Abstract
BackgroundNeuropathic 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.MethodsThe mechanical and thermal thresholds of rats were measured using the Von Frey test. Cell signaling was assayed using western blotting and immunohistochemistry.ResultsChronic 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.ConclusionsPaeoniflorin 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.
Highlights
IntroductionASK1 is an upstream protein of p38 and Jun N-terminal kinase (JNK) which plays important roles in neuroinflammation during the induction and maintenance of chronic pain
Neuropathic pain is a serious clinical problem that needs to be solved urgently
Convincing evidences show that the mitogen-activated protein kinase (MAPK) families are important for the central sensitization, especially chronic pain caused by glial cell-induced neuroinflammation during the induction and maintenance of chronic pain [9, 10]
Summary
ASK1 is an upstream protein of p38 and JNK which plays important roles in neuroinflammation during the induction and maintenance of chronic pain. There are many ion channels and receptors on the cell membrane, involving in central sensitization [6, 8]. It is important to find new analgesic targets, especially key molecules responsible for central sensitization. Convincing evidences show that the mitogen-activated protein kinase (MAPK) families are important for the central sensitization, especially chronic pain caused by glial cell-induced neuroinflammation during the induction and maintenance of chronic pain [9, 10]. Choosing the appropriate target molecule to inhibit the activation of JNK and p38 becomes a very appealing analgesic strategy
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