/12/2023.
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Affiliation(s)
- Jaewan Soh
- Department of Orthopaedic Surgery, College of Medicine, Hanyang University Guri Hospital, Hanyang University, Guri, Republic of Korea
| | - Hong-Sik Park
- Department of Orthopaedic Surgery, College of Medicine, Kyung Hee University Hospital, Kyung Hee University, Seoul, Republic of Korea
| | - Won-Young Lee
- Department of Orthopaedic Surgery, College of Medicine, Kyung Hee University Hospital, Kyung Hee University, Seoul, Republic of Korea
| | - Se-Hwan Park
- Department of Orthopaedic Surgery, College of Medicine, Kyung Hee University Hospital, Kyung Hee University, Seoul, Republic of Korea
| | - Kyung-Chung Kang
- Department of Orthopaedic Surgery, College of Medicine, Kyung Hee University Hospital, Kyung Hee University, Seoul, Republic of Korea
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Jafal NM, Stoleru S, Zugravu A, Orban C, Popescu M, Marin RC, Fulga IG. The Analgesic Effect of Morphine on Peripheral Opioid Receptors: An Experimental Research. J Crit Care Med (Targu Mures) 2024; 10:337-344. [PMID: 39829726 PMCID: PMC11740696 DOI: 10.2478/jccm-2024-0042] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/08/2024] [Accepted: 10/28/2024] [Indexed: 01/22/2025] Open
Abstract
Opioids represent one of the key pillars in postoperative pain management, but their use has been associated with a variety of serious side effects. Thus, it is crucial to investigate the timing and course of opioid administration in order to ensure a best efficacy to side-effect profile. The aim of our article was to investigate the analgesic effects of locally administered morphine sulfate (intraplantar) in a carrageenan-induced inflammation model in rats. After carrageenan administration, the rats were divided into 10 equal groups and were injected with either morphine 5 mg/kg or 0.9% saline solution at different time intervals, depending on the assigned group. The analgesic effect was assessed through thermal stimulation. Our results showed that paw withdrawal time was significantly higher in rats treated with morphine compared to those in the control group 9.18 ± 3.38 compared to 5.14 ± 2.21 seconds, p=0.012). However, differences were more pronounced at certain time intervals post-carrageenan administration (at 180 minutes compared to 360 minutes, p=0.003 and at 180 minutes compare to 1440 minutes p<0.001), indicating that efficacy varies depending on the timing of treatment. In conclusion, our findings support the hypothesis that locally administered morphine may alleviate pain under inflammatory conditions and underscores the importance of considering treatment timing when evaluating the analgesic effect.
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Affiliation(s)
| | - Smaranda Stoleru
- “Carol Davila” University of Medicine and Pharmacy, Bucharest, Romania
| | - Aurelian Zugravu
- “Carol Davila” University of Medicine and Pharmacy, Bucharest, Romania
| | - Carmen Orban
- “Carol Davila” University of Medicine and Pharmacy, Bucharest, Romania
| | - Mihai Popescu
- “Carol Davila” University of Medicine and Pharmacy, Bucharest, Romania
| | | | - Ion-Gigel Fulga
- “Carol Davila” University of Medicine and Pharmacy, Bucharest, Romania
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Damiescu R, Dawood M, Elbadawi M, Klauck SM, Bringmann G, Efferth T. Identification of Cytisine Derivatives as Agonists of the Human Delta Opioid Receptor by Supercomputer-Based Virtual Drug Screening and Transcriptomics. ACS Chem Biol 2024; 19:1963-1981. [PMID: 39167688 DOI: 10.1021/acschembio.4c00231] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 08/23/2024]
Abstract
Delta opioid receptors (DORs) are rising as therapeutic targets, not only for the treatment of pain but also other neurological disorders (e.g., Parkinson's disease). The advantage of DOR agonists compared to μ-opioid receptor agonists is that they have fewer side effects and a lower potential to induce tolerance. However, although multiple candidates have been tested in the past few decades, none have been approved for clinical use. The current study focused on searching for new DOR agonists by screening a chemical library containing 40,000 natural and natural-derived products. The functional activity of the top molecules was evaluated in vitro through the cyclic adenosine monophosphate accumulation assay. Compound 3 showed promising results, and its activity was further investigated through transcriptomic methods. Compound 3 inhibited the expression of TNF-α, prevented NF-κB translocation to the nucleus, and activated the G-protein-mediated ERK1/2 pathway. Additionally, compound 3 is structurally different from known DOR agonists, making it a valuable candidate for further investigation for its anti-inflammatory and analgesic potential.
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Affiliation(s)
- Roxana Damiescu
- Department of Pharmaceutical Biology, Institute of Pharmaceutical and Biomedical Sciences, Johannes Gutenberg University, Staudinger Weg 5, Mainz 55099, Germany
| | - Mona Dawood
- Department of Pharmaceutical Biology, Institute of Pharmaceutical and Biomedical Sciences, Johannes Gutenberg University, Staudinger Weg 5, Mainz 55099, Germany
| | - Mohamed Elbadawi
- Department of Pharmaceutical Biology, Institute of Pharmaceutical and Biomedical Sciences, Johannes Gutenberg University, Staudinger Weg 5, Mainz 55099, Germany
| | - Sabine M Klauck
- Division of Cancer Genome Research, German Cancer Research Center (DKFZ) Heidelberg, National Center for Tumor Diseases (NCT), NCT Heidelberg, A Partnership between DKFZ and University Hospital Heidelberg, Heidelberg 69120, Germany
| | - Gerhard Bringmann
- Institute of Organic Chemistry, University of Würzburg, Am Hubland, Würzburg D-97074, Germany
| | - Thomas Efferth
- Department of Pharmaceutical Biology, Institute of Pharmaceutical and Biomedical Sciences, Johannes Gutenberg University, Staudinger Weg 5, Mainz 55099, Germany
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Zhou H, Zou D, Hong B, Hu R, Yang T, Li X, Li X, Hu J, Wang R, Wang Y. Gadolinium-based MR cisternography with prepontine cisternal routine for evaluating distribution pattern of intrathecal targeted drug delivery in pain management. Drug Deliv 2023; 30:2189588. [PMID: 36927215 PMCID: PMC10026817 DOI: 10.1080/10717544.2023.2189588] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/18/2023] Open
Abstract
Gadolinium-based MR cisternography has been mainly applied in clinical evaluation of cerebrospinal fluid leaking, that is conducted by intrathecal administration of contrast media. Recently, we have reported one novel technique of intrathecal targeted drug delivery with prepontine cisternal routine to treat orofacial cancer pain. The aim of this study was to examine the distribution pattern of this intrathecal drug delivery strategy. Here, we introduce one case who suffered severe orofacial pain caused by sublingual gland tumor, and successfully attenuated by prepontine cisternal administration of analgesic agents. To assess the distribution of intrathecal drugs, postoperative MR images of brain, cervical, thoracic, and lumbar segments in axial, coronal, and sagittal planes were obtained after application of gadolinium. The perfusion rate of contrast medium was set at 0.01 mmol per hour for 24 hours prior to MR scanning. In the T1-weighted images, we can identify contrast spread not only locating around the site of the intrathecal catheter tip, but also concentrated to the lateral sides. None obvious side effect was found after intrathecal injection of contrast media. Thus, our finding demonstrated the local distribution phenomenon of intrathecal drugs through prepontine cisternal access, and the bilateral perfusion pattern may provide insights underlying the analgesic mechanism of trigeminal pain provided by this novel intrathecal therapy. Gadolinium-based MR cisternography may serve as a potential tool to confirm the therapeutic effect of intrathecal targeted drug delivery via prepontine cisternal routine in orofacial pain management.
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Affiliation(s)
- Haocheng Zhou
- Department of Pain, The Third Xiangya Hospital and Institute of Pain Medicine, Central South University, Changsha, China
- Hunan Key Laboratory of Brain Homeostasis, Central South University, Changsha, China
| | - Dingquan Zou
- Department of Pain Management and Anesthesiology, The Second Xiangya Hospital, Central South University, Changsha, China
| | - Bo Hong
- Department of Pain Management and Anesthesiology, Yueyang Traditional Chinese Medicine Hospital, Yueyang, China
| | - Rong Hu
- Department of Pain, The Third Xiangya Hospital and Institute of Pain Medicine, Central South University, Changsha, China
| | - Tongbiao Yang
- Department of Pain, Yongzhou Central Hospital, Yongzhou, China
| | - Xinning Li
- Department of Pain Management and Anesthesiology, The Second Xiangya Hospital, Central South University, Changsha, China
| | - Xin Li
- Department of Pain Management and Anesthesiology, The Second Xiangya Hospital, Central South University, Changsha, China
| | - Junjiao Hu
- Department of Radiology, The Second Xiangya Hospital, Central South University, Changsha, China
| | - Ruixuan Wang
- Bourns Engineering, The University of California, Riverside, Riverside, California, USA
| | - Yaping Wang
- Department of Pain Management and Anesthesiology, The Second Xiangya Hospital, Central South University, Changsha, China
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Banat H, Ambrus R, Csóka I. Drug combinations for inhalation: Current products and future development addressing disease control and patient compliance. Int J Pharm 2023; 643:123070. [PMID: 37230369 DOI: 10.1016/j.ijpharm.2023.123070] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/12/2023] [Revised: 05/07/2023] [Accepted: 05/21/2023] [Indexed: 05/27/2023]
Abstract
Pulmonary delivery is an alternative route of administration with numerous advantages over conventional routes of administration. It provides low enzymatic exposure, fewer systemic side effects, no first-pass metabolism, and concentrated drug amounts at the site of the disease, making it an ideal route for the treatment of pulmonary diseases. Owing to the thin alveolar-capillary barrier, and large surface area that facilitates rapid absorption to the bloodstream in the lung, systemic delivery can be achieved as well. Administration of multiple drugs at one time became urgent to control chronic pulmonary diseases such as asthma and COPD, thus, development of drug combinations was proposed. Administration of medications with variable dosages from different inhalers leads to overburdening the patient and may cause low therapeutic intervention. Therefore, products that contain combined drugs to be delivered via a single inhaler have been developed to improve patient compliance, reduce different dose regimens, achieve higher disease control, and boost therapeutic effectiveness in some cases. This comprehensive review aimed to highlight the growth of drug combinations by inhalation over time, obstacles and challenges, and the possible progress to broaden the current options or to cover new indications in the future. Moreover, various pharmaceutical technologies in terms of formulation and device in correlation with inhaled combinations were discussed in this review. Hence, inhaled combination therapy is driven by the need to maintain and improve the quality of life for patients with chronic respiratory diseases; promoting drug combinations by inhalation to a higher level is a necessity.
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Affiliation(s)
- Heba Banat
- Institute of Pharmaceutical Technology and Regulatory Affairs, Faculty of Pharmacy, University of Szeged, Hungary
| | - Rita Ambrus
- Institute of Pharmaceutical Technology and Regulatory Affairs, Faculty of Pharmacy, University of Szeged, Hungary
| | - Ildikó Csóka
- Institute of Pharmaceutical Technology and Regulatory Affairs, Faculty of Pharmacy, University of Szeged, Hungary.
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Kukushliev VV, Sherman KA, Kurylo CM, Ortmann SD, Scheidt RA, Scheidt KB. Tapered Dose Postoperative Opioid Prescriptions Following Inpatient Total Hip and Knee Arthroplasty: Quality Improvement Study and Retrospective Review. J Arthroplasty 2023; 38:239-244. [PMID: 36075313 DOI: 10.1016/j.arth.2022.08.043] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/23/2022] [Revised: 08/26/2022] [Accepted: 08/27/2022] [Indexed: 02/03/2023] Open
Abstract
BACKGROUND Overprescription of pain medications directly fuels the opioid epidemic. Veterans are profoundly impacted. Tapered dose protocols may reduce excessive prescribing. METHODS A retrospective study of adult veterans who presented to our institution for primary total knee arthroplasty or total hip arthroplasty (THA) was performed. Postdischarge opioid use was reviewed before and after an opioid taper prescription protocol. The preprotocol and postprotocol groups had 299 and 89 veterans, respectively. Total Morphine Milligram Equivalent (MME) prescribed postdischarge, number of tablets prescribed, number of refills issued, 30-day emergency department visits, and 30-day readmissions were compared. Opioid naïve and chronic opioid users were both included. RESULTS Preprotocol and postprotocol implementation group, in combination with surgery type (total knee arthroplasty versus THA) and opioid naïve status, predicted MME. On average, the postprotocol group received 224 MME less, THA patients received 177 MME less, and nonopioid naïve patients received 152 MME more. CONCLUSION The opioid taper protocol led to less opioid administration after discharge. Taper protocols should be considered for postoperative pain management. LEVEL OF EVIDENCE III, retrospective comparison study.
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Affiliation(s)
- Vasil V Kukushliev
- Clement J. Zablocki VA Medical Center, Milwaukee, Wisconsin; Medical College of Wisconsin, Milwaukee, Wisconsin
| | | | - Christopher M Kurylo
- Clement J. Zablocki VA Medical Center, Milwaukee, Wisconsin; Medical College of Wisconsin, Milwaukee, Wisconsin
| | - Stephen D Ortmann
- Clement J. Zablocki VA Medical Center, Milwaukee, Wisconsin; Medical College of Wisconsin, Milwaukee, Wisconsin
| | - Robert A Scheidt
- Washington University in St. Louis School of Medicine, Saint Louis, Missouri
| | - Karl B Scheidt
- Clement J. Zablocki VA Medical Center, Milwaukee, Wisconsin; Medical College of Wisconsin, Milwaukee, Wisconsin
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Coracini CA, Zazula MF, Ferreira MO, da Silva JC, da Silva Scarton SR, Panis C, de Fátima Chasko Ribeiro L, da Silva Leal TS, Bertolini GRF. Acute effects of photobiomodulation applied on the dorsal root ganglion in gout model-induced rats. JOURNAL OF PHOTOCHEMISTRY AND PHOTOBIOLOGY. B, BIOLOGY 2023; 239:112644. [PMID: 36652793 DOI: 10.1016/j.jphotobiol.2022.112644] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/13/2022] [Accepted: 12/27/2022] [Indexed: 12/31/2022]
Abstract
Gouty arthritis is an inflammatory disease that triggers symptoms such as pain, swelling, and joint stiffness. Since its main therapy is medication, research on other forms of treatment that do not generate side effects is necessary. Given this, the objective of this research was to evaluate the effects of combined photobiomodulation (LASER and LED) applied on the dorsal root ganglion (DRG) in an experimental model of gouty arthritis. For this, 40 Wistar rats were randomized into 4 groups: simulation of the model with saline injection, without treatment (CTL; n = 10); gout simulation with photobiomodulation treatment (CTL-PBM; n = 10); gout model with the injection of monosodium urate crystals (1.25 mg) in the femorotibial joint, without treatment (GOT; n = 10); or gout model with photobiomodulation treatment (GOT-PBM; n = 10). After 7 h of gout induction, photobiomodulation was performed with a cluster of 4 diodes applied to the GRD region in animals from the CTL-PBM and GOT-PBM groups. After analysing the results, it was concluded that the therapy favored the reduction of edema and joint incapacity, as well as the increase in the nociceptive threshold and plantar grip strength. Furthermore, PBM stimulated an increase in the inflammatory response (with increased levels of IL-1β and greater recruitment of leukocytes) and greater activation of the antioxidant system. Therefore, PBM can be considered an effective therapeutic alternative to improve the functional status in this model of joint disease.
