Abstract:Objective: To explore whether intrathecal injection of tropisetron alleviates chronic neuropathic pain and p38 mitogen-activated protein kinase (p38MAPK) expression in rats with spared nerve injury (SNI) by activating alpha 7 nicotinic acetylcholine receptor (α7nAChR) . Methods: Adult male SD rats weighing 180-220 g were randomly divided into 5 groups (n=12/each group): sham operation group, nerve injury group, tropisetron group, α7nAChR antagonist methyllycaconitine citrate group (MLA group), and MLA+tropisetron group. The right sciatic nerve was exposed only in the sham operation group, and the right sciatic nerve injury models were made in the nerve injury group, tropisetron group, MLA group and MLA+tropisetron group. On the 14th day after the establishment of the pain model, the drugs were administered intrathecally, and the pain behavior was observed and tested at different time. One hour after administration, the rats were sacrificed and the L4-6 segments of spinal cord were removed. The distribution and expression of α 7nAChR in spinal dorsal horn were observed by tissue immunofluorescence staining. Western blot was used to detect the changes of α7nAChR, p-p38 and p38 protein expression. Results: The paw mechanical withdrawal threshold (PMWT) and paw thermal withdrawal latency (PTWL) in tropisetron group and MLA+tropisetron group were significantly higher than those before administration, and that in MLA+tropisetron group was lower than that in tropisetron group. There was no significant change in PMWT and PTWL in MLA group before and after administration. The immunofluorescence results of α7nAChR showed that the positive area in the nerve injury group was significantly lower than that in the sham operation group. The positive staining in tropisetron group and MLA+tropisetron group was significantly higher than that in nerve injury group. Western blot results showed that the expression of α 7nAChR in tropisetron group and MLA+tropisetron group was significantly higher than that in nerve injury group, while the expression level of p-p38 protein in tropisetron group was significantly lower than that in nerve injury group. There was no significant difference in the expression level of p38 protein among all groups. Conclusion: Intrathecal injection of tropisetron can relieve chronic neuropathic pain in SNI rats, and α7nAChR antagonist MLA can block its pain-relieving effect to some extent. The mechanism may be related to the selective activation of α7nAChR and inhibition of p38MAPK signal pathway by tropisetron.
