Analgesic Effects And Mechanisms Of L-Tetrahydropalmatine In The Rats’ Model Of Chronic Constriction Injury Neuropathic Pain

Objective:To evaluate the effects of Levo-tetrahydropalmatine (L-THP, a traditional chinese medicine) in neuropathic pain of the rats’model of sciatic nerve chronic constriction injury. Moreover, to observe the effects of combined L-THP with URB597、URB602(specific irreversible inhibitors for fatty acid amide hydrolase FAAH and, monoacylglycerol lipase MAGL) respectively in neuropathic pain CCI rats’model.Methods:Total84Wistar male rats were divided at random into five groups, as follows: Sham(S group)、CCI(C group)、L-THP (L group)、L-THP combined with URB597(L1group) and L-THP combined with URB602(L2group). In groups of S、C and L, set post-operation3d、7d and14d three time-point. n=6. Rats’model of neuropathic pain established by inducing chronic constriction injury of sciatic nerve of right hind leg. In group S, sciatic nerves were exposed but not ligated yet, in other four groups, sciatic nerve of right hind legs were exposed and ligated by4-0silk thread. L-THP40mg/kg were performed intraperitoneally in groups L、L1and L2immediately after operation and then once a day for14days continuously; rats in groups S and C were injected isometric normal saline i·p; groups L1and L2were administrated URB597、URB6020.3mg/kg in the local incision of right hind legs from11th day of post-operation once a day for4days; Isometric normal saline was administrated for rats in groups S、C and L. Rats’mechanical allodynia (MWT) and thermal hyperalgesia (TWL) were tested by VonFrey filaments and infrared noxious heat stimulator in all five groups on1d pre-operation.6rats in S、C and L each group were executed to performe Western blot to observe the changes of fatty acid amide hydrolase (FAAH) in the rats’hippocampus after mechanical allodynia and thermal hyperalgesia were tested on post-operation3d、7d and14d three time-point. In other groups mechanical allodynia and thermal hyperalgesia were tested on post-operation3d、7d、11d、12d、13d and14d.Results:Compared with pre-operation and group S, thresholds of MWT and TWL were decreased on post-operation3d、7d and14d in groups C、L、L1and L2(P<0.05); Compared with group C, thresholds of MWT and TWL were increased obviously in groups L、L1and L2on days3d、7d、11d、12d、13d and14d of post-operation (P<0.05);Compared with group L, thresholds were increased in groups L1and L2on days of11d、12d、13d and14d post-operation (P<0.05);There were no differences of thresholds MWT and TWL were found between groups L1and L2(P>0.05).Expression of FAAH was degraded in rats’hippocampus of group L compare with group S and C in the post-operation3d、7d and14d three time-point (P<0.05).Conclusion:In CCI rats’model, L-THP produced a favourable analgestic effects and, FAAH may involves in this effect, enhanced effects were observed when combined L-THP with URB597、URB602respectively, suggesting that L-THP may bacome a promising target for the treatments of neuropathic pain.This may provides a new approch for exploring mechanisms and treatments of neuropathic pain.