Tropisetron attenuates neuroinflammation and chronic neuropathic pain via α7nAChR activation in the spinal cord in rats

AbstractObjectives Tropisetron is an alpha 7 nicotinic acetylcholine receptor (α7nAChR) agonist and is a commonly used antiemetic clinically. α7nAChRs activation modulating nociception transmissions and cholinergic anti-inflammation may decrease neuropathic pain. This study was set to investigate the effects of tropisetron on neuropathic pain and neuroinflammation as well as the underlying mechanisms in rats.Methods Neuropathic pain behavior was assessed in rats using the paw mechanical withdrawal threshold and paw thermal withdrawal latency before and after the establishment of a spared nerve injury (SNI) pain model in rats treated with tropisetron treatment in the presence or absence of the α7nAChR antagonist methyllycaconitine (MLA) through intrathecal injection. Their spinal cords were then harvested for inflammatory cytokines, the α7nAChR, p38 mitogen-activated protein kinase (p-p38MAPK) and cAMP-response element binding protein (CREB) measurement.Results Tropisetron effectively alleviated mechanical allodynia and thermal hyperalgesia; decreased IL-6, IL-1ß and TNF-a; and down-regulated the phosphorylation of p38MAPK and CREB. Pre-treatment with MLA abolished these effects of tropisetron.Conclusion Our data indicate that tropisetron alleviates neuropathic pain may through inhibition of the p38MAPK-CREB pathway via α7nAChR activation. Thus, tropisetron may be a potential new therapeutic strategy for chronic neuropathic pain.Keywords: Tropisetronα7nAChRChronic neuropathic painPain sensitizationNeuroinflammation AcknowledgementsAuthors thank to Prof Daqing Ma, Imperial College London, for his critical comments during manuscript preparation.Conflict of interestNo potential conflict of interest was reported by the author(s).Funding This work was supported by the National key Research and Development Program of China (2018YFC2001904), the National Natural Science Foundation for Youth of China (81700082), and the Natural science Foundation of Hubei Province of China (2020CFB335).Correction StatementThis article has been republished with minor changes. These changes do not impact the academic content of the article.Additional informationFundingThis work was supported by the National key Research and Development Program (2018YFC2001900), the National Natural Science Foundation for Youth of China (81700082), and the Natural science Foundation of Hubei Province of China (2020CFB335).