Inhibition of apoptosis signal-regulating kinase by paeoniflorin attenuates neuroinflammation and ameliorates neuropathic pain

Autor: Danli Zhou, Siqi Zhang, Liang Hu, Yu-Feng Gu, Yimei Cai, Deqin Wu, Wen-Tao Liu, Chun-Yi Jiang, Xiangqing Kong, Guang-Qin Zhang
Jazyk: angličtina
Rok vydání: 2019
Předmět:
Zdroj: Journal of Neuroinflammation, Vol 16, Iss 1, Pp 1-11 (2019)
Druh dokumentu: article
ISSN: 1742-2094
DOI: 10.1186/s12974-019-1476-6
Popis: Abstract Background Neuropathic pain is a serious clinical problem that needs to be solved urgently. ASK1 is an upstream protein of p38 and JNK which plays important roles in neuroinflammation during the induction and maintenance of chronic pain. Therefore, inhibition of ASK1 may be a novel therapeutic approach for neuropathic pain. Here, we aim to investigate the effects of paeoniflorin on ASK1 and neuropathic pain. Methods The mechanical and thermal thresholds of rats were measured using the Von Frey test. Cell signaling was assayed using western blotting and immunohistochemistry. Results Chronic constrictive injury (CCI) surgery successfully decreased the mechanical and thermal thresholds of rats and decreased the phosphorylation of ASK1 in the rat spinal cord. ASK1 inhibitor NQDI1 attenuated neuropathic pain and decreased the expression of p-p38 and p-JNK. Paeoniflorin mimicked ASK1 inhibitor NQDI1 and inhibited ASK1 phosphorylation. Paeoniflorin decreased the expression of p-p38 and p-JNK, delayed the progress of neuropathic pain, and attenuated neuropathic pain. Paeoniflorin reduced the response of astrocytes and microglia to injury, decreased the expression of IL-1β and TNF-α, and downregulated the expression of CGRP induced by CCI. Conclusions Paeoniflorin is an effective drug for the treatment of neuropathic pain in rats via inhibiting the phosphorylation of ASK1, suggesting it may be effective in patients with neuropathic pain.
Databáze: Directory of Open Access Journals
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