Open AccessSpinal Changes of a Newly Isolated Neuropeptide Endomorphin-2 Concomitant with Vincristine-Induced Allodynia
Author(s) -
Yang Yang,
Yonggang Zhang,
Guo-An Lin,
He-Qiu Xie,
Haitao Pan,
Ben-Qing Huang,
Jidong Liu,
Hui Liu,
Nan Zhang,
Li Li,
Jianhua Chen
Publication year - 2014
Publication title -
plos one
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.99
H-Index - 332
ISSN - 1932-6203
DOI - 10.1371/journal.pone.0089583
Subject(s) - allodynia , neuropathic pain , medicine , pharmacology , vincristine , antagonist , sensitization , hyperalgesia , neuropeptide , anesthesia , receptor antagonist , chemotherapy , nociception , receptor , immunology , cyclophosphamide
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.