Tropisetron attenuates neuroinflammation and chronic neuropathic pain via 7nAChR activation in the spinal cord in rats

Objectives: Tropisetron is an alpha 7 nicotinic acetylcholine receptor (alpha 7nAChR) agonist and is a commonly used antiemetic clinically. alpha 7nAChRs 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 alpha 7nAChR antagonist methyllycaconitine (MLA) through intrathecal injection. Their spinal cords were then harvested for inflammatory cytokines, the alpha 7nAChR, 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-1 beta and TNF-alpha; 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 alpha 7nAChR activation. Thus, tropisetron may be a potential new therapeutic strategy for chronic neuropathic pain.