Preemptive intrathecal administration of endomorphins relieves inflammatory pain in male mice via inhibition of p38 MAPK signaling and regulation of inflammatory cytokines

Autor: Ting Zhang, Nan Zhang, Run Zhang, Weidong Zhao, Yong Chen, Zilong Wang, Biao Xu, Mengna Zhang, Xuerui Shi, Qinqin Zhang, Yuanyuan Guo, Jian Xiao, Dan Chen, Quan Fang
Jazyk: angličtina
Rok vydání: 2018
Předmět:
Zdroj: Journal of Neuroinflammation, Vol 15, Iss 1, Pp 1-14 (2018)
Druh dokumentu: article
ISSN: 1742-2094
DOI: 10.1186/s12974-018-1358-3
Popis: Abstract Background Preemptive administration of analgesic drugs reduces perceived pain and prolongs duration of antinociceptive action. Whereas several lines of evidence suggest that endomorphins, the endogenous mu-opioid agonists, attenuate acute and chronic pain at the spinal level, their preemptive analgesic effects remain to be determined. In this study, we evaluated the anti-allodynic activities of endomorphins and explored their mechanisms of action after preemptive administration in a mouse model of inflammatory pain. Methods The anti-allodynic activities of preemptive intrathecal administration of endomorphin-1 and endomorphin-2 were investigated in complete Freund’s adjuvant (CFA)-induced inflammatory pain model and paw incision-induced postoperative pain model. The modulating effects of endomorphins on the expression of p38 mitogen-activated protein kinase (p38 MAPK) and inflammatory mediators in dorsal root ganglion (DRG) of CFA-treated mice were assayed by real-time reverse transcription-polymerase chain reaction (RT-PCR), Western blotting, or immunofluorescence staining. Results Preemptive intrathecal injection of endomorphins dose-dependently attenuated CFA-induced mechanical allodynia via the mu-opioid receptor and significantly reversed paw incision-induced allodynia. In addition, CFA-caused increase of phosphorylated p38 MAPK in DRG was dramatically reduced by preemptive administration of endomorphins. Repeated intrathecal application of the specific p38 MAPK inhibitor SB203580 reduced CFA-induced mechanical allodynia as well. Further RT-PCR assay showed that endomorphins regulated the mRNA expression of inflammatory cytokines in DRGs induced by peripheral inflammation. Conclusions Our findings reveal a novel mechanism by which preemptive treatment of endomorphins attenuates inflammatory pain through regulating the production of inflammatory cytokines in DRG neurons via inhibition of p38 MAPK phosphorylation.
Databáze: Directory of Open Access Journals
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