Journal
FRONTIERS IN PHARMACOLOGY
Volume 11, Issue -, Pages -Publisher
FRONTIERS MEDIA SA
DOI: 10.3389/fphar.2020.614450
Keywords
cynandione A; neuropathic pain; interleukin-10; β -endorphin; α 7 nicotinic acetylcholine receptor; microglia
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The study found that cynandione A suppresses neuropathic pain through an alpha 7-nAChR-dependent IL-10/beta-endorphin signaling pathway in spinal microglia.
Cynandione A, an acetophenone isolated from Cynanchum Wilfordii Radix, exhibits antineuropathic pain effect. This study further explored the target molecule and signaling mechanisms underlying cynandione-A-induced antineuropathic pain. Intrathecal injection of cynandione A significantly attenuated mechanical allodynia in neuropathic rats and substantially increased spinal expression of IL-10 and beta-endorphin but not dynorphin A. Cynandione A treatment also enhanced expression of IL-10 and beta-endorphin but not alpha 7 nicotinic acetylcholine receptors (nAChRs) in cultured microglia. The IL-10 antibody attenuated cynandione-A-induced spinal or microglial gene expression of beta-endorphin and mechanical allodynia, whereas the beta-endorphin antiserum blocked cynandione-A-induced mechanical antiallodynia but not spinal or microglial IL-10 gene expression. The alpha 7 nAChR antagonist methyllycaconitine significantly reduced cynandione-A-induced mechanical antiallodynia and spinal or microglial expression of IL-10 and beta-endorphin. Furthermore, cynandione A stimulated microglial phosphorylation of PKA, p38, and CREB in an alpha 7-nAChR-dependent manner, and treatment with their inhibitors attenuated cynandione-A-induced mechanical antiallodynia and spinal or microglial expression of IL-10 and beta-endorphin. In addition, cynandione A stimulated spinal phosphorylation of the transcription factor STAT3, which was inhibited by methyllycaconitine, the PKA activation inhibitor or IL-10 antibody. The STAT3 inhibitor NSC74859 also abolished cynandione-A-induced mechanical antiallodynia and spinal expression of beta-endorphin. These findings suggest that cynandione A suppresses neuropathic pain through alpha 7-nAChR-dependent IL-10/beta-endorphin signaling pathway in spinal microglia.
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