Spinal changes of a newly isolated neuropeptide endomorphin-2 concomitant with vincristine-induced allodynia.

Abstract

Chemotherapy-induced neuropathic pain (CNP) is the major dose-limiting factor in cancer chemotherapy. However, the neural mechanisms underlying CNP remain unclear. There is increasing evidence implicating the involvement of spinal endomorphin-2 (EM2) in neuropathic pain. In this study, we used a vincristine-evoked rat CNP model displaying mechanical allodynia and central sensitization, and observed a significant decrease in the expression of spinal EM2 in CNP. Also, while intrathecal administration of exogenous EM2 attenuated allodynia and central sensitization, the mu-opioid receptor antagonist β-funaltrexamine facilitated these events. We found that the reduction in spinal EM2 was mediated by increased activity of dipeptidylpeptidase IV, possibly as a consequence of chemotherapy-induced oxidative stress. Taken together, our findings suggest that a decrease in spinal EM2 expression causes the loss of endogenous analgesia and leads to enhanced pain sensation in CNP.

• Authors: Yang Yang, Yong-Gang Zhang, Guo-An Lin, He-Qiu Xie, Hai-Tao Pan, Ben-Qing Huang, Ji-Dong Liu, Hui Liu, Nan Zhang, Li Li, Jian-Hua Chen
• Journal: PloS one (PLoS One) Vol. 9 Issue 2 Pg. e89583 ( 2014) ISSN: 1932-6203 [Electronic] United States
• PMID: 24586889 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents, Phytogenic
• Oligopeptides
• Reactive Oxygen Species
• endomorphin 2
• Vincristine
• Dipeptidyl-Peptidases and Tripeptidyl-Peptidases

Topics

• Animals
• Antineoplastic Agents, Phytogenic (toxicity)
• Dipeptidyl-Peptidases and Tripeptidyl-Peptidases (metabolism)
• Electrophysiology
• Fluorescent Antibody Technique
• Hyperalgesia (chemically induced, metabolism, pathology)
• Immunoblotting
• Immunoenzyme Techniques
• Injections, Spinal
• Male
• Neuralgia (chemically induced, metabolism, pathology)
• Oligopeptides (metabolism)
• Rats
• Rats, Sprague-Dawley
• Reactive Oxygen Species (metabolism)
• Spinal Cord (drug effects, metabolism)
• Vincristine (toxicity)