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Kouri M, Adamo D, Vardas E, Georgaki M, Canfora F, Mignogna MD, Nikitakis N. Small Fiber Neuropathy in Burning Mouth Syndrome: A Systematic Review. Int J Mol Sci 2024; 25:11442. [PMID: 39518993 PMCID: PMC11546372 DOI: 10.3390/ijms252111442] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/13/2024] [Revised: 10/17/2024] [Accepted: 10/22/2024] [Indexed: 11/16/2024] Open
Abstract
Burning mouth syndrome (BMS) is a chronic idiopathic orofacial pain disorder, characterized by persistent burning sensations and pain without clear pathological causes. Recent research suggests that small fiber neuropathy (SFN) may play a significant role in the neuropathic pain and sensory disturbances associated with BMS. Following PRISMA guidelines, this systematic review aims to evaluate and synthesize current evidence supporting SFN's involvement in BMS. The protocol is registered in PROSPERO (CRD42024555839). The results show eight studies reported reductions in nerve fiber density in tongue biopsies (ranging from 30% to 60%), along with morphological changes indicative of small fiber damage. Additionally, an increase in TRPV1-positive, NGF-positive, and P2X3-positive fibers, overexpression of Nav1.7, and slight underexpression of Nav1.9 mRNA were observed in BMS patients. Quantitative Sensory Testing in seven studies revealed sensory abnormalities such as reduced cool detection and cold pain thresholds. Blink reflex and corneal confocal microscopy also indicated peripheral and central small fiber damage, along with increased artemin mRNA expression. The evidence strongly supports SFN as a key factor in the pathophysiology of BMS, particularly due to reductions in nerve fiber density and altered sensory thresholds. However, variability across studies highlights the need for larger, standardized research to establish causal relationships and guide therapeutic strategies.
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Affiliation(s)
- Maria Kouri
- Department of Oral Medicine & Pathology and Hospital Dentistry, School of Dentistry, National and Kapodistrian University of Athens, 15772 Athens, Greece
| | - Daniela Adamo
- Department of Neurosciences, Reproductive and Odontostomatological Sciences, Federico II University of Naples, 80131 Naples, Italy
| | - Emmanouil Vardas
- Department of Oral Medicine & Pathology and Hospital Dentistry, School of Dentistry, National and Kapodistrian University of Athens, 15772 Athens, Greece
| | - Maria Georgaki
- Department of Oral Medicine & Pathology and Hospital Dentistry, School of Dentistry, National and Kapodistrian University of Athens, 15772 Athens, Greece
| | - Federica Canfora
- Department of Neurosciences, Reproductive and Odontostomatological Sciences, Federico II University of Naples, 80131 Naples, Italy
| | - Michele Davide Mignogna
- Department of Neurosciences, Reproductive and Odontostomatological Sciences, Federico II University of Naples, 80131 Naples, Italy
| | - Nikolaos Nikitakis
- Department of Oral Medicine & Pathology and Hospital Dentistry, School of Dentistry, National and Kapodistrian University of Athens, 15772 Athens, Greece
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Paolla Raimundo E Silva J, Raimundo E Silva JP, Silva Vasconcelos PG, Targino Campos L, de Medeiros Gomes J, Tolentino Leite Filho M, Menezes RPBD, Scotti MT, Tavares JF, Cristina Barbosa Silva A, Costa EMMDB. The potential of Acmella oleracea as a nutraceutical source for the symptomatic treatment of Burning Mouth Syndrome. Nat Prod Res 2024; 38:3535-3541. [PMID: 37671677 DOI: 10.1080/14786419.2023.2253974] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/16/2023] [Revised: 08/07/2023] [Accepted: 08/28/2023] [Indexed: 09/07/2023]
Abstract
This study analysed the phytochemical profile of Acmella oleracea extract and the molecular interactions of its main compounds with TRPV1 and CB2, target receptors in the Burning Mouth Syndrome (BMS) pathogenesis. The phytochemical profile of A. oleracea's floral buds extract treated with activated charcoal (TCEE) was analysed by High-Performance Liquid Chromatography (HPLC) coupled to Mass Spectrometry (LC-MS). The quantification of spilanthol was analysed by HPLC coupled to a Diode-Array Detector (HPLC-DAD). The phytochemical analysis revealed the presence of nine alkylamides and phenolic compounds. The TCEE showed a significant increase in spilanthol content compared to the crude extract (CEE), going from 28.33 mg/g to 117.96 mg/g. The molecular docking indicated a behaviour of the alkylamides as partial TRPV1 agonists and CB2 agonists and, for the first time, indicates the action of these compounds in the symptomatic management of BMS.