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Affiliation(s)
| | | | | | | | | | - Carolina Panis
- Universidade Estadual do Oeste do Paraná (UNIOESTE), Paraná, Brazil
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Guan Q, Velho RV, Sehouli J, Mechsner S. Endometriosis and Opioid Receptors: Are Opioids a Possible/Promising Treatment for Endometriosis? Int J Mol Sci 2023; 24:ijms24021633. [PMID: 36675147 PMCID: PMC9864914 DOI: 10.3390/ijms24021633] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/12/2022] [Revised: 01/04/2023] [Accepted: 01/10/2023] [Indexed: 01/17/2023] Open
Abstract
Endometriosis (EM), defined as the presence of endometrial-like tissue with surrounding smooth muscle cells outside the uterus, is a disregarded gynecological disease reported to affect 6-10% of women of reproductive age, with 30-50% of them suffering from chronic pelvic pain and infertility. Since the exact pathogenic mechanisms of EM are still unclear, no curative therapy is available. As pain is an important factor in EM, optimal analgesia should be sought, which to date has been treated primarily with non-steroidal anti-inflammatory drugs (NSAIDs), metamizole or, in extreme cases, opioids. Here, we review the pain therapy options, the mechanisms of pain development in EM, the endogenous opioid system and pain, as well as the opioid receptors and EM-associated pain. We also explore the drug abuse and addiction to opioids and the possible use of NOP receptors in terms of analgesia and improved tolerability as a target for EM-associated pain treatment. Emerging evidence has shown a promising functional profile of bifunctional NOP/MOP partial agonists as safe and nonaddictive analgesics. However, until now, the role of NOP receptors in EM has not been investigated. This review offers a thought which still needs further investigation but may provide potential options for relieving EM-associated pain.
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9
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Steigleman WA, Rose-Nussbaumer J, Al-Mohtaseb Z, Santhiago MR, Lin CC, Pantanelli SM, Kim SJ, Schallhorn JM. Management of Pain after Photorefractive Keratectomy: A Report by the American Academy of Ophthalmology. Ophthalmology 2023; 130:87-98. [PMID: 36207168 DOI: 10.1016/j.ophtha.2022.07.028] [Citation(s) in RCA: 11] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/22/2022] [Accepted: 07/26/2022] [Indexed: 11/21/2022] Open
Abstract
OBJECTIVE To evaluate current best practices for postoperative photorefractive keratectomy (PRK) pain control. METHODS Literature searches in the PubMed database were last conducted in October 2021 and were restricted to publications in English. This search identified 219 citations, of which 84 were reviewed in full text for their relevance to the scope of this assessment. Fifty-one articles met the criteria for inclusion; 16 studies were rated level I, 33 studies were rated level II, and 2 studies were rated level III. RESULTS Systemic opioid and nonsteroidal anti-inflammatory drugs (NSAIDs); topical NSAIDs; postoperative cold patches; bandage soft contact lenses (BCLs), notably senofilcon A contact lenses; and topical anesthetics were demonstrated to offer significantly better pain control than comparison treatments. Some other commonly reported pain mitigation interventions such as systemic gabapentinoids, chilled intraoperative balanced salt solution (BSS) irrigation, cycloplegia, and specific surface ablation technique strategies offered limited improvement in pain control over control treatments. CONCLUSIONS Systemic NSAIDs and opioid medications, topical NSAIDs, cold patches, BCLs, and topical anesthetics have been shown to provide improved pain control over alternative strategies and allow PRK-associated pain to be more tolerable for patients.
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Affiliation(s)
| | | | | | | | | | - Seth M Pantanelli
- Department of Ophthalmology, Penn State College of Medicine, Hershey, Pennsylvania
| | - Stephen J Kim
- Department of Ophthalmology, Vanderbilt University School of Medicine, Nashville, Tennessee
| | - Julie M Schallhorn
- Francis I. Proctor Foundation and Department of Ophthalmology, University of California, San Francisco, California
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Muacevic A, Adler JR, LeQuang JAK, Breve F, Magnusson P. Fixed Dose Versus Loose Dose: Analgesic Combinations. Cureus 2023; 15:e33320. [PMID: 36741676 PMCID: PMC9894647 DOI: 10.7759/cureus.33320] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/13/2022] [Accepted: 12/23/2022] [Indexed: 01/05/2023] Open
Abstract
Combinations of drugs may be fixed (two or more entities in a single product) or loose (two or more agents taken together but as individual agents) to help address multimechanistic pain. The use of opioids plus nonopioids can result in lower opioid consumption without sacrificing analgesic benefits. Drug combinations may offer additive or synergistic benefits. A variety of fixed-dose combination products are available on the market such as diclofenac plus thiocolchicoside, acetaminophen and caffeine, acetaminophen and opioid, ibuprofen and acetaminophen, tramadol and acetaminophen, and others. Fixed-dose combination products offer predictable pharmacokinetics and pharmacodynamics, known adverse events, and can reduce the pill burden. However, they are limited to certain drug combinations and doses; loose dosing allows prescribers the versatility to meet individual patient requirements as well as the ability to titrate as needed. Not all drug combinations offer synergistic benefits, which depend on the drugs and their doses. Certain drugs offer dual mechanisms of action in a single molecule, such as tapentadol, and these may further be used in combination with other analgesics. New technology allows for co-crystal productions of analgesic agents which may further improve drug characteristics, such as bioavailability. Combination analgesics are important additions to the analgesic armamentarium and may offer important benefits at lower doses than monotherapy.
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Su SH, Lai PF, Yu HY, Chen KC, Wu K, Huang CK, Tseng WC, Lai CY, Huang CP, Ho TJ. Application of acupuncture in the emergency department for patients with ileus: A pilot prospective cohort clinical study. Medicine (Baltimore) 2022; 101:e31245. [PMID: 36316877 PMCID: PMC9622632 DOI: 10.1097/md.0000000000031245] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/07/2022] Open
Abstract
Acupuncture can be conveniently used for pain control in patients with a variety of conditions, and it has obvious effects on various acute pains. In 2018, we implemented a program for emergency treatment with Chinese medicine to promote the integration of Chinese and Western medicine at the Emergency Department (ED). Ileus is a common cause of abdominal pain among patients in the ED, and it is an indication for emergency treatment with Chinese medicine. This study investigated the efficacy of acupuncture as a traditional Chinese medicine (TCM)-based treatment method for the treatment of patients with ileus in the ED. We analyzed data of patients with ileus, who visited ED between January and December 2019, and compared the length of ED stay between the Western medicine group and the Western medicine plus acupuncture group. Furthermore, pain intensity was measured by a visual analogue scale before and after acupuncture. We found that the length of ED stay was 10.8 hours lesser in the Western medicine plus acupuncture group than in the Western medicine group (P = .04), and the visual analogue scale score decreased by 2.0 on average from before to after acupuncture treatment (P = .02). Acupuncture treatment was effective and rapid in relieving the symptoms and discomfort in patients with ileus and in reducing their length of stay in the ED.
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Affiliation(s)
- San-Hua Su
- Department of Chinese Medicine, Hualien Tzu Chi Hospital, Hualien, Taiwan
- Integration Center of Traditional Chinese and Modern Medicine, Hualien Tzu Chi Hospital, Hualien, Taiwan
| | - Pei-Fang Lai
- Department of Emergency Medicine, Hualien Tzu Chi Hospital, Hualien, Taiwan
| | - Hsin-Yuan Yu
- Department of Chinese Medicine, Hualien Tzu Chi Hospital, Hualien, Taiwan
| | - Kun-Chuan Chen
- Department of Emergency Medicine, Hualien Tzu Chi Hospital, Hualien, Taiwan
| | - Kari Wu
- Department of Chinese Medicine, Hualien Tzu Chi Hospital, Hualien, Taiwan
| | - Chih-Kai Huang
- Department of Chinese Medicine, Hualien Tzu Chi Hospital, Hualien, Taiwan
| | - Wei-Chun Tseng
- Department of Chinese Medicine, Hualien Tzu Chi Hospital, Hualien, Taiwan
| | - Chun-Yu Lai
- Department of Chinese Medicine, Hualien Tzu Chi Hospital, Hualien, Taiwan
- Integration Center of Traditional Chinese and Modern Medicine, Hualien Tzu Chi Hospital, Hualien, Taiwan
| | - Chun-Ping Huang
- Integration Center of Traditional Chinese and Modern Medicine, Hualien Tzu Chi Hospital, Hualien, Taiwan
| | - Tsung-Jung Ho
- Department of Chinese Medicine, Hualien Tzu Chi Hospital, Hualien, Taiwan
- Integration Center of Traditional Chinese and Modern Medicine, Hualien Tzu Chi Hospital, Hualien, Taiwan
- School of Post-Baccalaureate Chinese Medicine, Tzu Chi University, Hualien, Taiwan
- * Correspondence: Tsung-Jung Ho, Department of Chinese Medicine, Integration Center of Traditional Chinese and Modern Medicine, Hualien Tzu Chi Hospital; School of Post-Baccalaureate Chinese Medicine, Tzu Chi University, Hualien, Taiwan, ROC Taiwan (e-mail: )
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12
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Belltall A, Zúñiga-Trejos S, Garrido-Cano I, Eroles P, Argente-Navarro MP, Buggy DJ, Díaz-Cambronero O, Mazzinari G. Solid Tumor Opioid Receptor Expression and Oncologic Outcomes: Analysis of the Cancer Genome Atlas and Genotype Tissue Expression Project. Front Oncol 2022; 12:801411. [PMID: 35359418 PMCID: PMC8960174 DOI: 10.3389/fonc.2022.801411] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/25/2021] [Accepted: 02/17/2022] [Indexed: 11/13/2022] Open
Abstract
Background Opioid receptors are expressed not only by neural cells in the central nervous system, but also by many solid tumor cancer cells. Whether perioperative opioids given for analgesia after tumor resection surgery might inadvertently activate tumor cells, promoting recurrence or metastasis, remains controversial. We analysed large public gene repositories of solid tumors to investigate differences in opioid receptor expression between normal and tumor tissues and their association with long-term oncologic outcomes. Methods We investigated the normalized gene expression of µ, κ, δ opioid receptors (MOR, KOR, DOR), Opioid Growth Factor (OGFR), and Toll-Like 4 (TLR4) receptors in normal and tumor samples from twelve solid tumor types. We carried out mixed multivariable logistic and Cox regression analysis on whether there was an association between these receptors' gene expression and the tissue where found, i.e., tumor or normal tissue. We also evaluated the association between tumor opioid receptor gene expression and patient disease-free interval (DFI) and overall survival (OS). Results We retrieved 8,780 tissue samples, 5,852 from tumor and 2,928 from normal tissue, of which 2,252 were from the Genotype Tissue Expression Project (GTEx) and 672 from the Cancer Genome Atlas (TCGA) repository. The Odds Ratio (OR) [95%CI] for gene expression of the specific opioid receptors in the examined tumors varied: MOR: 0.74 [0.63-0.87], KOR: 1.27 [1.17-1.37], DOR: 1.66 [1.48-1.87], TLR4: 0.29 [0.26-0.32], OGFR: 2.39 [2.05-2.78]. After controlling all confounding variables, including age and cancer stage, there was no association between tumor opioid receptor expression and long-term oncologic outcomes. Conclusion Opioid receptor gene expression varies between different solid tumor types. There was no association between tumor opioid receptor expression and recurrence. Understanding the significance of opioid receptor expression on tumor cells remains elusive.
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Affiliation(s)
- Amparo Belltall
- Perioperative Medicine Research Group, Instituto de Investigación Sanitaria la Fe, Valencia, Spain
- Departament de Anesthesiology, Hospital Universitari i Politécnic la Fe, Valencia, Spain
| | - Sheila Zúñiga-Trejos
- Bioinformatics and Biostatistics Unit, INCLIVA Biomedical Research Institute, Valencia, Spain
| | - Iris Garrido-Cano
- Breast Cancer Research Group, Molecular and Cellular Oncolgy Unit, Biomedical Research Institute, INCLIVA, Valencia, Spain
- Euro-Periscope: The Onco-Anaesthesiology Research Group (RG) of European Society of Anaesthesiology & Intensive Care (ESA-IC), Brussels, Belgium
| | - Pilar Eroles
- Breast Cancer Research Group, Molecular and Cellular Oncolgy Unit, Biomedical Research Institute, INCLIVA, Valencia, Spain
- Euro-Periscope: The Onco-Anaesthesiology Research Group (RG) of European Society of Anaesthesiology & Intensive Care (ESA-IC), Brussels, Belgium
| | - Maria Pilar Argente-Navarro
- Perioperative Medicine Research Group, Instituto de Investigación Sanitaria la Fe, Valencia, Spain
- Departament de Anesthesiology, Hospital Universitari i Politécnic la Fe, Valencia, Spain
| | - Donal J. Buggy
- Euro-Periscope: The Onco-Anaesthesiology Research Group (RG) of European Society of Anaesthesiology & Intensive Care (ESA-IC), Brussels, Belgium
- Department of Anaesthesiology and Perioperative Medicine, Mater University Hospital, University College Dublin, Dublin, Ireland
| | - Oscar Díaz-Cambronero
- Perioperative Medicine Research Group, Instituto de Investigación Sanitaria la Fe, Valencia, Spain
- Departament de Anesthesiology, Hospital Universitari i Politécnic la Fe, Valencia, Spain
- Euro-Periscope: The Onco-Anaesthesiology Research Group (RG) of European Society of Anaesthesiology & Intensive Care (ESA-IC), Brussels, Belgium
| | - Guido Mazzinari
- Perioperative Medicine Research Group, Instituto de Investigación Sanitaria la Fe, Valencia, Spain
- Departament de Anesthesiology, Hospital Universitari i Politécnic la Fe, Valencia, Spain
- Euro-Periscope: The Onco-Anaesthesiology Research Group (RG) of European Society of Anaesthesiology & Intensive Care (ESA-IC), Brussels, Belgium
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Chen MH, Chen Z, Zhao D. Impact of adding opioids to paravertebral blocks in breast cancer surgery patients: A systematic review and meta-analysis. World J Clin Cases 2022; 10:1852-1862. [PMID: 35317143 PMCID: PMC8891773 DOI: 10.12998/wjcc.v10.i6.1852] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/19/2021] [Revised: 10/21/2021] [Accepted: 01/19/2022] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Several breast cancer studies have reported the use of adjuvant opioids with the paravertebral block (PVB) to improve outcomes. However, there is no level-1 evidence justifying its use. AIM To elucidate if the addition of opioids to PVB improves pain control in breast cancer surgery patients. METHODS We conducted an electronic literature search across PubMed, Embase, Scopus, and Google Scholar databases up to October 20, 2020. Only randomized controlled trials (RCTs) comparing the addition of opioids to PVB with placebo for breast cancer surgery patients were included. RESULTS Six RCTs were included. Our meta-analysis indicated significantly reduced 24-h total analgesic consumption with the addition of opioids to PVB as compared to placebo [standardized mean difference (SMD) -1.57, 95% confidence interval (CI): -2.93, -0.21, I 2 = 94%]. However, on subgroup analysis, the results were non-significant for studies using single PVB (SMD: -1.76, 95%CI: -3.65, 0.13 I 2 = 95.09%) and studies using PVB infusion (SMD: -1.30, 95%CI: -4.26, 1.65, I 2 = 95.49%). Analysis of single PVB studies indicated no significant difference in the time to first analgesic request between opioid and placebo groups (mean difference -11.28, 95%CI: -42.00, 19.43, I 2 = 99.39%). Pain scores at 24 h were marginally lower in the opioid group (mean difference -1.10, 95%CI: -2.20, 0.00, I 2 = 0%). There was no difference in the incidence of postoperative nausea and vomiting between the two groups. CONCLUSION Current evidence suggests a limited role of adjuvant opioids with PVB for breast cancer surgery patients. Further homogenous RCTs with a large sample size are needed to clarify the beneficial role of opioids with PVB.
