Gelsemine attenuates neuropathic pain in a rat model of sciatic nerve chronic constriction injury.

ObjectiveThe effect of Gelsemine on neuropathic pain was investigated using a sciatic nerve (SN) chronic constriction injury (CCI) rat model.MethodsNetwork pharmacology analysis was performed to identify potential molecular targets of Gelsemine associated with neuropathic pain, followed by molecular docking analysis of the identified targets. Neuropathic pain was induced in male rats by SN-CCI. The rats were divided into four groups: sham, CCI, Gelsemine 2 mg/kg, and Gelsemine 4 mg/kg. Gelsemine (2 or 4 mg/kg, i.p.) was administered to the treatment groups for 30 consecutive days. The effect of Gelsemine on mechanical hypersensitivity was evaluated, and the BBB score was used as a secondary assessment of general locomotor function following CCI. The levels and expression of inflammatory mediators were analyzed by ELISA and qRT-PCR, respectively, and the expression of THIK1, caspase-8, and cytosolic phospholipase A2 (cPLA2) in nerve tissue was analyzed by western blot.ResultsNetwork pharmacology analysis identified ASK1 and TrkB (NTRK2) as potential molecular targets of Gelsemine in neuropathic pain, and molecular docking predicted favorable binding interactions with these proteins. Gelsemine significantly attenuated mechanical hypersensitivity and improved BBB locomotor scores in CCI rats. It also reduced the altered serum levels of IL-4, IL-6, IL-1β, and TNF-α, as well as the mRNA expression of NF-κB, IL-6, and TNF-α, compared with the CCI group. Furthermore, Gelsemine was associated with significantly reduced mRNA expression of ASK1, TrkB (NTRK2), and MAPK1 in SN tissue and normalization of the altered expression of THIK1, caspase-8, and cPLA2 in male CCI rats.ConclusionGelsemine alleviated mechanical hypersensitivity and improved locomotor function, while ameliorating inflammatory and oxidative stress-related changes in male CCI rats. Computational analyses identified ASK1 and TrkB (NTRK2) as potential molecular targets, while Gelsemine treatment was associated with reduced expression of ASK1, TrkB, and MAPK1. These findings suggest a possible association between Gelsemine treatment and ASK1/TrkB/MAPK-related signaling; however, further functional studies are required to establish their causal involvement in the analgesic effects of Gelsemine. Only male rats were included in this study; therefore, the findings are limited to male physiology and cannot be generalized to female animals.