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Affiliation(s)
| | | | | | - Letícia Targino Campos
- Postgraduate Programme in Dentistry, State University of Paraiba, Campina Grande, Brazil
| | - Juliana de Medeiros Gomes
- Postgraduate Programme in Natural and Synthetic Bioactive Products, Federal University of Paraiba, João Pessoa, Brazil
| | | | | | - Marcus Tullius Scotti
- Postgraduate Programme in Natural and Synthetic Bioactive Products, Federal University of Paraiba, João Pessoa, Brazil
| | - Josean Fechine Tavares
- Postgraduate Programme in Natural and Synthetic Bioactive Products, Federal University of Paraiba, João Pessoa, Brazil
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Alajbeg IZ, Vrbanovic E, Alajbeg I, Orabovic I, Naka K, Mrla A, Boucher Y. Time-course of pain and salivary opiorphin release in response to oral capsaicin differ in burning mouth syndrome patients, temporomandibular disorders patients and control subjects. Clin Oral Investig 2024; 28:246. [PMID: 38589630 DOI: 10.1007/s00784-024-05653-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/11/2023] [Accepted: 04/03/2024] [Indexed: 04/10/2024]
Abstract
OBJECTIVES Opiorphin is an analgesic peptide released by salivary glands and capsaicin an agonist of TRPV1 receptors eliciting burning sensations. The primary objective of this study was to assess opiorphin release after stimulation of the tongue by capsaicin (STC). The secondary objectives were to compare opiorphin release after STC in 3 groups of subjects [healthy (CTRL), Burning Mouth Syndrome (BMS), painful Temporomandibular disorders (TMDp)] and pain evoked by STC in these 3 groups. MATERIALS AND METHODS Salivary opiorphin was assessed with high-performance liquid chromatography at 3 different time points (baseline, after 5 min and 20 min of STC). Pain was self-reported on a (0-10) numeric rating scale. RESULTS Three groups (N = 16) of adults were recruited at the Clinical Hospital Centre and School of Dental Medicine in Zagreb. Opiorphin levels were higher (1) in TMDp compared to CTRL in 1st (2.23 ± 1.72 pg/ul vs. 0.67 ± 0.44 pg/ul, p = 0.002) and 3rd sampling (2.44 ± 2.01 pg/ul vs. 0.74 ± 0.52 pg/ul, p = 0.020) and (2) within BMS group at 3rd sampling vs. baseline (p < 0.025). Pain scores were higher in BMS compared to TMDp (p < 0.025) and CTRL (p < 0.025). CONCLUSION This study evidenced (1) a differential basal amount of opiorphin in two pain conditions and control subjects (2) a differential kinetic of release of opiorphin after STC in CTRL, BMS and TMDp (3) a differential pain perception after STC in BMS and TMDp vs. CTRL, which can provide a readout for animal models. CLINICAL RELEVANCE The specific regulation of opiorphin release in patients with orofacial painful conditions provides valuable insights for clinicians and researchers in physiology and pathology and encourages further research in this area. TRIAL REGISTRATION ClinicalTrials.gov NCT04694274. Registered on 01/05/2021.
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Affiliation(s)
- Iva Z Alajbeg
- Department of Removable Prosthodontics, University of Zagreb School of Dental Medicine, University of Zagreb, Zagreb, 10000, Croatia.
- Department of Dental Medicine, Clinical Hospital Centre Zagreb, Zagreb, 10000, Croatia.
| | - Ema Vrbanovic
- Department of Removable Prosthodontics, University of Zagreb School of Dental Medicine, University of Zagreb, Zagreb, 10000, Croatia
| | - Ivan Alajbeg
- Department of Oral Medicine, University of Zagreb School of Dental Medicine, University of Zagreb, Zagreb, 10000, Croatia
- Department of Dental Medicine, Clinical Hospital Centre Zagreb, Zagreb, 10000, Croatia
| | - Ivan Orabovic
- Department of Removable Prosthodontics, University of Zagreb School of Dental Medicine, University of Zagreb, Zagreb, 10000, Croatia
| | - Klara Naka
- Department of Removable Prosthodontics, University of Zagreb School of Dental Medicine, University of Zagreb, Zagreb, 10000, Croatia
| | - Antonija Mrla
- Department of Removable Prosthodontics, University of Zagreb School of Dental Medicine, University of Zagreb, Zagreb, 10000, Croatia
| | - Yves Boucher
- Laboratoire de Neurobiologie Orofaciale, UFR Odontologie, Université Paris Cité, Paris, 75006, France
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Gunduz A, Valls-Solé J, Serranová T, Coppola G, Kofler M, Jääskeläinen SK. The blink reflex and its modulation - Part 2: Pathophysiology and clinical utility. Clin Neurophysiol 2024; 160:75-94. [PMID: 38412746 DOI: 10.1016/j.clinph.2024.02.006] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/09/2023] [Revised: 12/30/2023] [Accepted: 02/06/2024] [Indexed: 02/29/2024]
Abstract
The blink reflex (BR) is integrated at the brainstem; however, it is modulated by inputs from various structures such as the striatum, globus pallidus, substantia nigra, and nucleus raphe magnus but also from afferent input from the peripheral nervous system. Therefore, it provides information about the pathophysiology of numerous peripheral and central nervous system disorders. The BR is a valuable tool for studying the integrity of the trigemino-facial system, the relevant brainstem nuclei, and circuits. At the same time, some neurophysiological techniques applying the BR may indicate abnormalities involving structures rostral to the brainstem that modulate or control the BR circuits. This is a state-of-the-art review of the clinical application of BR modulation; physiology is reviewed in part 1. In this review, we aim to present the role of the BR and techniques related to its modulation in understanding pathophysiological mechanisms of motor control and pain disorders, in which these techniques are diagnostically helpful. Furthermore, some BR techniques may have a predictive value or serve as a basis for follow-up evaluation. BR testing may benefit in the diagnosis of hemifacial spasm, dystonia, functional movement disorders, migraine, orofacial pain, and psychiatric disorders. Although the abnormalities in the integrity of the BR pathway itself may provide information about trigeminal or facial nerve disorders, alterations in BR excitability are found in several disease conditions. BR excitability studies are suitable for understanding the common pathophysiological mechanisms behind various clinical entities, elucidating alterations in top-down inhibitory systems, and allowing for follow-up and quantitation of many neurological syndromes.
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Affiliation(s)
- Aysegul Gunduz
- Istanbul University-Cerrahpasa, Cerrahpasa Faculty of Medicine, Department of Neurology, Division of Neurophysiology, Istanbul, Turkey.
| | - Josep Valls-Solé
- IDIBAPS. Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Villarroel 170 08024, Barcelona, Spain.
| | - Tereza Serranová
- Department of Neurology and Center of Clinical Neuroscience, Charles University, Prague 1st Faculty of Medicine and General University Hospital, Prague, Kateřinská 30, 12800 Prague 2, Czech Republic.
| | - Gianluca Coppola
- Department of Medico-Surgical Sciences and Biotechnologies, Sapienza University of Rome Polo Pontino ICOT, via Franco Faggiana 1668 04100, Latina, Italy.
| | - Markus Kofler
- Department of Neurology, Hochzirl Hospital, A-6170 Zirl, Austria.
| | - Satu K Jääskeläinen
- Department of Clinical Neurophysiology, Division of Medical Imaging, Turku University Hospital and University of Turku, Postal Box 52, FIN 20521 Turku, Finland.