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Affiliation(s)
- Meng-Hua Chen
- Lanzhou University Medical College, Lanzhou 730000, Gansu Province, China
| | - Zheng Chen
- Department of Breast, Shandong Second Provincial General Hospital, Jinan 250021, Shandong Province, China
| | - Da Zhao
- Department of Oncology, The First Hospital of Lanzhou University, Lanzhou 730000, Gansu Province, China
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14
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Mattout HK, Fouda SM. The use of topical nalbuphine in different concentrations to control pain after photorefractive keratectomy. Int Ophthalmol 2022; 42:2145-2153. [PMID: 35020101 DOI: 10.1007/s10792-022-02214-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/22/2021] [Accepted: 01/01/2022] [Indexed: 10/19/2022]
Abstract
PURPOSE This is a randomized controlled study aiming to evaluate the safety and efficacy of two different concentrations of topical nalbuphine hydrochloride, when used to relieve pain in the first days following photorefractive keratectomy (PRK). METHODS This is a prospective double blinded randomized clinical trial that included 189 patients who had PRK for correction of low and moderate refractive errors. Patients were randomly assigned to three groups according to the eye drops given to relieve pain in the first three postoperative days; the first group received topical nalbuphine with a concentration of 2 mg/ml (Group A = 64 patients), the second group received topical nalbuphine in a concentration of 1 mg/ml (Group B = 69 patients) and the third group received topical artificial tears only (Group C = 56 patients).The patients were asked to rate their pain daily using a numeric rating scale and to record the number of drops instillation times/day. The time needed for complete epithelial healing, best-corrected visual acuity (BCVA) and spherical equivalent after three months were recorded in each group. RESULTS In the first three days, there was a statistically significant difference in pain score among the three groups with lower values in the two topical nalbuphine groups when compared with the control group receiving artificial tears. Moreover, the higher concentration group showed significantly lower pain score and less number of drops used /day in comparison with the lower concentration group.There were no statistically significant differences in epithelial healing time, BCVA and spherical equivalent after three months among the three groups. CONCLUSION The use of topical nalbuphine is effective in relieving pain in the first few days following PRK and this pain relief is not associated with any compromise regarding epithelial healing nor refractive outcome. The pain control with 2 mg/ml concentration is significantly higher than that with 1 mg/ml concentration of nalbuphine. Trial registration numberISRCTN21394752 https://doi.org/10.1186/ISRCTN21394752 The trial is retrospectively registered in ISRCTN registry at March 08, 2021.
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Affiliation(s)
- Hala Kamal Mattout
- Ophthalmology Department, Faculty of Medicine, Zagazig University, Zagazig, Egypt.
| | - Sameh Mosaad Fouda
- Ophthalmology Department, Faculty of Medicine, Zagazig University, Zagazig, Egypt
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15
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Wang F, Li H, Mu Q, Shan L, Kang Y, Yang S, Chang HC, Su KP, Liu Y. Association of Acute Postoperative Pain and Cigarette Smoking With Cerebrospinal Fluid Levels of Beta-Endorphin and Substance P. Front Mol Neurosci 2022; 14:755799. [PMID: 35177964 PMCID: PMC8845024 DOI: 10.3389/fnmol.2021.755799] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/09/2021] [Accepted: 12/16/2021] [Indexed: 11/25/2022] Open
Abstract
Objectives: Cigarette smoking is associated with postoperative pain perception, which might be mediated by beta-endorphin and substance P. These effects on postoperative pain perception have never been investigated in human cerebrospinal fluid (CSF), which reflects biochemical alterations in the brain. Therefore, we investigated the associations among cigarette smoking, postoperative pain, and levels of beta-endorphin and substance P in human CSF. Methods: We recruited 160 Chinese men (80 active smokers and 80 nonsmokers) who underwent lumbar puncture before anterior cruciate ligament reconstruction, and 5-ml CSF samples were collected. Pain visual analog scale (VAS) scores, post-anesthetic recovery duration (PARD), and smoking variables were obtained. CSF levels of beta-endorphin and substance P were measured. Results: Compared to non-smokers, active smokers had significantly higher pain VAS (2.40 ± 0.67 vs. 1.70 ± 0.86, p < 0.001) and PARD scores (9.13 ± 2.11 vs. 7.27 ± 1.35, p = 0.001), lower CSF beta-endorphin (33.76 ± 1.77 vs. 35.66 ± 2.20, p = 0.001) and higher CSF substance P (2,124.46 ± 217.34 vs. 1,817.65 ± 302.14, p < 0.001) levels. Pain VAS scores correlated with PARD in active smokers (r = 0.443, p = 0.001). Conclusions: Cigarette smoking is associated with increased postoperative pain intensity, shown by delayed pain perception, higher pain VAS scores, and lower beta-endorphin and higher substance P levels in the CSF of active smokers. The more extended postoperative pain perception is delayed, the more pain intensity increases.
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Affiliation(s)
- Fan Wang
- Beijing Hui-Long-Guan Hospital, Peking University, Beijing, China
- Key Laboratory of Psychosomatic Medicine, Inner Mongolia Medical University, Huhhot, China
| | - Hui Li
- Department of Biomedical Engineering, College of Engineering, Peking University, Beijing, China
- Xinjiang Key Laboratory of Neurological Disorder Research, The Second Affiliated Hospital of Xinjiang Medical University, Urumqi, China
| | - Qingshuang Mu
- Xinjiang Key Laboratory of Neurological Disorder Research, The Second Affiliated Hospital of Xinjiang Medical University, Urumqi, China
| | - Ligang Shan
- Key Laboratory of Psychosomatic Medicine, Inner Mongolia Medical University, Huhhot, China
- Department of Anesthesiology, The Second Affiliated Hospital of Xiamen Medical College, Xiamen, China
| | - Yimin Kang
- Key Laboratory of Psychosomatic Medicine, Inner Mongolia Medical University, Huhhot, China
- Department of Anesthesiology, The Affiliated Hospital of Inner Mongolia Medical University, Huhhot, China
| | - Shizhuo Yang
- School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, China
| | - Hui-Chih Chang
- Department of Psychiatry & Mind-Body Interface Laboratory (MBI-Lab), China Medical University Hospital, Taichung, Taiwan
- College of Medicine, China Medical University, Taichung, Taiwan
| | - Kuan-Pin Su
- Department of Psychiatry & Mind-Body Interface Laboratory (MBI-Lab), China Medical University Hospital, Taichung, Taiwan
- College of Medicine, China Medical University, Taichung, Taiwan
- An-Nan Hospital, China Medical University, Tainan, Taiwan
| | - Yanlong Liu
- The Affiliated Kangning Hospital, Wenzhou Medical University, Wenzhou, China
- School of Mental Health, Wenzhou Medical University, Wenzhou, China
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16
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Gutierrez Y, Pourali SP, Kucharik AH, Jones ME, Rajkumar JR, Armstrong AW. Topical opioid use in dermatologic disease: A systematic review. Dermatol Ther 2021; 34:e15150. [PMID: 34605133 DOI: 10.1111/dth.15150] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/14/2021] [Revised: 09/14/2021] [Accepted: 09/30/2021] [Indexed: 01/12/2023]
Abstract
Topical opioid formulations offer a potential solution to manage pain and decrease the use of systemic opioids. Synthesis of use and efficacy of topical opioids in dermatological conditions has not been well characterized. We conducted a systematic search of the PubMed, Embase, and Cochrane databases from 1980 to February 2021. This study analyzed data from 14 articles and 263 patients on the use of topical opioids for pain related to chronic ulcers, burns, oral lichen planus, photodynamic therapy, and split-thickness skin grafts. Topical opioids included in this review were topical morphine and diamorphine. Common formulations consisted of 0.2-10 mg of opioid compounded with hydrogel or IntraSite gel. Topical opioids were variably effective in the use for pain control related to chronic ulcers and other dermatologic conditions. For example, the use of topical opioids appears to be effective in the reduction of pain related to pressure ulcers. Topical opioids were generally well tolerated. Insufficient data exist to adequately evaluate the efficacy and safety of topical opioid use in the context of nonpressure ulcers, burns, oral lichen planus, photodynamic therapy, and split-thickness skin grafts.
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Affiliation(s)
- Yasmin Gutierrez
- School of Medicine, University of California Riverside, Riverside, California, USA
| | - Sarah P Pourali
- School of Medicine, Vanderbilt University, Nashville, Tennessee, USA
| | - Alison H Kucharik
- Charles E. Schmidt College of Medicine, Florida Atlantic University, Boca Raton, Florida, USA
| | - Madison E Jones
- Keck School of Medicine, University of Southern California, Los Angeles, California, USA
| | - Jeffrey R Rajkumar
- College of Medicine at Chicago, University of Illinois, Chicago, Illinois, USA
| | - April W Armstrong
- Keck School of Medicine, University of Southern California, Los Angeles, California, USA
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17
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Zhao G, Shi Y, Gong C, Liu T, Nan W, Ma L, Wu Z, Da C, Zhou K, Zhang H. Curcumin Exerts Antinociceptive Effects in Cancer-Induced Bone Pain via an Endogenous Opioid Mechanism. Front Neurosci 2021; 15:696861. [PMID: 34539332 PMCID: PMC8446608 DOI: 10.3389/fnins.2021.696861] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/18/2021] [Accepted: 07/12/2021] [Indexed: 11/13/2022] Open
Abstract
Cancer pain is one of the main complications in advanced cancer patients, and its management is still challenging. Therefore, there is an urgent need to develop novel pharmacotherapy for cancer pain. Several natural products have attracted the interest of researchers. In previous studies, curcumin has proved to exhibit antitumor, antiviral, antioxidant, anti-inflammatory, and analgesic effects. However, the analgesic mechanism of curcumin has not been elucidated. Thus, in this study, we aimed to elucidate the antinociceptive potency and analgesic mechanism of curcumin in cancer-induced bone pain. Our results showed that consecutive curcumin treatment (30, 60, 120 mg/kg, i.p., twice daily for 11 days) produced significant analgesic activity, but had no effect on the progress of the bone cancer pain. Notably, pretreatment with naloxone, a non-selective opioid receptor antagonist, markedly reversed the antinociceptive effect induced by curcumin. Moreover, in primary cultured rat dorsal root ganglion (DRG) neurons, curcumin significantly up-regulated the expression of proopiomelanocortin (Pomc) and promoted the release of β-endorphin and enkephalin. Furthermore, pretreatment with the antiserum of β-endorphin or enkephalin markedly attenuated curcumin-induced analgesia in cancer-induced bone pain. Our present study, for the first time, showed that curcumin attenuates cancer-induced bone pain. The results also suggested that stimulation of expression of DRG neurons β-endorphin and enkephalin mediates the antinociceptive effect of curcumin in pain hypersensitivity conditions.
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Affiliation(s)
- Guanghai Zhao
- Department of Orthopedics, Lanzhou University Second Hospital, Lanzhou, China.,The Second Clinical Medical College, Lanzhou University, Lanzhou, China.,Orthopaedics Key Laboratory of Gansu Province, Lanzhou University, Lanzhou, China
| | - Yongqiang Shi
- Department of Orthopedics, Lanzhou University Second Hospital, Lanzhou, China.,The Second Clinical Medical College, Lanzhou University, Lanzhou, China.,Orthopaedics Key Laboratory of Gansu Province, Lanzhou University, Lanzhou, China
| | - Chaoyang Gong
- Department of Orthopedics, Lanzhou University Second Hospital, Lanzhou, China.,The Second Clinical Medical College, Lanzhou University, Lanzhou, China.,Orthopaedics Key Laboratory of Gansu Province, Lanzhou University, Lanzhou, China
| | - Taicong Liu
- Department of Orthopedics, Lanzhou University Second Hospital, Lanzhou, China.,The Second Clinical Medical College, Lanzhou University, Lanzhou, China.,Orthopaedics Key Laboratory of Gansu Province, Lanzhou University, Lanzhou, China
| | - Wei Nan
- Department of Orthopedics, Lanzhou University Second Hospital, Lanzhou, China
| | - Lin Ma
- Department of Orthopedics, Lanzhou University Second Hospital, Lanzhou, China.,The Second Clinical Medical College, Lanzhou University, Lanzhou, China.,Orthopaedics Key Laboratory of Gansu Province, Lanzhou University, Lanzhou, China
| | - Zuolong Wu
- Department of Orthopedics, Lanzhou University Second Hospital, Lanzhou, China.,The Second Clinical Medical College, Lanzhou University, Lanzhou, China.,Orthopaedics Key Laboratory of Gansu Province, Lanzhou University, Lanzhou, China
| | - Chaoming Da
- Department of Orthopedics, Lanzhou University Second Hospital, Lanzhou, China.,The Second Clinical Medical College, Lanzhou University, Lanzhou, China.,Orthopaedics Key Laboratory of Gansu Province, Lanzhou University, Lanzhou, China
| | - Kaisheng Zhou
- Department of Orthopedics, Lanzhou University Second Hospital, Lanzhou, China
| | - Haihong Zhang
- Department of Orthopedics, Lanzhou University Second Hospital, Lanzhou, China.,The Second Clinical Medical College, Lanzhou University, Lanzhou, China.,Orthopaedics Key Laboratory of Gansu Province, Lanzhou University, Lanzhou, China
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18
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Katagiri H, Nakamura K, Muneta T, Watanabe T, Miyatake K, Sekiya I, Koga H, Tsuji K. Inflammatory and healing environment in synovial fluid after anterior cruciate ligament reconstruction: Granulocytes and endogenous opioids as new targets of postoperative pain. Biochem Biophys Rep 2021; 26:100981. [PMID: 33997313 PMCID: PMC8093890 DOI: 10.1016/j.bbrep.2021.100981] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/26/2019] [Revised: 12/30/2020] [Accepted: 03/08/2021] [Indexed: 11/18/2022] Open
Abstract
Background Biological processes after anterior cruciate ligament reconstruction (ACLR) is crucial for recovery. However, alterations in the of synovial fluid cell population during the acute phase following ACLR and the relationship between these cells and postoperative pain is unclear. The goal of this study was to reveal alterations in synovial fluid cell population during the acute phase following ACLR and relationship between postoperative pain and proportion of synovial fluid cells. Methods Synovial fluids were obtained from all patients (n = 50) before surgery and from patients who showed hydrarthrosis at days 4 (n = 25), and 21 (n = 42) post-surgery. The cell population was analyzed by flow cytometry. IL1β, IL8, and met-enkephalin in synovial fluid were quantitated by enzyme-linked immunosorbent assay. Patients answered numerical rating scale (NRS) questionnaire at 4 days and approximately 4 weeks postoperatively. Results The granulocyte population was significantly higher at 4 days after surgery than at any other time points. The population of macrophages was 3.2 times and 7.7 times as high as at surgery on days 4 and 21, respectively. T cell population was significantly higher 21 days after surgery compared to 4 days after surgery. All NRS 4 weeks after surgery showed a significant negative correlation with the granulocyte population in synovial fluid 4 days after surgery. Granulocyte population in synovial fluid significantly correlated with the levels of IL1β and IL8. Postoperative pain at rest tended to decrease with an increase in met-enkephalin concentration 4 days after ACLR. Conclusions Synovial fluid after ACLR had an inflammatory environment at early time points and a healing environment in the subsequent phase about concerning to the cellular composition. A proportion of synovial fluid cells and endogenous opioids affected postoperative pain.
