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

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 vin...

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Bibliographic Details
Published in:PloS one 2014-02, Vol.9 (2), p.e89583
Main Authors: Yang, Yang, Zhang, Yong-Gang, Lin, Guo-An, Xie, He-Qiu, Pan, Hai-Tao, Huang, Ben-Qing, Liu, Ji-Dong, Liu, Hui, Zhang, Nan, Li, Li, Chen, Jian-Hua
Format: Article
Language:English
Subjects:
Analgesia
Analgesics
Analysis
Animals
Antineoplastic Agents, Phytogenic - toxicity
Biology
Cancer
Chemotherapy
Dipeptidyl-peptidase IV
Dipeptidyl-Peptidases and Tripeptidyl-Peptidases - metabolism
Drug dosages
Electrophysiology
Endogenous opioids
Endomorphin-2
Fluorescent Antibody Technique
Hyperalgesia - chemically induced
Hyperalgesia - metabolism
Hyperalgesia - pathology
Immunoblotting
Immunoenzyme Techniques
Injections, Spinal
Ligands
Male
Medicine
Metabolism
Narcotics
Neuralgia
Neuralgia - chemically induced
Neuralgia - metabolism
Neuralgia - pathology
Neuropathy
Neurosciences
Neurosurgery
Oligopeptides - metabolism
Opioid receptors (type mu)
Oxidative stress
Pain
Pain perception
Peptides
Rats
Rats, Sprague-Dawley
Reactive Oxygen Species - metabolism
Rodents
Spinal cord
Spinal Cord - drug effects
Spinal Cord - metabolism
Studies
Vincristine
Vincristine - toxicity
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Summary: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.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0089583