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Zhao H, Ran S, Gan K, Du Y, Li W. Pain sensitivity and quality of life of patients with burning mouth syndrome: a preliminary study in a Chinese population. BMC Oral Health 2023; 23:951. [PMID: 38041054 PMCID: PMC10693025 DOI: 10.1186/s12903-023-03689-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/11/2023] [Accepted: 11/21/2023] [Indexed: 12/03/2023] Open
Abstract
BACKGROUND Burning mouth syndrome (BMS) is an oral-facial pain disorder involving the central and peripheral nervous systems, but the evidence for altered pain sensitivity remains inconclusive. The aim of this study was to investigate pain sensitivity and oral health-related quality of life (OHRQoL) in patients with BMS and to assess the relationship between them. METHODS Fifty Chinese patients with BMS (57.82 ± 11.2 years) and fifty age- and gender-matched healthy subjects (55.64 ± 10.1 years) participated in the study. The Pain Sensitivity Questionnaire (PSQ) was used to assess participants' pain sensitivity. The Oral Health Impact Profile (OHIP-14) was used to evaluate participants' OHRQoL. RESULTS The PSQ total score (p = 0.009), the PSQ minor score (p = 0.003) and the OHIP-14 score (p<0.05) of patients with BMS were significantly higher than those of the healthy subjects. Simple linear regression showed that the PSQ minor score was significantly associated with the OHIP-14 score in patients with BMS (β = 0.338, p = 0.016). CONCLUSION Patients with BMS have higher pain sensitivity than healthy subjects. Reducing pain sensitivity might help to improve the quality of life of patients with BMS.
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Affiliation(s)
- Hongsen Zhao
- Department of Stomatology, The First Affiliated Hospital of Zhengzhou University, No. 1 Jianshe East Road, Zhengzhou City, 450052, China.
| | - Shujun Ran
- National Clinical Research Center for Oral Diseases, Shanghai, China
| | - Kang Gan
- Department of Stomatology, The First Affiliated Hospital of Zhengzhou University, No. 1 Jianshe East Road, Zhengzhou City, 450052, China
| | - Yajing Du
- Department of Stomatology, The First Affiliated Hospital of Zhengzhou University, No. 1 Jianshe East Road, Zhengzhou City, 450052, China
| | - Wenlu Li
- Department of Stomatology, The First Affiliated Hospital of Zhengzhou University, No. 1 Jianshe East Road, Zhengzhou City, 450052, China
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Porporatti AL, Schroder ÂGD, Lebel A, Moreau N, Misery L, Alajbeg I, Braud A, Boucher Y. Is burning mouth syndrome associated with stress? A meta-analysis. J Oral Rehabil 2023; 50:1279-1315. [PMID: 37332081 DOI: 10.1111/joor.13536] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/08/2022] [Revised: 04/04/2023] [Accepted: 06/10/2023] [Indexed: 06/20/2023]
Abstract
BACKGROUND Some studies have shown burning mouth syndrome (BMS) as comorbid psychosocial and psychiatric disorders, and as well, pointed at stress as a major risk factor. OBJECTIVE The aim of this meta-analysis was to answer the following question: 'Is there an association between BMS and stress, compared to healthy controls?' METHODS Two reviewers searched for the effect of stress in BMS and published on five main databases and three from the grey literature. Various questionnaires and biomarkers were analysed. Of the 2489 selected articles, 30 met the inclusion criteria. Studies englobed questionnaires, such as Perceived Stress Questionnaire, Lipp Stress Symptoms Inventory, Holmes-Rahe scale, Depression, Anxiety, and Stress Scale (DASS-21), Recent Experience Test; and various biomarkers, such as cortisol, opiorphin, IgA, α-amylase and interleukins. RESULTS In all studies with questionnaires, stress was significantly increased in the BMS group vs. control. Patients with BMS presented 25.73% higher cortisol levels, 28.17% higher IgA levels and 40.62% higher α-amylase levels than controls. Meta-analysis found that BMS subjects presented 3.01 nmoL/L [0.53; 5.50] higher cortisol levels, 84.35 kU/L [15.00; 153.71] higher α-amylase levels, 29.25 mg/mL [9.86; 48.64] higher IgA levels and 258.59 pg/mL [59.24; 457.94] higher IL-8 levels than control. No differences were found for opiorphin concentration in ng/mL [-0.96; 2.53]. For interleukins, no differences were founded for IL-1 β, IL-2, IL-4, IL-6, IL-8, IL-10 and TNF-α. CONCLUSION Based on the available evidence, this meta-analysis suggests more stress factors in questionnaire-based studies, and higher levels of cortisol, α-amylase, IgA and IL-8 biomarkers in BMS subjects than controls.
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Affiliation(s)
- André Luís Porporatti
- Laboratoire de Neurobiologie Oro-Faciale (EA 7543), Université Paris Cité, France and GHPS Assistance Publique Hôpitaux de Paris, Paris, France
| | | | - Ashley Lebel
- Laboratoire de Neurobiologie OroFaciale, Université Paris Cité, France and GHPS Assistance Publique Hôpitaux de Paris, Paris, France
| | - Nathan Moreau
- Laboratoire de Neurobiologie Oro-Faciale (EA 7543), Université Paris Cité and Hôpital Bretonneau (AP-HP), Paris, France
| | | | | | - Adeline Braud
- Laboratoire de Neurobiologie Oro-Faciale (EA 7543), Université Paris Cité, France and GHPS Assistance Publique Hôpitaux de Paris, Paris, France
| | - Yves Boucher
- Laboratoire de Neurobiologie Oro-Faciale (EA 7543), Université Paris Cité, France and GHPS Assistance Publique Hôpitaux de Paris, Paris, France
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O G, Balasubramaniam R, Klasser GD. Burning mouth disorder and Parkinson's disease: A scoping review of the literature. J Oral Rehabil 2023; 50:488-500. [PMID: 36855821 DOI: 10.1111/joor.13443] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/25/2022] [Revised: 02/13/2023] [Accepted: 02/20/2023] [Indexed: 03/02/2023]
Abstract
BACKGROUND Burning mouth disorder (BMD) is a complex medical condition characterized by a burning sensation in the mouth of fluctuating intensity. BMD is considered a diagnosis of exclusion, as oral burning can occur secondary to local or systemic conditions. Parkinson's disease (PD) is one such condition. OBJECTIVE To provide a scoping review of the literature by assessing all articles written in English that investigated the relationship between BMD and PD. MATERIALS AND METHODS Various databases (PubMed, Ovid, Web of Science, Science Direct and Scopus) and a search platform (EBSCOhost) were searched following similar investigative approaches. Duplicates were removed and reference lists of original studies were scrutinized for additional articles. Any decision about the inclusion/exclusion in the review was by consensus among the co-authors. RESULTS Twenty-five original articles and one supplemental article were included in the final review, of which 13 met the inclusion criteria. These were further divided into five categories based on the study design/article, which included Prevalence studies (n = 6), Letter to the editor (n = 1), Incidence study (n = 1), Case reports (n = 2) and Experimental studies (n = 3). Strongest data was provided by epidemiological studies, which suggest BMD and PD are poorly associated. CONCLUSIONS A scoping review of the existing literature does not suggest that PD patients are any more at risk of developing BMD compared to the general population. While there may be a link through the dopaminergic system as determined by imaging studies, it is unlikely that the pathogenesis of PD disease shares significant commonality with BMD.