Granulocyte population was higher at 4 days after ACLR than at other time points. Postoperative pain negatively correlated with the granulocyte in synovial fluid. Granulocyte population in synovial fluid correlate with IL1β and IL8 concentration. Postoperative pain tended to decrease with an increase in met-enkephalin.
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Affiliation(s)
- Hiroki Katagiri
- Department of Joint Surgery and Sports Medicine, Tokyo Medical and Dental University, Japan
| | - Kaori Nakamura
- Department of Joint Surgery and Sports Medicine, Tokyo Medical and Dental University, Japan
| | - Takeshi Muneta
- Department of Joint Surgery and Sports Medicine, Tokyo Medical and Dental University, Japan
| | - Toshifumi Watanabe
- Department of Joint Surgery and Sports Medicine, Tokyo Medical and Dental University, Japan
| | - Kazumasa Miyatake
- Department of Joint Surgery and Sports Medicine, Tokyo Medical and Dental University, Japan
| | - Ichiro Sekiya
- Center for Stem Cell and Regenerative Medicine, Tokyo Medical and Dental University, Japan
| | - Hideyuki Koga
- Department of Joint Surgery and Sports Medicine, Tokyo Medical and Dental University, Japan
| | - Kunikazu Tsuji
- Department of Cartilage Regeneration, Tokyo Medical and Dental University, Japan
- Corresponding author. Tokyo Medical and Dental University, Department of Cartilage Regeneration, 1-5-45 Yushima, Bunkyo-ku, Tokyo, 113-8510, Japan.
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19
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Abstract
Opioids form an important component of general anesthesia and perioperative analgesia. Discharge opioid prescriptions are identified as a contributor for persistent opioid use and diversion. In parallel, there is increased enthusiasm to advocate opioid-free strategies, which include a combination of known analgesics and adjuvants, many of which are in the form of continuous infusions. This article critically reviews perioperative opioid use, especially in view of opioid-sparing versus opioid-free strategies. The data indicate that opioid-free strategies, however noble in their cause, do not fully acknowledge the limitations and gaps within the existing evidence and clinical practice considerations. Moreover, they do not allow analgesic titration based on patient needs; are unclear about optimal components and their role in different surgical settings and perioperative phases; and do not serve to decrease the risk of persistent opioid use, thereby distracting us from optimizing pain and minimizing realistic long-term harms.
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20
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Abstract
PURPOSE OF REVIEW With this review, we aimed to investigate the effect of exercise on migraine and explored the possibility of exercise as a treatment option for migraine. RECENT FINDINGS A close association of physical activity and exercise with migraine has been reported in clinical and population-based studies. Recent randomized controlled trials investigating the effect of aerobic exercise as a migraine-preventive treatment have revealed a notable improvement in migraine symptoms. Data on the effect of anaerobic exercise and exercise for flexibility, coordination, and relaxation on migraine are currently insufficient to make any recommendations. Possible pathways for the attenuation of migraine by exercise include the endogenous opioid and cannabinoid systems, brain-derived neurotrophic factor, inflammation, and behavioral/psychological factors. Regarding efficacy, side effects, and health benefits, aerobic exercise is a potentially beneficial strategy in the preventive treatment of migraine. Further studies are needed to delineate an evidence-based exercise program for migraine treatment.
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21
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Zhou X, Cao SG, Tan XJ, Liu XD, Li ZQ, Kong LX, Tian YL, Liu D, Shen S, Sun YQ, Jiang HT, Zhou YB. Effects of Transcutaneous Electrical Acupoint Stimulation (TEAS) on Postoperative Recovery in Patients with Gastric Cancer: A Randomized Controlled Trial. Cancer Manag Res 2021; 13:1449-1458. [PMID: 33603487 PMCID: PMC7886100 DOI: 10.2147/cmar.s292325] [Citation(s) in RCA: 31] [Impact Index Per Article: 7.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/17/2020] [Accepted: 01/14/2021] [Indexed: 01/18/2023] Open
Abstract
Purpose Transcutaneous electrical acupoint stimulation (TEAS) is an innovative choice for postoperative pain management. However, the safety and effectiveness of this traditional Chinese medicine (TCM) therapy for patients who underwent gastrectomy is largely unknown. So, the purpose of this study is to evaluate the safety and effectiveness of TEAS for patients who underwent gastrectomy. Patients and Methods We recruited 96 patients with gastric cancer from May 2019 to November 2019; 82 patients were enrolled, and 81 patients completed. Patients were randomly assigned to TEAS group (TG) received TEAS on postoperative day (POD) 1–3 or control group (CG) at a 1:1 ratio. The primary outcomes were pain score and consumption of analgesics. The secondary were the time of first postoperative flatus and defecation, frequency of postoperative nausea, vomiting, distention, diarrhea, comfort of semi-fluid diet, Clavien-Dindo grade (C-D grade) and length of postoperative day. We performed hematological analysis to explore the possible mechanisms. Results Overall, 81 patients were enrolled included in the analysis. Compared with CG, pain scores in TG were lower on POD 1–5 (average: 2.55±0.21 vs 3.10±0.42, P<0.001), and the use rate of opioids was lower (43.9 vs 75.0, P=0.004); time of first postoperative flatus (55.63±16.74 vs 72.60±20.92, P<0.001) and defecation (72.20±16.24 vs 95.78±17.75, P<0.001) were shorter; the frequency of nausea were fewer (1.88±1.09 vs 2.58±0.77, P=0.029) and patients were more comfortable with semi-fluid diet (7.63±0.63 vs 6.93±0.69, P<0.001); among the hematologic results, β-endorphin (β-End), interleukin-2 (IL-2), motilin (MTL) on POD 3, POD 5 were lower, 5-hydroxytryptamine (5-HT), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α) were higher. And no adverse event was reported. Conclusion TEAS can relieve postoperative pain and promote the recovery of gastrointestinal function. Consequently, it can be an adjunctive therapy to enhance postoperative recovery for patients after gastrectomy.
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Affiliation(s)
- Xin Zhou
- Department of Gastrointestinal Surgery, The Affiliated Hospital of Qingdao University, Qingdao, Shandong Province, People's Republic of China
| | - Shou-Gen Cao
- Department of Gastrointestinal Surgery, The Affiliated Hospital of Qingdao University, Qingdao, Shandong Province, People's Republic of China
| | - Xiao-Jie Tan
- Department of Gastrointestinal Surgery, The Affiliated Hospital of Qingdao University, Qingdao, Shandong Province, People's Republic of China
| | - Xiao-Dong Liu
- Department of Gastrointestinal Surgery, The Affiliated Hospital of Qingdao University, Qingdao, Shandong Province, People's Republic of China
| | - Ze-Qun Li
- Department of Gastrointestinal Surgery, The Affiliated Hospital of Qingdao University, Qingdao, Shandong Province, People's Republic of China
| | - Ling-Xin Kong
- Department of Rehabilitation, The Affiliated Hospital of Qingdao University, Qingdao, Shandong Province, People's Republic of China
| | - Yu-Long Tian
- Department of Gastrointestinal Surgery, The Affiliated Hospital of Qingdao University, Qingdao, Shandong Province, People's Republic of China
| | - Dan Liu
- Department of Gastrointestinal Surgery, The Affiliated Hospital of Qingdao University, Qingdao, Shandong Province, People's Republic of China
| | - Shuai Shen
- Department of Gastrointestinal Surgery, The Affiliated Hospital of Qingdao University, Qingdao, Shandong Province, People's Republic of China
| | - Yu-Qi Sun
- Department of Gastrointestinal Surgery, The Affiliated Hospital of Qingdao University, Qingdao, Shandong Province, People's Republic of China
| | - Hai-Tao Jiang
- Department of Gastrointestinal Surgery, The Affiliated Hospital of Qingdao University, Qingdao, Shandong Province, People's Republic of China
| | - Yan-Bing Zhou
- Department of Gastrointestinal Surgery, The Affiliated Hospital of Qingdao University, Qingdao, Shandong Province, People's Republic of China
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22
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Trento MMS, Moré AOO, Duarte ECW, Martins DF. Peripheral receptors and neuromediators involved in the antihyperalgesic effects of acupuncture: a state-of-the-art review. Pflugers Arch 2021; 473:573-593. [PMID: 33474636 DOI: 10.1007/s00424-020-02503-0] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/19/2020] [Revised: 11/23/2020] [Accepted: 12/03/2020] [Indexed: 12/30/2022]
Abstract
The present study aims to describe state-of-the-art of preclinical studies that have investigated peripheral receptors and neuromediators involved in the antihyperalgesic effects of acupuncture. The PubMed, Scopus, and Web of Science databases were searched using the integrative review method. Preclinical articles that involved the study of peripheral receptors and neuromediators on the pain control effects of acupuncture in rats or mice were selected using a predefined search strategy. From this search, 456 articles were found, and 29 of them met the inclusion criteria of the study. The selected articles addressed the following peripheral receptors: opioid (n = 9), adenosine (n = 5), cannabinoid (n = 5), transient receptor potential vanilloid (TRPV) (n = 3), histamine (n = 2), adrenergic (n = 1), muscarinic (n = 1), corticotrophin-releasing factor (CRF) (n = 2), IL-1 (n = 1), and endothelin (n = 1) receptors. The peripheral neuromediators correlated with the peripheral pain control effect were as follows: opioid peptides (n = 4), adenosine (n = 3), histamine (n = 1), substance P (n = 1) calcitonin gene-related peptide (CGRP) (n = 1), anandamide (n = 1), nitric oxide (n = 1), and norepinephrine (n = 1). This review summarizes the methods used to investigate the peripheral effects of acupuncture and discusses the main findings on each family of receptors and neuromediators. Ten families of peripheral receptors and 8 types of neuromediators were correlated with the antihyperalgesic effects of acupuncture in preclinical studies. Considering the benefits of a better understanding of the role of peripheral receptors and neuromediators in the context pain management, the findings of the present study highlight the importance of deepening the exploration of the peripheral mechanisms of acupuncture.
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Affiliation(s)
| | - Ari Ojeda Ocampo Moré
- Integrative Medicine and Acupuncture Service, University Hospital, Federal University of Santa Catarina, R. Profa. Maria Flora Pausewang, s/n - Trindade, Florianópolis, Santa Catalina, CEP: 88036-800, Brazil.
| | | | - Daniel Fernandes Martins
- Postgraduate Program in Health Sciences, University of Southern Santa Catarina, Palhoça, Santa Catarina, Brazil.,Experimental Neuroscience Laboratory (LaNEx), University of Southern Santa Catarina, Palhoça, Santa Catarina, Brazil
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23
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Bagade S, Joshi S, Punamiya S, Malliwal A, Naik C, Ansari A. To evaluate the efficacy of buprenorphine and 2% lignocaine with adrenaline as postoperative analgesia following mandibular third molar surgery: A comparative study. Ann Maxillofac Surg 2021; 11:236-240. [PMID: 35265491 PMCID: PMC8848719 DOI: 10.4103/ams.ams_416_20] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/03/2020] [Revised: 08/24/2021] [Accepted: 09/21/2021] [Indexed: 11/24/2022] Open
Abstract
Introduction: Opioid analgesics have an advantage over nonsteroidal anti-inflammatory drugs in that they do not cause direct organ damage. Buprenorphine has an antinociceptive potency approximately 25–50 times greater than that of morphine. Hence, in this study, buprenorphine was added to local anaesthesia in relieving postoperative pain after lower third molar surgery when given as inferior alveolar nerve block. The aim of this study was to evaluate the efficacy of buprenorphine in managing postoperative pain after lower third molar surgery. Materials and Methods: Fifty patients requiring lower third molar surgery were randomly divided into two groups. Group A received buprenorphine added to 2% lignocaine with 1:80,000 adrenaline and Group B received 2% lignocaine with 1:80,000 adrenaline. Parameters assessed were onset of anaesthesia, depth of anaesthesia, intraoperative monitoring of adverse effects, duration of analgesia, and number of analgesics consumed. Statistical analysis was carried out using SPSS software version 21. The data were compared using Student's t-test. The level of significance was set at 0.05. Results: There was a significant difference in onset of anaesthesia between Group A and Group B (P < 0.05). Depth of anaesthesia and duration of analgesia were greater in Group A (56 h 36 min) than Group B (3 h 24 min). Analgesics consumed by Group A (0.9) were significantly less compared to Group B (9.2) and it was highly significant (P = 0.000). Discussion: Buprenorphine when added to local anaesthesia can prolong postoperative analgesia with minimum or no side effects. Hence, buprenorphine can be safely used for lower third molar surgery.
