Metformin relieves neuropathic pain after spinal nerve ligation via autophagy flux stimulation.

Abstract

Neuropathic pain is a well-known type of chronic pain caused by damage to the nervous system. Autophagy is involved in the development and/or progression of many diseases, including neuropathic pain. Emerging evidence suggests that metformin relieves neuropathic pain in several neuropathic pain models; however, metformin's cellular and molecular mechanism for pain relief remains unknown. In this study, we investigated the therapeutic effects of metformin on pain relief after spinal nerve ligation (SNL) and its underlying mechanism of autophagy regulation. Behavioural analysis, histological assessment, expression of c-Fos and molecular biological changes, as well as ultrastructural features, were investigated. Our findings showed that the number of autophagosomes and expression of autophagy markers, such as LC3 and beclin1, were increased, while the autophagy substrate protein p62, as well as the ubiquitinated proteins, were accumulated in the ipsilateral spinal cord. However, metformin enhanced the expression of autophagy markers, while it abrogated the abundance of p62 and ubiquitinated proteins. Blockage of autophagy flux by chloroquine partially abolished the apoptosis inhibition and analgesic effects of metformin on SNL. Taken together, these results illustrated that metformin relieved neuropathic pain through autophagy flux stimulation and provided a new direction for metformin drug development to treat neuropathic pain.

• Authors: Weidong Weng, Chenglun Yao, Keshav Poonit, Xijie Zhou, Chao Sun, Feng Zhang, Hede Yan
• Journal: Journal of cellular and molecular medicine (J Cell Mol Med) Vol. 23 Issue 2 Pg. 1313-1324 (02 2019) ISSN: 1582-4934 [Electronic] England
• PMID: 30451370 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2018 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

Chemical References

• Hypoglycemic Agents
• Metformin

Topics

• Animals
• Autophagosomes
• Autophagy
• Behavior, Animal (drug effects)
• Hypoglycemic Agents (pharmacology)
• Ligation
• Male
• Metformin (pharmacology)
• Neuralgia (drug therapy, etiology, pathology)
• Rats
• Rats, Sprague-Dawley
• Spinal Nerves (pathology, surgery)
• Surgical Procedures, Operative (adverse effects)