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Affiliation(s)
- Guru O
- UWA Dental School, University of Western Australia, Crawley, Western Australia, Australia
| | - Ramesh Balasubramaniam
- UWA Dental School, University of Western Australia, Crawley, Western Australia, Australia
| | - Gary D Klasser
- Department of Diagnostic Sciences, School of Dentistry, Louisiana State University Health Sciences Center, New Orleans, Louisiana, USA
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Santonocito S, Donzella M, Venezia P, Nicolosi G, Mauceri R, Isola G. Orofacial Pain Management: An Overview of the Potential Benefits of Palmitoylethanolamide and Other Natural Agents. Pharmaceutics 2023; 15:pharmaceutics15041193. [PMID: 37111679 PMCID: PMC10142272 DOI: 10.3390/pharmaceutics15041193] [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: 01/04/2023] [Revised: 04/03/2023] [Accepted: 04/07/2023] [Indexed: 04/29/2023] Open
Abstract
Pain is the most common symptom that dentists are confronted with, whether acute (pulpitis, acute periodontitis, post-surgery, etc.) or chronic diseases, such as periodontitis, muscle pain, temporomandibular joint (TMJ) disorders, burning mouth syndrome (BMS), oral lichen planus (OLP) and others. The success of therapy depends on the reduction in and management of pain through specific drugs, hence the need to analyze new pain medications with specific activity, which are suitable for long-term use, with a low risk of side effects and interactions with other drugs, and capable of leading to a reduction in orofacial pain. Palmitoylethanolamide (PEA) is a bioactive lipid mediator, which is synthesized in all tissues of the body as a protective pro-homeostatic response to tissue damage and has aroused considerable interest in the dental field due to its anti-inflammatory, analgesic, antimicrobial, antipyretic, antiepileptic, immunomodulatory and neuroprotective activities. It has been observed that PEA could play a role in the management of the pain of orofacial origin, including BMS, OLP, periodontal disease, tongue a la carte and temporomandibular disorders (TMDs), as well as in the treatment of postoperative pain. However, actual clinical data on the use of PEA in the clinical management of patients with orofacial pain are still lacking. Therefore, the main objective of the present study is to provide an overview of orofacial pain in its many manifestations and an updated analysis of the molecular pain-relieving and anti-inflammatory properties of PEA to understand its beneficial effects in the management of patients with orofacial pain, both neuropathic and nociceptive in nature. The aim is also to direct research toward the testing and use of other natural agents that have already been shown to have anti-inflammatory, antioxidant and pain-relieving actions and could offer important support in the treatment of orofacial pain.
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Affiliation(s)
- Simona Santonocito
- Department of General Surgery and Surgical-Medical Specialties, School of Dentistry, University of Catania, 95124 Catania, Italy
| | - Martina Donzella
- Department of General Surgery and Surgical-Medical Specialties, School of Dentistry, University of Catania, 95124 Catania, Italy
| | - Pietro Venezia
- Department of General Surgery and Surgical-Medical Specialties, School of Dentistry, University of Catania, 95124 Catania, Italy
| | - Giada Nicolosi
- Department of General Surgery and Surgical-Medical Specialties, School of Dentistry, University of Catania, 95124 Catania, Italy
| | - Rodolfo Mauceri
- Department of Surgical, Oncological, and Oral Sciences, University of Palermo, 90127 Palermo, Italy
| | - Gaetano Isola
- Department of General Surgery and Surgical-Medical Specialties, School of Dentistry, University of Catania, 95124 Catania, Italy
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Dagnino APA, Campos MM. Chronic Pain in the Elderly: Mechanisms and Perspectives. Front Hum Neurosci 2022; 16:736688. [PMID: 35308613 PMCID: PMC8928105 DOI: 10.3389/fnhum.2022.736688] [Citation(s) in RCA: 65] [Impact Index Per Article: 21.7] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/05/2021] [Accepted: 01/27/2022] [Indexed: 12/12/2022] Open
Abstract
Chronic pain affects a large part of the population causing functional disability, being often associated with coexisting psychological disorders, such as depression and anxiety, besides cognitive deficits, and sleep disturbance. The world elderly population has been growing over the last decades and the negative consequences of chronic pain for these individuals represent a current clinical challenge. The main painful complaints in the elderly are related to neurodegenerative and musculoskeletal conditions, peripheral vascular diseases, arthritis, and osteoarthritis, contributing toward poorly life quality, social isolation, impaired physical activity, and dependence to carry out daily activities. Organ dysfunction and other existing diseases can significantly affect the perception and responses to chronic pain in this group. It has been proposed that elderly people have an altered pain experience, with changes in pain processing mechanisms, which might be associated with the degeneration of circuits that modulate the descending inhibitory pathways of pain. Aging has also been linked to an increase in the pain threshold, a decline of painful sensations, and a decrease in pain tolerance. Still, elderly patients with chronic pain show an increased risk for dementia and cognitive impairment. The present review article is aimed to provide the state-of-art of pre-clinical and clinical research about chronic pain in elderly, emphasizing the altered mechanisms, comorbidities, challenges, and potential therapeutic alternatives.