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24
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Kan T, Yoshikawa M, Watanabe M, Miura M, Ito K, Matsuda M, Iwao K, Kobayashi H, Suzuki T, Suzuki T. Sialorphin Potentiates Effects of [Met 5]Enkephalin without Toxicity by Action other than Peptidase Inhibition. J Pharmacol Exp Ther 2020; 375:104-114. [PMID: 32759368 DOI: 10.1124/jpet.120.266080] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/02/2020] [Accepted: 07/28/2020] [Indexed: 11/22/2022] Open
Abstract
This dose-response study investigated the effects of sialorphin on [Met5]enkephalin (ME)-induced inhibition of contractions in mouse vas deferens and antinociception in male rats. Differences were compared among combinations of three chemical peptidase inhibitors: amastatin, captopril, and phosphoramidon. The ratio of potencies of ME in mouse vas deferens pretreated with both sialorphin (100 µM) and a mixture of the three peptidase inhibitors (1 µM each) was higher than that with the mixture of peptidase inhibitors alone at any dose. Intrathecal administration of sialorphin (100-400 nmol) significantly and dose dependently increased ME (3 nmol)-induced antinociception with the mixture of three peptidase inhibitors (10 nmol each). The degree of antinociception with a combination of any two of the peptidase inhibitors (10 nmol each) in the absence of sialorphin was less than that in the presence of sialorphin (200 nmol). Pretreatment with both sialorphin (200 nmol) and the mixture of three peptidase inhibitors (10 nmol each) produced an approximately 100-fold augmentation in ME (10 nmol)-induced antinociception, but without signs of toxicity such as motor dysfunction in rats. Radioligand receptor binding assay revealed that sialorphin did not affect either binding affinity or maximal binding capacity of [d-Ala2,N-MePhe4,Gly-ol5]enkephalin. These results indicate that sialorphin potentiates the effects of ME without toxicity by a mechanism other than peptidase inhibition and with no effect on its affinity to µ-opioid receptors. SIGNIFICANCE STATEMENT: Sialorphin is regarded as an endogenous peptidase inhibitor that interacts with enkephalin-degrading enzymes. The results of these in vitro and in vivo studies confirm that sialorphin potentiates the effects of [Met5]enkephalin without toxicity by an action other than peptidase inhibition. This suggests that sialorphin offers the advantage of reducing or negating the side effects of opioid drugs and endogenous opioid peptides.
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Affiliation(s)
- Takugi Kan
- Departments of Anesthesiology (T.K., M.W., M.Mi., K.I., M.Ma., Ta.S., To.S.) and Clinical Pharmacology (M.Y., H.K.) and Education and Research Support Center (K.I.), Tokai University School of Medicine, Kanagawa, Japan
| | - Masanobu Yoshikawa
- Departments of Anesthesiology (T.K., M.W., M.Mi., K.I., M.Ma., Ta.S., To.S.) and Clinical Pharmacology (M.Y., H.K.) and Education and Research Support Center (K.I.), Tokai University School of Medicine, Kanagawa, Japan
| | - Mariko Watanabe
- Departments of Anesthesiology (T.K., M.W., M.Mi., K.I., M.Ma., Ta.S., To.S.) and Clinical Pharmacology (M.Y., H.K.) and Education and Research Support Center (K.I.), Tokai University School of Medicine, Kanagawa, Japan
| | - Masaaki Miura
- Departments of Anesthesiology (T.K., M.W., M.Mi., K.I., M.Ma., Ta.S., To.S.) and Clinical Pharmacology (M.Y., H.K.) and Education and Research Support Center (K.I.), Tokai University School of Medicine, Kanagawa, Japan
| | - Kenji Ito
- Departments of Anesthesiology (T.K., M.W., M.Mi., K.I., M.Ma., Ta.S., To.S.) and Clinical Pharmacology (M.Y., H.K.) and Education and Research Support Center (K.I.), Tokai University School of Medicine, Kanagawa, Japan
| | - Mitsumasa Matsuda
- Departments of Anesthesiology (T.K., M.W., M.Mi., K.I., M.Ma., Ta.S., To.S.) and Clinical Pharmacology (M.Y., H.K.) and Education and Research Support Center (K.I.), Tokai University School of Medicine, Kanagawa, Japan
| | - Kayoko Iwao
- Departments of Anesthesiology (T.K., M.W., M.Mi., K.I., M.Ma., Ta.S., To.S.) and Clinical Pharmacology (M.Y., H.K.) and Education and Research Support Center (K.I.), Tokai University School of Medicine, Kanagawa, Japan
| | - Hiroyuki Kobayashi
- Departments of Anesthesiology (T.K., M.W., M.Mi., K.I., M.Ma., Ta.S., To.S.) and Clinical Pharmacology (M.Y., H.K.) and Education and Research Support Center (K.I.), Tokai University School of Medicine, Kanagawa, Japan
| | - Takeshi Suzuki
- Departments of Anesthesiology (T.K., M.W., M.Mi., K.I., M.Ma., Ta.S., To.S.) and Clinical Pharmacology (M.Y., H.K.) and Education and Research Support Center (K.I.), Tokai University School of Medicine, Kanagawa, Japan
| | - Toshiyasu Suzuki
- Departments of Anesthesiology (T.K., M.W., M.Mi., K.I., M.Ma., Ta.S., To.S.) and Clinical Pharmacology (M.Y., H.K.) and Education and Research Support Center (K.I.), Tokai University School of Medicine, Kanagawa, Japan
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25
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Ahmed F, Tscharke B, O'Brien JW, Cabot PJ, Hall WD, Mueller JF, Thomas KV. Can wastewater analysis be used as a tool to assess the burden of pain treatment within a population? ENVIRONMENTAL RESEARCH 2020; 188:109769. [PMID: 32535354 DOI: 10.1016/j.envres.2020.109769] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/18/2020] [Revised: 05/30/2020] [Accepted: 05/30/2020] [Indexed: 06/11/2023]
Abstract
Pain is a global health priority that is challenging to asses. Here we propose a new approach to estimating the burden of pain treatment in a population using wastewater-based epidemiology (WBE). WBE is able to quantify multiple pharmaceutical compounds in order to estimate consumption by a population. Wastewater samples collected from areas representing whole communities can be analysed to estimate the consumption of drugs used to treat pain, such as nonsteroidal anti-inflammatory drugs (NSAIDs) and opioids. The collection and analysis of wastewater can be conducted systematically to estimate the total consumption of NSAIDs and/or opioids in the population of a catchment area and to compare changes over time within the catchment or between different catchment populations. Consumption estimates can be combined by standardising the mass consumed to Defined Daily Doses (DDD) or morphine equivalents in order to assess, the population burden of pain treatment from mild to moderate (for NSAIDs) and for strong and severe pain (for opioids). We propose this method could be used to evaluate the total pain treatment burden between locations and over time. While this concept shows promise, future studies should evaluate the applicability as a tool to measure the burden of pain receiving treatment in a community.
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Affiliation(s)
- Fahad Ahmed
- Queensland Alliance for Environmental Health Sciences (QAEHS), The University of Queensland, Woolloongabba, QLD, 4102, Australia.
| | - Benjamin Tscharke
- Queensland Alliance for Environmental Health Sciences (QAEHS), The University of Queensland, Woolloongabba, QLD, 4102, Australia
| | - Jake W O'Brien
- Queensland Alliance for Environmental Health Sciences (QAEHS), The University of Queensland, Woolloongabba, QLD, 4102, Australia
| | - Peter J Cabot
- School of Pharmacy, The University of Queensland, Woolloongabba, QLD, 4102, Australia
| | - Wayne D Hall
- Queensland Alliance for Environmental Health Sciences (QAEHS), The University of Queensland, Woolloongabba, QLD, 4102, Australia; Centre for Youth Substance Abuse Research, The University of Queensland, Herston, QLD, 4029, Australia
| | - Jochen F Mueller
- Queensland Alliance for Environmental Health Sciences (QAEHS), The University of Queensland, Woolloongabba, QLD, 4102, Australia
| | - Kevin V Thomas
- Queensland Alliance for Environmental Health Sciences (QAEHS), The University of Queensland, Woolloongabba, QLD, 4102, Australia
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26
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Uhelski ML, Bruce D, Speltz R, Wilcox GL, Simone DA. Topical Application of Loperamide/Oxymorphindole, Mu and Delta Opioid Receptor Agonists, Reduces Sensitization of C-fiber Nociceptors that Possess Na V1.8. Neuroscience 2020; 446:102-112. [PMID: 32858141 DOI: 10.1016/j.neuroscience.2020.08.022] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/10/2019] [Revised: 06/27/2020] [Accepted: 08/17/2020] [Indexed: 01/09/2023]
Abstract
It was recently shown that local injection, systemic administration or topical application of the peripherally-restricted mu-opioid receptor (MOR) agonist loperamide (Lo) and the delta-opioid receptor (DOR) agonist oxymorphindole (OMI) synergized to produce highly potent anti-hyperalgesia that was dependent on both MOR and DOR located in the periphery. We assessed peripheral mechanisms by which this Lo/OMI combination produces analgesia in mice expressing the light-sensitive protein channelrhodopsin2 (ChR2) in neurons that express NaV1.8 voltage-gated sodium channels. These mice (NaV1.8-ChR2+) enabled us to selectively target and record electrophysiological activity from these neurons (the majority of which are nociceptive) using blue light stimulation of the hind paw. We assessed the effect of Lo/OMI on nociceptor activity in both naïve mice and mice treated with complete Freund's adjuvant (CFA) to induce chronic inflammation of the hind paw. Teased fiber recording of tibial nerve fibers innervating the plantar hind paw revealed that the Lo/OMI combination reduced responses to light stimulation in naïve mice and attenuated spontaneous activity (SA) as well as responses to light and mechanical stimuli in CFA-treated mice. These results show that Lo/OMI reduces activity of C-fiber nociceptors that express NaV1.8 and corroborate recent behavioral studies demonstrating the potent analgesic effects of this drug combination. Because of its peripheral site of action, Lo/OMI might produce effective analgesia without the side effects associated with activation of opioid receptors in the central nervous system.
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Affiliation(s)
- Megan L Uhelski
- Department of Diagnostic & Biological Sciences, School of Dentistry, University of Minnesota, Minneapolis, MN 55455, USA
| | - Daniel Bruce
- Department of Neuroscience, University of Minnesota, Minneapolis, MN 55455, USA
| | - Rebecca Speltz
- Department of Diagnostic & Biological Sciences, School of Dentistry, University of Minnesota, Minneapolis, MN 55455, USA; Department of Neuroscience, University of Minnesota, Minneapolis, MN 55455, USA
| | - George L Wilcox
- Department of Neuroscience, University of Minnesota, Minneapolis, MN 55455, USA; Department of Pharmacology, University of Minnesota, Minneapolis, MN 55455, USA; Department of Dermatology, University of Minnesota, Minneapolis, MN 55455, USA
| | - Donald A Simone
- Department of Diagnostic & Biological Sciences, School of Dentistry, University of Minnesota, Minneapolis, MN 55455, USA.
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27
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Yung EM, Got TC, Patel N, Brull R, Abdallah FW. Intra-articular infiltration analgesia for arthroscopic shoulder surgery: a systematic review and meta-analysis. Anaesthesia 2020; 76:549-558. [PMID: 32596840 DOI: 10.1111/anae.15172] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 06/03/2020] [Indexed: 12/18/2022]
Abstract
Phrenic-sparing analgesic techniques for shoulder surgery are desirable. Intra-articular infiltration analgesia is one promising phrenic-sparing modality, but its role remains unclear because of conflicting evidence of analgesic efficacy and theoretical concerns regarding chondrotoxicity. This systematic review and meta-analysis evaluated the benefits and risks of intra-articular infiltration in arthroscopic shoulder surgery compared with systemic analgesia or interscalene brachial plexus block. We sought randomised controlled trials comparing intra-articular infiltration with interscalene brachial plexus block or systemic analgesia (control). Cumulative 24-h postoperative oral morphine equivalent consumption was designated as the primary outcome. Secondary outcomes included visual analogue scale pain scores during the first 24 h postoperatively; time-to-first analgesic request; patient satisfaction; opioid-related side-effects; block-related adverse events; and any indicators of chondrotoxicity. Fifteen trials (863 patients) were included. Compared with control, intra-articular infiltration reduced 24-h postoperative analgesic consumption by a weighted mean difference (95%CI) of -30.9 ([-38.9 to -22.9]; p < 0.001). Intra-articular infiltration also reduced the weighted mean difference (95%CI) pain scores up to 12 h postoperatively, with the greatest reduction at 4 h (-2.2 cm [(-4.4 to -0.04]); p < 0.05). Compared with interscalene brachial plexus block, there was no difference in opioid consumption, but patients receiving interscalene brachial plexus block had better pain scores at 2, 4 and 24 h postoperatively. There was no difference in opioid- or block-related adverse events, and none of the trials reported chondrotoxic effects. Compared with systemic analgesia, intra-articular infiltration provides superior pain control, reduces opioid consumption and enhances patient satisfaction, but it may be inferior to interscalene brachial plexus block patients having arthroscopic shoulder surgery.
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Affiliation(s)
- E M Yung
- Department of Anesthesiology and Pain Medicine, University of Toronto, Canada
| | - T C Got
- Department of Anesthesiology and Pain Medicine, University of Toronto, Canada
| | - N Patel
- Faculty of Medicine, University of British Columbia, Canada
| | - R Brull
- Department of Anesthesiology and Pain Medicine, University of Toronto, Canada
| | - F W Abdallah
- Department of Anesthesiology and Pain Medicine, University of Toronto, Canada.,Department of Anesthesiology and Pain Medicine, University of Ottawa, Canada
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28
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Kościelniak-Merak B, Batko I, Kobylarz K, Sztefko K, Kocot-Kępska M, Tomasik PJ. Impact of Intravenous, Perioperative-Administrated Lidocaine on Postoperative Serum Levels of Endogenous Opioids in Children. Curr Pharm Des 2020; 25:3209-3215. [PMID: 31317834 DOI: 10.2174/1381612825666190718153209] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/20/2019] [Accepted: 07/12/2019] [Indexed: 11/22/2022]
Abstract
BACKGROUND Endogenous opioids are neuropeptides involved in pain-relieving processes. In the periphery, they are synthesised and stored in cells of the immune system. OBJECTIVE In the current study, we describe the influence of perioperative, intravenous (i.v.) lidocaine infusion in children on postoperative, serum endogenous opioid concentrations in children. METHODS Forty-four children undergoing major spinal surgery were enrolled in the cohort study. They were divided into two groups: group A (n = 21) generally anesthetised with fentanyl, propofol, rocuronium, a mixture of oxygen/air/sevoflurane and with analgetics and co-analgetics: morphine, acetaminophen, metamizole, gabapentin, dexamethason and group B (n = 23) where, in addition to the above-described general anesthesia, patients were given i.v. lidocaine as a co-analgesic. We also recruited 20 healthy age- and gender-matched children (group C). We measured endogenous opioid levels in serum using immunoenzymatic methods. We evaluated postoperative pain intensity using a numerical or visual pain scale and demand for morphine. RESULTS The levels of measured endogenous opioids were similar in the control and in the studied groups before surgery. We noted that group B patients had lower pain intensity when compared to group A subjects. In group B, the elevated serum concentrations of β-endorphin, enkephalin and dynorphin in the postoperative period were reported. We also observed that the levels of endogenous opioids negatively correlated with morphine requirements and positively correlated with lidocaine concentration. CONCLUSION Multidrug pain management including lidocaine seems to be more efficient than models without lidocaine. The endogenous opioid system should be considered as a novel target for pain relief therapy in children.
