Review
Copyright ©The Author(s) 2015. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Diabetes. Apr 15, 2015; 6(3): 432-444
Published online Apr 15, 2015. doi: 10.4239/wjd.v6.i3.432
Diabetic neuropathic pain: Physiopathology and treatment
Anne K Schreiber, Carina FM Nones, Renata C Reis, Juliana G Chichorro, Joice M Cunha
Anne K Schreiber, Carina FM Nones, Renata C Reis, Juliana G Chichorro, Joice M Cunha, Department of Pharmacology, Biological Sciences Sector, Federal University of Parana, Curitiba 81540-970, Brazil
Author contributions: All authors contributed equally to this work.
Conflict-of-interest: None.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Dr. Joice M Cunha, Professor, Department of Pharmacology, Biological Sciences Sector, Federal University of Parana, Rua XV de Novembro, 1299 - Centro, Curitiba 81540-970, Brazil. joice.cunha@ufpr.br
Telephone: +55-41-33611720 Fax: +55-41-32662042
Received: August 29, 2014
Peer-review started: August 30, 2014
First decision: November 14, 2014
Revised: November 26, 2014
Accepted: February 4, 2015
Article in press: February 9, 2015
Published online: April 15, 2015
Processing time: 234 Days and 8.2 Hours
Abstract

Diabetic neuropathy is a common complication of both type 1 and type 2 diabetes, which affects over 90% of the diabetic patients. Although pain is one of the main symptoms of diabetic neuropathy, its pathophysiological mechanisms are not yet fully known. It is widely accepted that the toxic effects of hyperglycemia play an important role in the development of this complication, but several other hypotheses have been postulated. The management of diabetic neuropathic pain consists basically in excluding other causes of painful peripheral neuropathy, improving glycemic control as a prophylactic therapy and using medications to alleviate pain. First line drugs for pain relief include anticonvulsants, such as pregabalin and gabapentin and antidepressants, especially those that act to inhibit the reuptake of serotonin and noradrenaline. In addition, there is experimental and clinical evidence that opioids can be helpful in pain control, mainly if associated with first line drugs. Other agents, including for topical application, such as capsaicin cream and lidocaine patches, have also been proposed to be useful as adjuvants in the control of diabetic neuropathic pain, but the clinical evidence is insufficient to support their use. In conclusion, a better understanding of the mechanisms underlying diabetic neuropathic pain will contribute to the search of new therapies, but also to the improvement of the guidelines to optimize pain control with the drugs currently available.

Keywords: Diabetes; Neuropathic pain; Hyperglycemia; Anticonvulsants; Antidepressants

Core tip: Diabetic neuropathic pain is a common complication of diabetes and the most common form of neuropathic pain. In this review, we will discuss the various factors that may contribute to the pathogenesis of diabetic neuropathic pain, including metabolic, vascular, autoimmune and oxidative stress-related mechanisms. In addition, we will review the possibilities of pain treatment, taken into consideration the first line drugs clinically used, the antidepressants and anticonvulsants, but also other options such as opioids, tapentadol and drugs for topical use, such as lidocaine and capsaicin cream.