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Affiliation(s)
- Ana P. A. Dagnino
- Programa de Pós-graduação em Medicina e Ciências da Saúde, Escola de Medicina, Pontifícia Universidade Católica do Rio Grande do Sul, Porto Alegre, Brazil
- Centro de Pesquisa em Toxicologia e Farmacologia, Escola de Ciências da Saúde e da Vida, Pontifícia Universidade Católica do Rio Grande do Sul, Porto Alegre, Brazil
| | - Maria M. Campos
- Programa de Pós-graduação em Medicina e Ciências da Saúde, Escola de Medicina, Pontifícia Universidade Católica do Rio Grande do Sul, Porto Alegre, Brazil
- Centro de Pesquisa em Toxicologia e Farmacologia, Escola de Ciências da Saúde e da Vida, Pontifícia Universidade Católica do Rio Grande do Sul, Porto Alegre, Brazil
- Programa de Pós-graduação em Odontologia, Escola de Ciências da Saúde e da Vida, Pontifícia Universidade Católica do Rio Grande do Sul, Porto Alegre, Brazil
- *Correspondence: Maria M. Campos, ,
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Camolesi GCV, Marichalar-Mendía X, Padín-Iruegas ME, Spanemberg JC, López-López J, Blanco-Carrión A, Gándara-Vila P, Gallas-Torreira M, Pérez-Sayáns M. Efficacy of photobiomodulation in reducing pain and improving the quality of life in patients with idiopathic burning mouth syndrome. A systematic review and meta-analysis. Lasers Med Sci 2022; 37:2123-2133. [PMID: 35122543 PMCID: PMC9148274 DOI: 10.1007/s10103-022-03518-y] [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: 12/21/2021] [Accepted: 01/28/2022] [Indexed: 12/28/2022]
Abstract
Burning mouth syndrome is a chronic condition, which is characterised by a burning sensation or pain in the mucosa of the oral cavity. Treatment options include antidepressants, antipsychotics, anticonvulsants, analgesics, hormone replacement therapies and more recently photobiomodulation. This study aims to perform a systematic review with meta-analysis in order to determine the effect of photobiomodulation on pain relief and the oral health-related quality of life associated with this condition. A bibliographical search of the Pubmed, Embase, Web of Science and Scopus databases was conducted. Only randomised clinical trials were included. Pain and quality of life were calculated as mean difference and pooled at different treatment points (baseline = T0 and final time point = Tf) and laser modality. From a total of 103 records, 7 articles were retrieved for inclusion. PBM group had a greater decrease in pain than control group at Tf with a mean difference = − 2.536 (IC 95% − 3.662 to − 1.410; I2 = 85.33%, p < 0.001). An improvement in oral health-related quality of life was observed in both groups, although this was more significant in the photobiomodulation group mean difference = − 5.148 (IC 95% − 8.576 to − 1.719; I2 = 84.91%, p = 0.003). For the red laser, a greater improvement than infrared was observed, in pain, mean difference = − 2.498 (IC 95% − 3.942 to − 1.053; I2 = 79.93%, p < 0.001), and in quality of life, mean difference = − 8.144 (IC 95% − 12.082 to − 4.206; I2 = 64.22%, p = 0.027). Photobiomodulation, in particular, red laser protocols, resulted in improvement in pain and in quality of life of burning mouth syndrome patients.
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Affiliation(s)
- Gisela Cristina Vianna Camolesi
- Faculty of Medicine and Dentistry, University of Santiago de Compostela, Santiago de Compostela C.P, Entrerríos s/n, 15782, Galicia, Spain.,Oral Medicine, Oral Surgery and Implantology Unit (MedOralRes), Faculty of Medicine and Dentistry, University of Santiago de Compostela, Santiago de Compostela C.P, Entrerríos s/n, 15782, Galicia, Spain
| | - Xabier Marichalar-Mendía
- Nursing I Department, University of the Basque Country (UPV/EHU), C.P. 48940, Leioa, Bizkaia, Spain
| | - Maria Elena Padín-Iruegas
- Human Anatomy and Embryology Area, Department of Functional Biology and Health Sciences, Faculty of Physiotherapy, Pontevedra, Spain.