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Affiliation(s)
- Barbara Kościelniak-Merak
- Department of Clinical Biochemistry, Pediatrics Institute, Jagiellonian University Medical College, Wielicka St 265, 30-663 Cracow, Poland
| | - Ilona Batko
- Intensive Care Unit, University Children's Hospital, Wielicka St 265, 30-663 Cracow, Poland
| | - Krzysztof Kobylarz
- Intensive Care Unit, University Children's Hospital, Wielicka St 265, 30-663 Cracow, Poland.,Department of Anesthesiology and Intensive Care, Jagiellonian University Medical College, Kopernika St. 17, 31-501 Cracow, Poland
| | - Krystyna Sztefko
- Department of Clinical Biochemistry, Pediatrics Institute, Jagiellonian University Medical College, Wielicka St 265, 30-663 Cracow, Poland
| | - Magdalena Kocot-Kępska
- Department of Pain Research and Treatment, Jagiellonian University Medical College, Śniadeckich St 10, 31-501 Cracow, Poland
| | - Przemysław J Tomasik
- Department of Clinical Biochemistry, Pediatrics Institute, Jagiellonian University Medical College, Wielicka St 265, 30-663 Cracow, Poland
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29
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Kim GH, Lee JW, Kim GE, Lee SS, Son SL, Kim BU, Cho HN, Kwon MY, Koo MS, Kim JE, Yun MJ. Analgesic effect of ropivacaine with fentanyl in comparison with ropivacaine alone for continuous femoral nerve block after knee replacement arthroplasty: a prospective, randomized, double-blinded study. Anesth Pain Med (Seoul) 2020; 15:209-216. [PMID: 33329816 PMCID: PMC7713827 DOI: 10.17085/apm.2020.15.2.209] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/25/2019] [Revised: 06/19/2019] [Accepted: 07/15/2019] [Indexed: 12/17/2022] Open
Abstract
Background The analgesic effect of perineural opioid in clinical practice are still controversial. This randomized controlled trial compared analgesic effect of ropivacaine with fentanyl or ropivacaine alone for continuous femoral nerve block following unilateral total knee arthroplasty. Methods Fourty patients of ASA PS Ⅰ or Ⅱ receiving total knee arthroplasty with spinal anesthesia were enlisted and randomly allocated into two groups. Group R; bolus injection of 0.375% ropivacaine, 30 ml and an infusion of 0.2% ropivacaine at 8 ml/h (n = 20). Group RF; 0.375% ropivacaine, 29 ml added with 50 μg of fentanyl as a bolus and an infusion of 0.2% ropivacaine mixed with 1 μg/ml of fentanyl at 8 ml/h (n = 20). Local anesthetic infusion via a femoral nerve catheter was started at the end of operation and continued for 48 h. Intravenous patient-controlled analgesia with hydromorphone (0.15 mg/ml, 0-1-10) were used for adjuvant analgesics. Position of catheter tip and contrast distribution, visual analogue scale of pain, hydromorphone consumption, side effects were recorded for 48 h after operation. Patient satisfaction for the pain control received were noted. Results The pain visual analogue scale, incidences of side effects and satisfaction were not different between the two groups (P > 0.05), but the hydromorphone usage at 48 h after operation were lower in the Group RF than in the Group R (P = 0.047). Conclusions The analgesic effect of ropivacaine with fentanyl for continuous femoral nerve block after knee replacement arthroplasty was not superior to that of the ropivacaine alone.
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Affiliation(s)
- Gunn Hee Kim
- Department of Anesthesiology and Pain Medicine, National Medical Center, Seoul, Korea
| | - Joon Woo Lee
- Department of Radiology, Seoul National University Bundang Hospital, Seongnam, Korea
| | - Go Eun Kim
- Department of Anesthesiology and Pain Medicine, National Medical Center, Seoul, Korea
| | - Seong Su Lee
- Department of Anesthesiology and Pain Medicine, National Medical Center, Seoul, Korea
| | - Shill Lee Son
- Department of Anesthesiology and Pain Medicine, National Medical Center, Seoul, Korea
| | - Byung Uk Kim
- Department of Anesthesiology and Pain Medicine, National Medical Center, Seoul, Korea
| | - Ha Na Cho
- Department of Anesthesiology and Pain Medicine, National Medical Center, Seoul, Korea
| | - Mi Young Kwon
- Department of Anesthesiology and Pain Medicine, National Medical Center, Seoul, Korea
| | - Min Seok Koo
- Department of Anesthesiology and Pain Medicine, National Medical Center, Seoul, Korea
| | - Ji Eun Kim
- Department of Anesthesiology and Pain Medicine, National Medical Center, Seoul, Korea
| | - Mi Jung Yun
- Department of Anesthesiology and Pain Medicine, National Medical Center, Seoul, Korea
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30
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Summers S, Mohile N, McNamara C, Osman B, Gebhard R, Hernandez VH. Analgesia in Total Knee Arthroplasty: Current Pain Control Modalities and Outcomes. J Bone Joint Surg Am 2020; 102:719-727. [PMID: 31985507 DOI: 10.2106/jbjs.19.01035] [Citation(s) in RCA: 29] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/01/2023]
Affiliation(s)
- Spencer Summers
- Departments of Orthopaedics and Rehabilitation (S.S., N.M., C.M., and V.H.H.), and Anesthesiology, Perioperative Medicine, and Pain Management (B.O. and R.G.), University of Miami, Miami, Florida
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31
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El Sherif FA, Abd El-Rahman AM, Othman AH, Shouman SA, Omran MM, Hassan NA, Hassan SB, Aboeleuon E. Analgesic Effect of Morphine Added to Bupivacaine in Serratus Anterior Plane Block Following Modified Radical Mastectomy. Only a Local Effect? Randomized Clinical Trial. J Pain Res 2020; 13:661-668. [PMID: 32280268 PMCID: PMC7127777 DOI: 10.2147/jpr.s236336] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/29/2019] [Accepted: 03/07/2020] [Indexed: 11/23/2022] Open
Abstract
Background Serratus anterior plane (SAP) block, a novel regional anesthetic procedure, involves the anterolateral chest wall. Opioid receptors have been found on peripheral nerve terminals, so morphine may have a local action. Objective This work aimed at exploring the analgesic efficacy of morphine added to bupivacaine in SAPB in patients for whom modified radical mastectomy was conducted and whether it is a mere local effect. Methods Forty female patients were planned to have modified radical mastectomy participated in the study. Patients were randomly divided into two groups; Control group (C): received ultrasound-guided serratus anterior plane block with 20 mL of bupivacaine hydrochloride 0.25%; Morphine group (M): received the same in addition to 10 mg morphine sulfate. Intra- and post-operative blood samples were taken for the assessment of morphine serum levels. All patients were assessed for VAS scores during rest and movement (VAS-R and VAS-M). Time to the first request and the total amount of the rescue analgesia were recorded. Results In group M, Morphine was not detected in the plasma of all patients. Both VAS-R and VAS-M were significantly higher in group C than in group M (P<0.001) and (P≤0.003), respectively. Time to the first request of rescue analgesia was 8.5 h in group C compared to 20 h in group M (P=0.005) with a median dose of acetaminophen consumption of 2 g in group C compared to 1 g in group M (P=0.006). Conclusion Ten mg of morphine, when added to bupivacaine in SAPB, improved postoperative analgesia in patients to whom modified radical mastectomy was conducted. This effect seems to be attributed merely to local mechanisms. Registration The registration number of this study is NCT02962024 at www.clinicaltrial.gov.
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Affiliation(s)
- Fatma A El Sherif
- Anesthesia, ICU, and Pain Relief, South Egypt Cancer Institute, Assiut University, Assiut, Egypt
| | - Ahmad M Abd El-Rahman
- Anesthesia, ICU, and Pain Relief, South Egypt Cancer Institute, Assiut University, Assiut, Egypt
| | - Ahmed H Othman
- Anesthesia, ICU, and Pain Relief, South Egypt Cancer Institute, Assiut University, Assiut, Egypt
| | - Samia A Shouman
- Cancer Biology, National Cancer Institute, Cairo University, Cairo, Egypt
| | - Mervat M Omran
- Cancer Biology (Pharmacology and Experimental Oncology), National Cancer Institute, Cairo University, Cairo, Egypt
| | - Nivin A Hassan
- Cancer Biology (Pharmacology and Experimental Oncology), South Egypt Cancer Institute, Assuit University, Assiut, Egypt
| | - Sahar B Hassan
- Clinical Pharmacy, Faculty of Pharmacy, Assuit University, Assiut, Egypt
| | - Ebrahim Aboeleuon
- Surgical Oncology, South Egypt Cancer Institute, Assiut University, Assiut, Egypt
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32
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Saunders DP, Rouleau T, Cheng K, Yarom N, Kandwal A, Joy J, Bektas Kayhan K, van de Wetering M, Brito-Dellan N, Kataoka T, Chiang K, Ranna V, Vaddi A, Epstein J, Lalla RV, Bossi P, Elad S. Systematic review of antimicrobials, mucosal coating agents, anesthetics, and analgesics for the management of oral mucositis in cancer patients and clinical practice guidelines. Support Care Cancer 2020; 28:2473-2484. [PMID: 32052137 DOI: 10.1007/s00520-019-05181-6] [Citation(s) in RCA: 40] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/02/2019] [Accepted: 11/07/2019] [Indexed: 12/27/2022]
Abstract
PURPOSE To update the clinical practice guidelines for the use of antimicrobials, mucosal coating agents, anesthetics, and analgesics for the prevention and/or treatment of oral mucositis (OM). METHODS A systematic review was conducted by the Mucositis Study Group of the Multinational Association of Supportive Care in Cancer/International Society of Oral Oncology (MASCC/ISOO). The body of evidence for each intervention, in each cancer treatment setting, was assigned an evidence level. The findings were added to the database used to develop the 2014 MASCC/ISOO clinical practice guidelines. Based on the evidence level, the following guidelines were determined: Recommendation, Suggestion, and No Guideline Possible. RESULTS A total of 9 new papers were identified within the scope of this section, adding to the 62 papers reviewed in this section previously. A new Suggestion was made for topical 0.2% morphine for the treatment of OM-associated pain in head and neck (H&N) cancer patients treated with RT-CT (modification of previous guideline). A previous Recommendation against the use of sucralfate-combined systemic and topical formulation in the prevention of OM in solid cancer treatment with CT was changed from Recommendation Against to No Guideline Possible. Suggestion for doxepin and fentanyl for the treatment of mucositis-associated pain in H&N cancer patients was changed to No Guideline Possible. CONCLUSIONS Of the agents studied for the management of OM in this paper, the evidence supports a Suggestion in favor of topical morphine 0.2% in H&N cancer patients treated with RT-CT for the treatment of OM-associated pain.
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Affiliation(s)
- Deborah P Saunders
- Dental Oncology Program, Health Sciences North, North East Cancer Center, Northern Ontario School of Medicine, 41 Ramsey Lake Road, Sudbury, Ontario, P3E 5J1, Canada.
| | - Tanya Rouleau
- Dental Oncology Program, Health Sciences North, North East Cancer Center, Northern Ontario School of Medicine, 41 Ramsey Lake Road, Sudbury, Ontario, P3E 5J1, Canada
| | - Karis Cheng
- Alice Lee Centre for Nursing Studies, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
| | - Noam Yarom
- Oral Medicine Unit, Sheba Medical Center, Tel Hashomer, Israel and School of Dental Medicine, Tel Aviv University, Tel Aviv, Israel
| | - Abhishek Kandwal
- Cancer Research Institute, Himalayan Institute of Medical Sciences, Swami Rama Himayalan University, Dehradun, Uttarakhand, India
| | - Jamie Joy
- Clinical Pharmacy, Cancer Treatment Centers of America, Boca Raton, FL, USA
| | - Kivanc Bektas Kayhan
- Department of Oral and Maxillofacial Surgery, Faculty of Dentistry, İstanbul University, Istanbul, Turkey
| | - Marianne van de Wetering
- Paediatric Oncology Department, Emma Children's Hospital, Academic Medical Centre, Amsterdam, The Netherlands
| | - Norman Brito-Dellan
- Division of General Internal Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Tomoko Kataoka
- Multi-institutional Clinical Trials Section, Research Management Division, Clinical Research Support Office, National Cancer Center Hospital, Tokyo, Japan
| | - Karen Chiang
- Pharmacy Department, St Vincent's Hospital Melbourne, Electronic Medical Records Department, Melbourne Health, Jane Bell House, Melbourne, Victoria, Australia
| | - Vinisha Ranna
- Department of Oral and Maxillofacial Surgery, The Mount Sinai Hospital, New York, NY, USA
| | - Anusha Vaddi
- Oral Medicine, Eastman Institute for Oral Health, University of Rochester Medical Center, Rochester, NY, USA
| | - Joel Epstein
- Cedars-Sinai Health System, Los Angeles CA and City of Hope National Medical Center, Duarte, CA, USA
| | - Rajesh V Lalla
- Section of Oral Medicine, University of Connecticut School of Dental Medicine, Farmington, CT, USA
| | - Paolo Bossi
- Medical Oncology, University of Brescia, ASST-Spedali Civili, Brescia, Italy
| | - Sharon Elad
- Oral Medicine, Eastman Institute for Oral Health, University of Rochester Medical Center, Rochester, NY, USA
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Hong JS, Moran MT, Eaton LA, Grafton LM. Neurologic, Cognitive, and Behavioral Consequences of Opioid Overdose: a Review. CURRENT PHYSICAL MEDICINE AND REHABILITATION REPORTS 2019. [DOI: 10.1007/s40141-019-00247-2] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
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Alghofaily M, Romberg E, Aldahmash S, Tordik PA. Opioid-prescribing Habits of Practitioner and Educator Members of the American Association of Endodontists: Report of a National Survey. J Endod 2019; 45:1265-1271. [DOI: 10.1016/j.joen.2019.06.007] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/19/2018] [Revised: 05/12/2019] [Accepted: 06/19/2019] [Indexed: 10/26/2022]
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Abstract
Balanced general anesthesia, the most common management strategy used in anesthesia care, entails the administration of different drugs together to create the anesthetic state. Anesthesiologists developed this approach to avoid sole reliance on ether for general anesthesia maintenance. Balanced general anesthesia uses less of each drug than if the drug were administered alone, thereby increasing the likelihood of its desired effects and reducing the likelihood of its side effects. To manage nociception intraoperatively and pain postoperatively, the current practice of balanced general anesthesia relies almost exclusively on opioids. While opioids are the most effective antinociceptive agents, they have undesirable side effects. Moreover, overreliance on opioids has contributed to the opioid epidemic in the United States. Spurred by concern of opioid overuse, balanced general anesthesia strategies are now using more agents to create the anesthetic state. Under these approaches, called “multimodal general anesthesia,” the additional drugs may include agents with specific central nervous system targets such as dexmedetomidine and ones with less specific targets, such as magnesium. It is postulated that use of more agents at smaller doses further maximizes desired effects while minimizing side effects. Although this approach appears to maximize the benefit-to-side effect ratio, no rational strategy has been provided for choosing the drug combinations. Nociception induced by surgery is the primary reason for placing a patient in a state of general anesthesia. Hence, any rational strategy should focus on nociception control intraoperatively and pain control postoperatively. In this Special Article, we review the anatomy and physiology of the nociceptive and arousal circuits, and the mechanisms through which commonly used anesthetics and anesthetic adjuncts act in these systems. We propose a rational strategy for multimodal general anesthesia predicated on choosing a combination of agents that act at different targets in the nociceptive system to control nociception intraoperatively and pain postoperatively. Because these agents also decrease arousal, the doses of hypnotics and/or inhaled ethers needed to control unconsciousness are reduced. Effective use of this strategy requires simultaneous monitoring of antinociception and level of unconsciousness. We illustrate the application of this strategy by summarizing anesthetic management for 4 representative surgeries.
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Hughes L, Patterson SD. Low intensity blood flow restriction exercise: Rationale for a hypoalgesia effect. Med Hypotheses 2019; 132:109370. [PMID: 31442920 DOI: 10.1016/j.mehy.2019.109370] [Citation(s) in RCA: 30] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/05/2019] [Revised: 08/07/2019] [Accepted: 08/16/2019] [Indexed: 12/13/2022]
Abstract
Exercise-induced hypoalgesia is characterised by a reduction in pain sensitivity following exercise. Recently, low intensity exercise performed with blood flow restriction has been shown to induce hypoalgesia. The purpose of this manuscript is to discuss the mechanisms of exercise-induced hypoalgesia and provide rationale as to why low intensity exercise performed with blood flow restriction may induce hypoalgesia. Research into exercise-induced hypoalgesia has identified several potential mechanisms, including opioid and endocannabinoid-mediated pain inhibition, conditioned pain modulation, recruitment of high threshold motor units, exercise-induced metabolite production and an interaction between cardiovascular and pain regulatory systems. We hypothesise that several mechanisms consistent with prolonged high intensity exercise may drive the hypoalgesia effect observed with blood flow restriction exercise. These are likely triggered by the high level of intramuscular stress in the exercising muscle generated by blood flow restriction including hypoxia, accumulation of metabolites, accelerated fatigue onset and ischemic pain. Therefore, blood flow restriction exercise may induce hypoalgesia through similar mechanisms to prolonged higher intensity exercise, but at lower intensities, by changing local tissue physiology, highlighting the importance of the blood flow restriction stimulus. The potential to use blood flow restriction exercise as a pain modulation tool has important implications following acute injury and surgery, and for several load compromised populations with chronic pain.
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Affiliation(s)
- Luke Hughes
- Faculty of Sport, Health and Applied Science, St Mary's University, London TW1 4SX, UK.
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A Novel Application of Buprenorphine Transdermal Patch to Relieve Pain in the Knee Joint of Knee Osteoarthritis Patients: A Retrospective Case-Control Study. J Clin Med 2019; 8:jcm8071009. [PMID: 31295896 PMCID: PMC6678725 DOI: 10.3390/jcm8071009] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/05/2019] [Revised: 07/04/2019] [Accepted: 07/05/2019] [Indexed: 01/08/2023] Open
Abstract
Osteoarthritis (OA) is considered to be one of the most disabling diseases. The intra-articular opioid injection has been widely studied for its simplicity, safety, and efficacy in OA. In this study, however, we suggest a novel method of buprenorphine transdermal patch (BTDP) to painful knee joints of OA patients, instead of intra-articular opioid injection, and subsequently compared the knee application with conventional chest application. We retrospectively enrolled 213 patients with knee OA who did not respond to conventional therapy. The Numeric Rating Scale (NRS), adverse effects, and compliance were recorded before and after the application of the BTDP. All parameters were compared between the knee applied group and the chest applied group. After the BTDP application, the NRS score in the knee applied group was lower than that of the chest applied group (p = 0.007). NRS scores after buprenorphine patch decreased to 2.21 ± 0.77, and 2.55 ± 0.71 in the chest applied group and the knee applied group, respectively. The adverse effects were 19.32% in the knee applied group, and 64.00% in the chest applied group. The compliances were 82.95% and 37.60% in the knee applied group and chest applied group, respectively. This novel application of BTDP directly to the painful knee joint of knee OA patients led to a decrease in the NRS score, adverse effects, and an increase in compliance compared with the chest application method.
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Abstract
Bone cancer metastasis is extremely painful and decreases the quality of life of the affected patients. Available pharmacological treatments are not able to sufficiently ameliorate the pain, and as patients with cancer are living longer, new treatments for pain management are needed. Decitabine (5-aza-2'-deoxycytidine), a DNA methyltransferases inhibitor, has analgesic properties in preclinical models of postsurgical and soft-tissue oral cancer pain by inducing an upregulation of endogenous opioids. In this study, we report that daily treatment with decitabine (2 µg/g, intraperitoneally) attenuated nociceptive behavior in the 4T1-luc2 mouse model of bone cancer pain. We hypothesized that the analgesic mechanism of decitabine involved activation of the endogenous opioid system through demethylation and reexpression of the transcriptionally silenced endothelin B receptor gene, Ednrb. Indeed, Ednrb was hypermethylated and transcriptionally silenced in the mouse model of bone cancer pain. We demonstrated that expression of Ednrb in the cancer cells lead to release of β-endorphin in the cell supernatant, which reduced the number of responsive dorsal root ganglia neurons in an opioid-dependent manner. Our study supports a role of demethylating drugs, such as decitabine, as unique pharmacological agents targeting the pain in the cancer microenvironment.
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Corkrum M, Rothwell PE, Thomas MJ, Kofuji P, Araque A. Opioid-Mediated Astrocyte-Neuron Signaling in the Nucleus Accumbens. Cells 2019; 8:cells8060586. [PMID: 31207909 PMCID: PMC6628279 DOI: 10.3390/cells8060586] [Citation(s) in RCA: 51] [Impact Index Per Article: 8.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/13/2019] [Revised: 06/08/2019] [Accepted: 06/11/2019] [Indexed: 12/29/2022] Open
Abstract
Major hallmarks of astrocyte physiology are the elevation of intracellular calcium in response to neurotransmitters and the release of neuroactive substances (gliotransmitters) that modulate neuronal activity. While μ-opioid receptor expression has been identified in astrocytes of the nucleus accumbens, the functional consequences on astrocyte–neuron communication remains largely unknown. The present study has investigated the astrocyte responsiveness to μ-opioid signaling and the regulation of gliotransmission in the nucleus accumbens. Through the combination of calcium imaging and whole-cell patch clamp electrophysiology in brain slices, we have found that μ-opioid receptor activation in astrocytes elevates astrocyte cytoplasmic calcium and stimulates the release of the gliotransmitter glutamate, which evokes slow inward currents through the activation of neuronal N-methyl-D-aspartate (NMDA) receptors. These results indicate the existence of molecular mechanisms underlying opioid-mediated astrocyte–neuron signaling in the nucleus accumbens.
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Affiliation(s)
- Michelle Corkrum
- Department of Neuroscience, University of Minnesota, Minneapolis, MN 55455, USA.
| | - Patrick E Rothwell
- Department of Neuroscience, University of Minnesota, Minneapolis, MN 55455, USA.
| | - Mark J Thomas
- Department of Neuroscience, University of Minnesota, Minneapolis, MN 55455, USA.
| | - Paulo Kofuji
- Department of Neuroscience, University of Minnesota, Minneapolis, MN 55455, USA.
| | - Alfonso Araque
- Department of Neuroscience, University of Minnesota, Minneapolis, MN 55455, USA.
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Evaluation of soluble fentanyl microneedles for loco-regional anti-nociceptive activity. Int J Pharm 2019; 564:485-491. [DOI: 10.1016/j.ijpharm.2019.04.066] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/21/2018] [Revised: 04/02/2019] [Accepted: 04/22/2019] [Indexed: 12/20/2022]
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Iwakiri K, Ohta Y, Minoda Y, Kobayashi A, Nakamura H. Effect of periarticular morphine injection for total hip arthroplasty: a randomised, double-blind trial. Hip Int 2019; 29:245-252. [PMID: 29890864 DOI: 10.1177/1120700018780067] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
BACKGROUND The periarticular multimodal cocktail injection is currently commonly used to treat postoperative pain after total hip arthroplasty (THA). Despite its analgesic effect, it is frequently reported to cause nausea and vomiting, which are adverse effects of opioids. This study aimed to assess the efficacy of morphine as a component of a multimodal cocktail injection for providing postoperative analgesia and alleviating swelling in patients who underwent THA. MATERIALS AND METHODS This was a prospective, single-centre, randomised controlled trial involving 100 patients scheduled for unilateral THA. A mixture of steroids, local anaesthetics, NSAIDs, and epinephrine with or without morphine (0.1 mg/kg), was injected into randomly assigned patients. Postoperative assessment was performed with all attending personnel and patients blind to group assignment. Visual analogue scale (VAS) of pain, range of motion (ROM), nausea numerical rating scale (NRS), the total dose of antiemetic drugs used and thigh swelling were compared between groups on postoperative days. RESULTS Pain VAS scores both at rest and on motion did not differ between the 2 groups at any postoperative time-point. The nausea NRS scores during the postoperative period from 0 minutes to 1 hour and the total dose of antiemetic drugs administered were significantly higher in the morphine group. The thigh girth showed no difference between groups on any of the postoperative days. CONCLUSIONS The results of this study suggested that addition of morphine to the multimodal cocktail injection after THA is not effective for relieving postoperative pain, alleviating swelling, or improving ROM, and results in nausea and vomiting. Randomised controlled trial registration number UMIN000022668.
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Affiliation(s)
- Kentaro Iwakiri
- 1 Department of Orthopaedic Surgery, Shiraniwa Hospital Joint Arthroplasty Centre, Nara, Japan
| | - Yoichi Ohta
- 2 Department of Orthopaedic Surgery, Osaka City University Graduate School of Medicine, Osaka, Japan
| | - Yukihide Minoda
- 2 Department of Orthopaedic Surgery, Osaka City University Graduate School of Medicine, Osaka, Japan
| | - Akio Kobayashi
- 1 Department of Orthopaedic Surgery, Shiraniwa Hospital Joint Arthroplasty Centre, Nara, Japan
| | - Hiroaki Nakamura
- 2 Department of Orthopaedic Surgery, Osaka City University Graduate School of Medicine, Osaka, Japan
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Kido K, Shindo Y, Toda S, Masaki E. Expression of β-endorphin in peripheral tissues after systemic administration of lipopolysaccharide as a model of endotoxic shock in mice. ANNALES D'ENDOCRINOLOGIE 2019; 80:117-121. [DOI: 10.1016/j.ando.2018.06.001] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/31/2017] [Revised: 05/22/2018] [Accepted: 06/05/2018] [Indexed: 02/08/2023]
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Tatch W. Opioid Prescribing Can Be Reduced in Oral and Maxillofacial Surgery Practice. J Oral Maxillofac Surg 2019; 77:1771-1775. [PMID: 30980813 DOI: 10.1016/j.joms.2019.03.009] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/05/2018] [Revised: 03/06/2019] [Accepted: 03/08/2019] [Indexed: 10/27/2022]
Abstract
PURPOSE Pain management is one of the most critical aspects of practice in oral and maxillofacial surgery. The purpose of this study was to measure the change in strong (stronger than codeine 30 mg) opioid use after introducing the standardized protocol ("office protocol") designed for opioid-free postoperative pain management. MATERIALS AND METHODS This is a retrospective cohort study of patients who had surgical procedures performed at the NorthShore Center for Oral and Facial Surgery (Gurnee, IL). Data of patients who underwent qualified surgical procedures and filled prescriptions for strong opioids before and after introduction of the office protocol were analyzed. The primary predictor variable was introduction of the office protocol. The primary outcome variable was filling of a strong opioid prescription that was correlated to pain control as assessed by patients. Age and gender distributions also were analyzed. Proportions and associated 95% confidence intervals were used to compare the number of hydrocodone or oxycodone (strong) prescriptions filled by patients during a 3-year interval. RESULTS In March 2016, the office protocol for pain management, designed to decrease opioid use, was introduced. In 2015 (before introduction of the office protocol), 2,016 adult patients (15 to 85 yr old) underwent qualified surgical procedures at the author's practice, 1,184 (59%) of whom required and filled strong opioid prescriptions. In 2017 (2 yr after introduction of the office procedure) that number decreased to 19%, whereas the number of qualified surgical procedures performed remained relatively the same between the years. Postoperative pain control was not qualitatively measured but was assumed adequate and correlated with the filling of a strong opioid prescription or requiring a refill, which would be recorded as part of total prescriptions filled. CONCLUSION A 3-fold decrease in hydrocodone or oxycodone prescription fill was seen at the 2-year interval. As alternatives, nonsteroidal anti-inflammatory drugs, acetaminophen, and a homeopathic recovery kit (Vega Recovery Kit, StellaLife, Glenview, IL) were used for pain management for patients undergoing various oral surgery procedures.
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Abstract
Persistent, in particular neuropathic pain affects millions of people worldwide. However, the response rate of patients to existing analgesic drugs is less than 50%. There are several possibilities to increase this response rate, such as optimization of the pharmacokinetic and pharmacodynamic properties of analgesics. Another promising approach is to use prognostic biomarkers in patients to determine the optimal pharmacological therapy for each individual. Here, we discuss recent efforts to identify plasma and CSF biomarkers, as well as genetic biomarkers and sensory testing, and how these readouts could be exploited for the prediction of a suitable pharmacological treatment. Collectively, the information on single biomarkers may be stored in knowledge bases and processed by machine-learning and related artificial intelligence techniques, resulting in the optimal pharmacological treatment for individual pain patients. We highlight the potential for biomarker-based individualized pain therapies and discuss biomarker reliability and their utility in clinical practice, as well as limitations of this approach.
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Maktabi M, Kamali A, Jelodar HT, Shokrpour M. Comparison of Topical and Subcutaneous Bupivacaine Infiltration with Subcutaneous Ketamine on Postoperative Pain in Total Abdominal Hysterectomy. Med Arch 2019; 73:15-18. [PMID: 31097853 PMCID: PMC6445620 DOI: 10.5455/medarh.2019.73.15-18] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/05/2019] [Accepted: 02/17/2019] [Indexed: 11/05/2022] Open
Abstract
INTRODUCTION Hysterectomy is one of the most common surgical procedures. Problems such as severe pelvic pain, irregular or heavy bleeding and uterine cancer from those that may be used to treat them no choice but to remove the uterus by surgery. Abdominal pain after abdominal hysterectomy, the most common complaints of patients undergoing this type of surgery is considered. AIM This study aimed to compare the effects of bupivacaine into the subcutaneous tissue and skin ketamine for pain control after surgery in patients undergoing abdominal hysterectomy was performed under general anesthesia. METHODS This study is a randomized, double-blind clinical trial involving 99 women scheduled for TAH referred to tertiary centers was performed. Group A: 5 mL of 0.25% bupivacaine into the subcutaneous tissue and, Group II: 100 mg ketamine skin and subcutaneous tissue with cc5 volume injection, groups of three: cc5 distilled water was injected into the subcutaneous tissue and. The average duration of analgesia and pain and pain score were recorded. RESULTS The average duration of analgesia in group K 65.1±8.8, in the bupivacaine group 65.4±8.7 and in the placebo group 57.6±5.5, which, according to P Value≤0.01 is a significant difference between the three groups were observed, so that the pain in the placebo group for a significant period of ketamine and bupivacaine groups is lower, while that between ketamine and bupivacaine in terms of the average duration of analgesia was no significant difference not. CONCLUSION The results of our study indicate that the use of bupivacaine and ketamine effective in reducing postoperative pain in patients undergoing abdominal hysterectomy tissue and further doses of ketamine and bupivacaine single dose resulted in a significant reduction of postoperative pain patients were compared to the placebo group.