| | - Juliana Cassol Spanemberg
- Oral Medicine and Public Health, Faculty of Dentistry, Universidad Fernando Pessoa-Canarias, Santa María de Guía, Calle de la Juventud s/n, C.P. 35450, Gran Canaria, Spain
| | - Jose López-López
- Department of Odontostomatology, Faculty of Medicine and Health Sciences, School of Dentistry, University of Barcelona//Oral Health and Masticatory System Group-IDIBELL, C.P. 08907, Barcelona, Cataluña, Spain
| | - Andrés Blanco-Carrión
- Oral Medicine, Oral Surgery and Implantology Unit (MedOralRes), Faculty of Medicine and Dentistry, University of Santiago de Compostela, Santiago de Compostela C.P, Entrerríos s/n, 15782, Galicia, Spain.,Health Research Institute of Santiago (IDIS) (ORALRES), Santiago de Compostela, Spain
| | - Pilar Gándara-Vila
- Oral Medicine, Oral Surgery and Implantology Unit (MedOralRes), Faculty of Medicine and Dentistry, University of Santiago de Compostela, Santiago de Compostela C.P, Entrerríos s/n, 15782, Galicia, Spain.,Health Research Institute of Santiago (IDIS) (ORALRES), Santiago de Compostela, Spain
| | - Mercedes Gallas-Torreira
- Oral Medicine, Oral Surgery and Implantology Unit (MedOralRes), Faculty of Medicine and Dentistry, University of Santiago de Compostela, Santiago de Compostela C.P, Entrerríos s/n, 15782, Galicia, Spain.,Health Research Institute of Santiago (IDIS) (ORALRES), Santiago de Compostela, Spain
| | - Mario Pérez-Sayáns
- Oral Medicine, Oral Surgery and Implantology Unit (MedOralRes), Faculty of Medicine and Dentistry, University of Santiago de Compostela, Santiago de Compostela C.P, Entrerríos s/n, 15782, Galicia, Spain.,Health Research Institute of Santiago (IDIS) (ORALRES), Santiago de Compostela, Spain
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11
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Payano Sosa JS, Da Silva JT, Burrowes SAB, Yoo SY, Keaser ML, Meiller TF, Seminowicz DA. Time of Day Influences Psychophysical Measures in Women With Burning Mouth Syndrome. Front Neurosci 2021; 15:698164. [PMID: 34658757 PMCID: PMC8519262 DOI: 10.3389/fnins.2021.698164] [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: 04/20/2021] [Accepted: 09/02/2021] [Indexed: 11/13/2022] Open
Abstract
Burning mouth syndrome (BMS) is a chronic orofacial pain condition that mainly affects postmenopausal women. BMS type I patients report little to no spontaneous pain in the morning and increases in pain through the day, peaking in the afternoon. Quantitative sensory testing (QST) findings from BMS type 1 patients are inconsistent as they fail to capture this temporal variation. We examined how QST in BMS type 1 (n = 18) compared to healthy participants (n = 33) was affected by time of day. QST of the face and forearm included warmth detection threshold (WDT), cold detection threshold (CDT), and heat pain thresholds (HPT), ratings of suprathreshold heat, and pressure pain thresholds (PPT), and was performed twice: once in the morning and once in the afternoon. Compared to healthy participants, BMS patients had higher pain sensitivity to phasic heat stimuli at most temperatures (35°C U = 126.5, p = 0.0006, 39°C U = 186.5, p = 0.0386, 41°C U = 187.5, p = 0.0412, 43°C U = 171, p = 0.0167, 45°C U = 168.5, p = 0.0146) on the forearm, but no differences in pain thresholds (HPT and PPT) regardless of time of day or body area tested. BMS patients had higher WDT (U = 123, p = 0.0172), and lower CDT (U = 98, p = 0.0021) of the forearm and lower WDT of the face (U = 55, p = 0.0494). The differences in forearm WDT (U = 71.5, p = 0.0113) and CDT (U = 70, p = 0.0096) were most pronounced in the morning. In summary, BMS type I patients had increased pain sensitivity on the forearm, but no differences in pain thresholds on the face or forearm. Patients also showed altered thermal sensitivity, which depended on body area tested (heightened in the orofacial region but blunted on the forearm), and was more pronounced in the morning plausibly due to hypervigilance.
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Affiliation(s)
- Janell S Payano Sosa
- Program in Neuroscience, University of Maryland, Baltimore, Baltimore, MD, United States.,Department of Neural and Pain Sciences, University of Maryland School of Dentistry, Baltimore, MD, United States.,Center to Advance Chronic Pain Research, University of Maryland, Baltimore, Baltimore, MD, United States
| | - Joyce T Da Silva
- Department of Neural and Pain Sciences, University of Maryland School of Dentistry, Baltimore, MD, United States.,Center to Advance Chronic Pain Research, University of Maryland, Baltimore, Baltimore, MD, United States.,Department of Psychiatry, School of Medicine, Johns Hopkins University, Baltimore, MD, United States
| | - Shana A B Burrowes
- Section of Infectious Diseases, Department of Medicine, Boston University School of Medicine, Boston, MA, United States
| | - Soo Y Yoo
- Montefiore Medical Center, The Bronx, NY, United States
| | - Michael L Keaser
- Department of Neural and Pain Sciences, University of Maryland School of Dentistry, Baltimore, MD, United States.,Center to Advance Chronic Pain Research, University of Maryland, Baltimore, Baltimore, MD, United States
| | - Timothy F Meiller
- Oncology and Diagnostic Sciences, University of Maryland School of Dentistry, Baltimore, MD, United States
| | - David A Seminowicz
- Department of Neural and Pain Sciences, University of Maryland School of Dentistry, Baltimore, MD, United States.,Center to Advance Chronic Pain Research, University of Maryland, Baltimore, Baltimore, MD, United States
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12
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Orliaguet M, Misery L. Neuropathic and Psychogenic Components of Burning Mouth Syndrome: A Systematic Review. Biomolecules 2021; 11:biom11081237. [PMID: 34439903 PMCID: PMC8393188 DOI: 10.3390/biom11081237] [Citation(s) in RCA: 24] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/29/2021] [Revised: 08/16/2021] [Accepted: 08/17/2021] [Indexed: 12/27/2022] Open
Abstract
The pathophysiology of primary burning mouth syndrome (BMS) has been extensively debated but is poorly understood despite a large number of hypotheses attempting to explain its etiopathogenic mechanisms. The aim of the present work was to systematically review papers that could provide arguments in favour of the neuropathic and psychogenic components of primary BMS for a better understanding of the disease. This systematic review (SR) was registered in PROSPERO (CRD42021224160). The search was limited to articles in English or French from 1990 to 01 December 2020. A total of 113 articles were considered for data extraction. We divided them into four subgroups: pharmacological and nonpharmacological management studies (n = 23); neurophysiological studies (n = 35); biohistopathological studies (n = 25); and questionnaire-based studies (n = 30). Several of these studies have shown neuropathic involvement at various levels of the neuraxis in BMS with the contribution of quantitative sensory testing (QST), functional brain imaging, and biohistopathological or pharmacologic studies. On the other hand, the role of psychological factors in BMS has also been the focus of several studies and has shown a link with psychiatric disorders such as anxiety and/or depression symptoms. Depending on the patient, the neuropathic and psychogenic components may exist simultaneously, with a preponderance of one or the other, or exist individually. These two components cannot be dissociated to define BMS. Consequently, BMS may be considered nociplastic pain.