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Affiliation(s)
- Maryam Maktabi
- Department of Gynecology, Arak University of Medical Sciences, Arak, Iran
| | - Alireza Kamali
- Department of Anesthesiology, Arak University of Medical Sciences, Arak, Iran
| | | | - Maryam Shokrpour
- Department of Gynecology, Arak University of Medical Sciences, Arak, Iran
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Ciałkowska-Rysz A, Dzierżanowski T. Topical morphine for treatment of cancer-related painful mucosal and cutaneous lesions: a double-blind, placebo-controlled cross-over clinical trial. Arch Med Sci 2019; 15:146-151. [PMID: 30697265 PMCID: PMC6348368 DOI: 10.5114/aoms.2018.72566] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/30/2017] [Accepted: 07/17/2017] [Indexed: 11/17/2022] Open
Abstract
INTRODUCTION Painful mucosal and cutaneous lesions are often less responsive or even refractory to systemic opioid analgesics. There is evidence suggesting that the effectiveness of topical morphine be restricted to inflammatory pain. The studied groups were small and the observation period relatively short. The aim of this study was to assess the effectiveness and safety of topical morphine for pain related to mucosal lesions and skin ulcers. MATERIAL AND METHODS The study was a 14-day randomized placebo-controlled cross-over trial (RCT) with a 28-day follow-up open phase (OP). The trial was conducted in adult patients with localized cancer-related pain and treated with systemic opioids in an oncology center or home hospice. The patients administered 0.2% gel on the mucosal lesion or 0.2% ointment on the skin lesion by themselves, without restrictions regarding the number of doses per day. The primary measurements were mean pain intensity (MPI) and mean pain relief (MPR) on the numeric rating scale (NRS 0-10), and ITT analysis was performed. RESULTS Thirty-five patients were randomized to the RCT, and all of them completed 14-day observation. The MPI before the treatment was NRS 5.9 and decreased to 2.5 after morphine (p < 0.0001 vs. placebo). The MPR was 57% after morphine, and 77% of the patients using topical morphine obtained clinically significant (at least 50% of the starting value) pain relief, statistically different from placebo. The analgesic effect was sustained over the 28-day OP period (p = 0.00001). There were only 2 cases of moderate pruritus, and no other side effects were reported. CONCLUSIONS Topical morphine was found to be a fast acting, highly effective, and safe medication for mucosal and skin lesions in palliative patients, with a sustainable pain relief effect over the 28-day observation period.
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Sutherland AM, Nicholls J, Bao J, Clarke H. Overlaps in pharmacology for the treatment of chronic pain and mental health disorders. Prog Neuropsychopharmacol Biol Psychiatry 2018; 87:290-297. [PMID: 30055217 DOI: 10.1016/j.pnpbp.2018.07.017] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/14/2017] [Revised: 07/13/2018] [Accepted: 07/18/2018] [Indexed: 12/17/2022]
Abstract
There is significant overlap in the pharmacological management of pain and psychological disorders. Appropriate treatment of patients' comorbid psychological disorders, including sleep disturbances often leads to an improvement in reported pain intensity. The three first line agents for neuropathic pain include tricyclic antidepressants and serotonin norepinephrine reuptake inhibitors which are medications originally developed as antidepressants. The other first line medication for chronic neuropathic pain are anticonvulsant medications initially brought to the market-place for the treatment of epilepsy and are also now being used for the treatment of anxiety disorders and substance withdrawal symptoms. The efficacy of opioids for chronic pain is contentious, but it is agreed that the patients at highest risk for opioid misuse and addiction are patients with underlying psychological disorders who use opioids for their euphoric effects. Similarly, benzodiazepines may present a problem in patients with chronic pain, as up to one third of patients with pain are concomitantly prescribed benzodiazepines, and when combined with other sedating analgesic medications they put patients at increased risk for adverse events and polysubstance misuse. Finally, there is growing evidence for the efficacy of cannabis for treating neuropathic pain, but the consumption of cannabis has been associated with increased risk of psychosis in adolescents, and may be associated with an increased risk for developing bipolar disorder and anxiety disorders. The use of cannabis is associated with an increased risk of substance misuse in both adolescents and adults. In this narrative review, we examine the evidence for the use of several medications used for the treatment of both pain and psychological disorders, and their proposed mechanisms of action, in addition to special concerns for patients with comorbid pain and psychological disorders.
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Affiliation(s)
- Ainsley M Sutherland
- Department of Anesthesia, University of British Columbia, Vancouver, British Columbia, Canada
| | - Judith Nicholls
- Pain Research Unit, Department of Anesthesia and Pain Medicine, Toronto General Hospital, University Health Network, Toronto, Ontario M5G 2C4, Canada
| | - James Bao
- Pain Research Unit, Department of Anesthesia and Pain Medicine, Toronto General Hospital, University Health Network, Toronto, Ontario M5G 2C4, Canada
| | - Hance Clarke
- Pain Research Unit, Department of Anesthesia and Pain Medicine, Toronto General Hospital, University Health Network, Toronto, Ontario M5G 2C4, Canada; Department of Anesthesia, University of Toronto, Toronto, Ontario, Canada.
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Stötzner P, Spahn V, Celik MÖ, Labuz D, Machelska H. Mu-Opioid Receptor Agonist Induces Kir3 Currents in Mouse Peripheral Sensory Neurons - Effects of Nerve Injury. Front Pharmacol 2018; 9:1478. [PMID: 30618766 PMCID: PMC6305728 DOI: 10.3389/fphar.2018.01478] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/20/2018] [Accepted: 12/03/2018] [Indexed: 11/13/2022] Open
Abstract
Neuropathic pain often arises from damage to peripheral nerves and is difficult to treat. Activation of opioid receptors in peripheral sensory neurons is devoid of respiratory depression, sedation, nausea, and addiction mediated in the brain, and ameliorates neuropathic pain in animal models. Mechanisms of peripheral opioid analgesia have therefore gained interest, but the role of G protein-coupled inwardly rectifying potassium (Kir3) channels, important regulators of neuronal excitability, remains unclear. Whereas functional Kir3 channels have been detected in dorsal root ganglion (DRG) neurons in rats, some studies question their contribution to opioid analgesia in inflammatory pain models in mice. However, neuropathic pain can be diminished by activation of peripheral opioid receptors in mouse models. Therefore, here we investigated effects of the selective μ-opioid receptor (MOR) agonist [D-Ala2, N-Me-Phe4, Gly5-ol]-enkephalin (DAMGO) on potassium conductance in DRG neurons upon a chronic constriction injury (CCI) of the sciatic nerve in mice. For verification, we also tested human embryonic kidney (HEK) 293 cells transfected with MOR and Kir3.2. Using patch clamp, we recorded currents at -80 mV and applied voltage ramps in high extracellular potassium concentrations, which are a highly sensitive measures of Kir3 channel activity. We found a significantly higher rate of HEK cells responding with potassium channel blocker barium-sensitive inward current (233 ± 51 pA) to DAMGO application in transfected than in untransfected group, which confirms successful recordings of inward currents through Kir3.2 channels. Interestingly, DAMGO induced similar inward currents (178 ± 36-207 ± 56 pA) in 15-20% of recorded DRG neurons from naïve mice and in 4-27% of DRG neurons from mice exposed to CCI, measured in voltage clamp or voltage ramp modes. DAMGO-induced currents in naïve and CCI groups were reversed by barium and a more selective Kir3 channel blocker tertiapin-Q. These data indicate the coupling of Kir3 channels with MOR in mouse peripheral sensory neuron cell bodies, which was unchanged after CCI. A comparative analysis of opioid-induced potassium conductance at the axonal injury site and peripheral terminals of DRG neurons could clarify the role of Kir3 channel-MOR interactions in peripheral nerve injury and opioid analgesia.
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Affiliation(s)
- Philip Stötzner
- Department of Experimental Anesthesiology, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany
| | - Viola Spahn
- Department of Experimental Anesthesiology, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany
| | - Melih Ö Celik
- Department of Experimental Anesthesiology, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany
| | - Dominika Labuz
- Department of Experimental Anesthesiology, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany
| | - Halina Machelska
- Department of Experimental Anesthesiology, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany
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49
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Scheff NN, Bhattacharya A, Dowse E, Dang RX, Dolan JC, Wang S, Kim H, Albertson DG, Schmidt BL. Neutrophil-Mediated Endogenous Analgesia Contributes to Sex Differences in Oral Cancer Pain. Front Integr Neurosci 2018; 12:52. [PMID: 30405367 PMCID: PMC6204375 DOI: 10.3389/fnint.2018.00052] [Citation(s) in RCA: 37] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/21/2018] [Accepted: 10/01/2018] [Indexed: 01/14/2023] Open
Abstract
The incidence of oral cancer in the United States is increasing, especially in young people and women. Patients with oral cancer report severe functional pain. Using a patient cohort accrued through the New York University Oral Cancer Center and immune-competent mouse models, we identify a sex difference in the prevalence and severity of oral cancer pain. A neutrophil-mediated endogenous analgesic mechanism is present in male mice with oral cancer. Local naloxone treatment potentiates cancer mediator-induced orofacial nociceptive behavior in male mice only. Tongues from male mice with oral cancer have significantly more infiltrating neutrophils compared to female mice with oral cancer. Neutrophils isolated from the cancer-induced inflammatory microenvironment express beta-endorphin and met-enkephalin. Furthermore, neutrophil depletion results in nociceptive behavior in male mice. These data suggest a role for sex-specific, immune cell-mediated endogenous analgesia in the treatment of oral cancer pain.
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Affiliation(s)
- Nicole N Scheff
- Bluestone Center for Clinical Research, New York University, New York, NY, United States
| | - Aditi Bhattacharya
- Bluestone Center for Clinical Research, New York University, New York, NY, United States
| | - Edward Dowse
- College of Dentistry, New York University, New York, NY, United States
| | - Richard X Dang
- College of Dentistry, New York University, New York, NY, United States
| | - John C Dolan
- Bluestone Center for Clinical Research, New York University, New York, NY, United States
| | - Susanna Wang
- College of Dentistry, New York University, New York, NY, United States
| | - Hyesung Kim
- Bluestone Center for Clinical Research, New York University, New York, NY, United States
| | - Donna G Albertson
- Bluestone Center for Clinical Research, New York University, New York, NY, United States
| | - Brian L Schmidt
- Bluestone Center for Clinical Research, New York University, New York, NY, United States
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50
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Amin FM, Aristeidou S, Baraldi C, Czapinska-Ciepiela EK, Ariadni DD, Di Lenola D, Fenech C, Kampouris K, Karagiorgis G, Braschinsky M, Linde M, European Headache Federation School of Advanced Studies (EHF-SAS). The association between migraine and physical exercise. J Headache Pain 2018; 19:83. [PMID: 30203180 PMCID: PMC6134860 DOI: 10.1186/s10194-018-0902-y] [Citation(s) in RCA: 106] [Impact Index Per Article: 15.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/19/2018] [Accepted: 08/05/2018] [Indexed: 01/03/2023] Open
Abstract
BACKGROUND There is an unmet need of pharmacological and non-pharmacological treatment options for migraine patients. Exercise can be used in the treatment of several pain conditions, including. However, what exact role exercise plays in migraine prevention is unclear. Here, we review the associations between physical exercise and migraine from an epidemiological, therapeutical and pathophysiological perspective. METHODS The review was based on a primary literature search on the PubMed using the search terms "migraine and exercise". RESULTS Low levels of physical exercise and high frequency of migraine has been reported in several large population-based studies. In experimental studies exercise has been reported as a trigger factor for migraine as well as migraine prophylaxis. Possible mechanisms for how exercise may trigger migraine attacks, include acute release of neuropeptides such as calcitonin gene-related peptide or alternation of hypocretin or lactate metabolism. Mechanisms for migraine prevention by exercise may include increased beta-endorphin, endocannabinoid and brain-derived neurotrophic factor levers in plasma after exercise. CONCLUSION In conclusion, it seems that although exercise can trigger migraine attacks, regular exercise may have prophylactic effect on migraine frequency. This is most likely due to an altered migraine triggering threshold in persons who exercise regularly. However, the frequency and intensity of exercise that is required is still an open question, which should be addressed in future studies to delineate an evidence-based exercise program to prevent migraine in sufferers.
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Affiliation(s)
- Faisal Mohammad Amin
- Department of Neurology, Danish Headache Center, Rigshospitalet Glostrup, University of Copenhagen, Valdemar Hansens Vej 5, 2600 Glostrup, Denmark
| | - Stavroula Aristeidou
- 1st Neurology of Department, Eginition Hospital, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece
| | - Carlo Baraldi
- Department of Diagnostic, Medical Toxicology, Headache and Drug Abuse Research Center, Clinical and Public Health Medicine, University of Modena and Reggio Emilia, Modena, Italy
| | | | - Daponte D. Ariadni
- 1st Neurology of Department, Eginition Hospital, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece
| | - Davide Di Lenola
- Department of Medico-Surgical Sciences and Biotechnologies, Sapienza University of Rome Polo Pontino, Latina, Italy
| | | | - Konstantinos Kampouris
- 1st Neurology of Department, Eginition Hospital, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece
| | - Giorgos Karagiorgis
- 1st Neurology of Department, Eginition Hospital, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece
| | - Mark Braschinsky
- Neurology Clinic’s Headache Clinic, Tartu University Clinics, Tartu, Estonia
| | - Mattias Linde
- Department of Neuromedicine and Movement Science, NTNU Norwegian University of Science and Technology, Trondheim, Norway
- Norwegian Advisory Unit on Headache, St Olavs University Hospital, Trondheim, Norway
| | - European Headache Federation School of Advanced Studies (EHF-SAS)
- Department of Neurology, Danish Headache Center, Rigshospitalet Glostrup, University of Copenhagen, Valdemar Hansens Vej 5, 2600 Glostrup, Denmark
- 1st Neurology of Department, Eginition Hospital, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece
- Department of Diagnostic, Medical Toxicology, Headache and Drug Abuse Research Center, Clinical and Public Health Medicine, University of Modena and Reggio Emilia, Modena, Italy
- Epilepsy and Migraine Treatment Centre, Kraków, Poland
- Department of Medico-Surgical Sciences and Biotechnologies, Sapienza University of Rome Polo Pontino, Latina, Italy
- Headache Centre, Guys and St Thomas NHS Trust, London, UK
- Neurology Clinic’s Headache Clinic, Tartu University Clinics, Tartu, Estonia
- Department of Neuromedicine and Movement Science, NTNU Norwegian University of Science and Technology, Trondheim, Norway
- Norwegian Advisory Unit on Headache, St Olavs University Hospital, Trondheim, Norway
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