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Affiliation(s)
- Marie Orliaguet
- LIEN, Department of Oral Surgery, University of Western Brittany, F-29200 Brest, France;
| | - Laurent Misery
- LIEN, Department of Dermatology, University of Western Brittany, F-29200 Brest, France
- Correspondence: ; Tel.: +33-2-9888-3527
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13
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Du QC, Ge YY, Xiao WL, Wang WF. Dopamine agonist responsive burning mouth syndrome: Report of eight cases. World J Clin Cases 2021; 9:6916-6921. [PMID: 34447842 PMCID: PMC8362543 DOI: 10.12998/wjcc.v9.i23.6916] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/22/2021] [Revised: 06/04/2021] [Accepted: 06/15/2021] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Burning mouth syndrome (BMS) is characterized by burning sensation of the oral mucosa. There is a lack of effective treatment. In recent years, a special subtype of BMS has been reported, in which oral burning sensation is alleviated after chewing, speaking, or dopaminergic drug delivery. Currently, there are few reports about the subtype of BMS in China. This study was a retrospective analysis of the clinical data of BMS patients sensitive to dopamine agonist at our hospital, aiming to improve the recognition on this disease.
CASE SUMMARY Eight patients diagnosed with dopamine agonist responsive BMS at the Liaocheng People's Hospital from January 1, 2017 to June 30, 2020 were recruited. The clinical manifestations, treatment, and prognosis were retrospectively analyzed. There were three male and five females in the eight patients. The median age was 56 years (range, 46-65 years). All the eight patients showed burning pain in the mouth. The symptoms were mild in the morning and severe in the evening, and alleviated after chewing, talking, and other oral activities. Four patients were accompanied by restless legs syndrome (RLS). Family history of RLS was positive in two patients. All patients were treated with pramipexol, and symptoms were basically relieved after 2-8 wk.
CONCLUSION Dopamine agonist responsive BMS is a special subtype of BMS, which is alleviated after oral activities. Dopamine receptor agonist is an effective treatment.
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Affiliation(s)
- Qi-Cui Du
- Department of Stomatology, Liaocheng People's Hospital, Liaocheng 252000, Shandong Province, China
| | - Ying-Ying Ge
- School of Stomatology, Qingdao University, Qingdao 266003, Shandong Province, China
| | - Wen-Lin Xiao
- Department of Stomatology, Affiliated Hospital of Qingdao University, Qingdao 266003, Shandong Province, China
| | - Wei-Fei Wang
- Department of Neurology, Liaocheng People's Hospital, Liaocheng 252000, Shandong Province, China
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14
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Alberdi-Navarro J, Aguirre-Urizar JM, Ginestal-Gómez E. Clinical presentation of burning mouth syndrome in patients with oral lichenoid disease. Med Oral Patol Oral Cir Bucal 2020; 25:e805-e809. [PMID: 32851991 PMCID: PMC7648912 DOI: 10.4317/medoral.23812] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/16/2020] [Accepted: 07/10/2020] [Indexed: 11/05/2022] Open
Abstract
BACKGROUND To analyze the presence of burning mouth syndrome (BMS) in a group of patients diagnosed with oral lichenoid disease (OLD). MATERIAL AND METHODS A retrospective study of 217 patients diagnosed with OLD; 158 (72,8%) women and 59 (27,2%) men, with an average age upon diagnosis of 56,4 years (SD 11,88). We carried out a detailed and complete characterization of symptoms, with special emphasis on BMS diagnostic data specified by the International Headache Society. RESULTS Four patients (1.8%) presented with long-term clinical symptoms of burning mouth, indicative of BMS and they fulfilled the IHS 2018 criteria, except for criterion D, i.e."Oral mucosa is of normal appearance". The observed lichenoid mucosal lesions were not considered to be able to account for the reported intraoral pain in any of our patients. Thus neither diagnosis was considered to be exclusive. CONCLUSIONS Patients diagnosed with OLD, and who simultaneously present clinical characteristics of BMS should be studied in detail, in order to evaluate the possibility of both diagnoses concurring.
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Affiliation(s)
- J Alberdi-Navarro
- Oral Medicine and Oral and Maxillofacial Pathology Units Orofacial Pain and Temporomandibular Disorders Unit Dental Clinic Service, Department of Stomatology II School of Medicine and Nursing University of the Basque Country (UPV/EHU) 48940 Leioa, Bizkaia, Spain
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15
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Madariaga VI, Tanaka H, Ernberg M. Psychophysical characterisation of burning mouth syndrome-A systematic review and meta-analysis. J Oral Rehabil 2020; 47:1590-1605. [PMID: 32500929 DOI: 10.1111/joor.13028] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/19/2019] [Revised: 05/20/2020] [Accepted: 05/24/2020] [Indexed: 01/09/2023]
Abstract
BACKGROUND Primary burning mouth syndrome (BMS) is an oro-facial disease with neuropathic characteristics. Psychophysics, such as quantitative sensory testing (QST), is used to sub-classify neuropathic pain syndromes, but their usefulness in characterising BMS is not yet clear. OBJECTIVE The aim of this study was to summarise and to quantitatively and qualitatively analyse the available information about QST findings in BMS, and to reflect on possible mechanisms of disease. METHODS In this systematic review and meta-analysis, different search strategies were used to screen for articles in PubMed, Embase, EBSCOhost, Cochrane Library, Web of Science, Google Scholar and two sources of conference abstracts. Primary clinical studies focused on QST assessment in patients with BMS were included. Data were synthesised qualitatively and quantitatively. Risk of bias was assessed following the AHRQ guidelines. RESULTS Thirteen articles with low to moderate risk of bias and one conference abstract were selected from 45 unique articles that were identified. Individually, the studies reported combinations of thermal and mechanical sensory impairments measured by QST. The meta-analysis showed significant sensory differences between patients and controls in warmth (effect size = 0.683; P < .05) and cold detection thresholds (effect size = -0.580; P < .001). CONCLUSION The results indicate that thermal sensitivity seems to be altered in patients with BMS compared to controls, suggesting a small-fibre neuropathy. However, study protocols were highly variable and heterogeneous. Therefore, studies with better designs and complete reporting of results should be performed to bring value to the use of psychophysics in the assessment of BMS.
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Affiliation(s)
- Víctor I Madariaga
- Division of Oral Diagnostics and Rehabilitation, Department of Dental Medicine, Scandinavian Center for Orofacial Neurosciences (SCON), Karolinska Institutet, Huddinge, Sweden
| | - Hirokazu Tanaka
- Division of Oral Diagnostics and Rehabilitation, Department of Dental Medicine, Scandinavian Center for Orofacial Neurosciences (SCON), Karolinska Institutet, Huddinge, Sweden.,Oral Disease Center, Aizawa Hospital, Matsumoto, Japan.,Department of Dentistry and Oral Surgery, Shinshu University School of Medicine, Matsumoto, Japan
| | - Malin Ernberg
- Division of Oral Diagnostics and Rehabilitation, Department of Dental Medicine, Scandinavian Center for Orofacial Neurosciences (SCON), Karolinska Institutet, Huddinge, Sweden
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16
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Vecchio E, Lombardi R, Paolini M, Libro G, Delussi M, Ricci K, Quitadamo SG, Gentile E, Girolamo F, Iannone F, Lauria G, de Tommaso M. Peripheral and central nervous system correlates in fibromyalgia. Eur J Pain 2020; 24:1537-1547. [PMID: 32478943 DOI: 10.1002/ejp.1607] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/13/2019] [Revised: 05/14/2020] [Accepted: 05/21/2020] [Indexed: 12/11/2022]
Abstract
BACKGROUND Fibromyalgia (FM) is a syndrome characterized by altered pain processing at central and peripheral level, whose pathophysiologic mechanisms remain obscure. We aimed at exploring the structural changes of peripheral nociceptor measured by skin biopsy, the functional changes of central nociceptive pathway assessed by laser-evoked potentials (LEP), and their correlation with clinical features and comorbidities. METHODS In all, 81 patients diagnosed with FM underwent skin biopsies with quantification of intraepidermal nerve fibre density (IENFD) at the thigh and distal leg, and LEP recording by stimulating hand, thigh and foot. Nerve conduction study (NCS), clinical features, comorbidity with migraine and mood disorders, and previous, non-active immune-mediated disorders were recorded. RESULTS Intraepidermal nerve fibre density was reduced in 85% of patients at the thigh and in 12.3% of patients at the distal leg, whereas it was normal in 14.8% of patients. N2P2 habituation index from laser stimulation at the thigh was altered in 97.5% of patients and correlated with reduced IENFD at the thigh. LEP latencies and amplitudes did not differ among groups. No association was found between IENFD, LEP, clinical features and comorbidities. CONCLUSIONS Fibromyalgia patients most commonly showed a mild loss of peripheral nociceptors at the thigh rather than distal small fibre neuropathy. This finding was associated with an altered habituation index and strengthened the hypothesis that central sensitization plays a key role in the pathogenesis of the disease. SIGNIFICANCE Central impairment of pain processing likely underlies FM, which in most patients is associated with mild proximal small fibre pathology.
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Affiliation(s)
- Eleonora Vecchio
- Applied Neurophysiology and Pain Unit, Department of Basic Medical Sciences Neurosciences and Sensory Organs, University of Bari "Aldo Moro", Bari, Italy
| | - Raffaella Lombardi
- 3rd Neurology Unit and Skin Biopsy, Department of Clinical Neurosciences, Peripheral Neuropathy and Neuropathic Pain Laboratory, IRCCS Foundation, 'Carlo Besta' Neurological Institute, Milan, Italy
| | - Matilde Paolini
- 3rd Neurology Unit and Skin Biopsy, Department of Clinical Neurosciences, Peripheral Neuropathy and Neuropathic Pain Laboratory, IRCCS Foundation, 'Carlo Besta' Neurological Institute, Milan, Italy
| | - Giuseppe Libro
- Applied Neurophysiology and Pain Unit, Department of Basic Medical Sciences Neurosciences and Sensory Organs, University of Bari "Aldo Moro", Bari, Italy
| | - Marianna Delussi
- Applied Neurophysiology and Pain Unit, Department of Basic Medical Sciences Neurosciences and Sensory Organs, University of Bari "Aldo Moro", Bari, Italy
| | - Katia Ricci
- Applied Neurophysiology and Pain Unit, Department of Basic Medical Sciences Neurosciences and Sensory Organs, University of Bari "Aldo Moro", Bari, Italy
| | - Silvia G Quitadamo
- Applied Neurophysiology and Pain Unit, Department of Basic Medical Sciences Neurosciences and Sensory Organs, University of Bari "Aldo Moro", Bari, Italy
| | - Eleonora Gentile
- Applied Neurophysiology and Pain Unit, Department of Basic Medical Sciences Neurosciences and Sensory Organs, University of Bari "Aldo Moro", Bari, Italy
| | - Francesco Girolamo
- Unit of Human Anatomy and Histology, Department of Basic Medical Sciences, Neurosciences and Sensory Organs, School of Medicine, University of Bari, Bari, Italy
| | - Florenzo Iannone
- Rheumatology Unit, Department of Emergency and Organ Transplantation, University of Bari, Bari, Italy
| | - Giuseppe Lauria
- 3rd Neurology Unit and Skin Biopsy, Department of Clinical Neurosciences, Peripheral Neuropathy and Neuropathic Pain Laboratory, IRCCS Foundation, 'Carlo Besta' Neurological Institute, Milan, Italy.,Department of Biomedical and Clinical Sciences "Luigi Sacco", University of Milan, Milan, Italy
| | - Marina de Tommaso
- Applied Neurophysiology and Pain Unit, Department of Basic Medical Sciences Neurosciences and Sensory Organs, University of Bari "Aldo Moro", Bari, Italy
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17
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Affiliation(s)
- C.C. Currie
- School of Dental Sciences Newcastle University Framlington Place Newcastle Upon Tyne NE2 4BW UK
| | - S.K. Jääskeläinen
- Department of Clinical Neurophysiology Turku University Hospital and University of Turku Turku Finland
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