An Experiment Study Of GTP Cyclohydrolase â…  Expression And Neuronal Apoptosis In Rat Spinal Dorsal Cord Induced By Sciatic Nerve Chronic Constrictive Injury

Background:The pathogenesis of paresthesia and hyperpathia induced by peripheral nerve injury is quite complicated. GTP cyclohydrolase1(GCH1) is the synthase and rate-limiting enzyme of tetrahydrobiopterin (BH4), which plays some roles in neuropathic pain and Inflammatory pain, but there are few reports about it at spinal cord levels.Objective:In this research, we established the chronic constrictive injury model, and abserved the expression of GCH1and nerve cell apoptosis in rats spinal dorsal cord to investigate their relationship with neuropathic pain.Methods:80Wistar rats were divided randomly into2groups, CCI group (n=40) and sham group (n=40). The mechanical withdrawal threshold (MWT) was measured by von Frey filaments on1day before operation and the3th,7th,14th,28th days after operation. The L4-L6segments of spinal cord were also executed respectivelyt,5rats in every time piont of each group were used in immunohistochemical and TUNEL, other3ones were used in Western Blotting. The expression of GCH1and neuronal apoptosis in spinal dorsal cord were measured and counted finally.Results:1. Mechanical withdrawal threshold test:Compared with the sham group, MWT in the CCI group was obviously decreased after operation (P<0.05), it kept a low level from the3th day and the14th day after the injury, then the threshold rised slightly, but still cant rearch the normal level (P<0.05).2. GCH1expression:The immunohistochemistry detection showed that, after chronic constriction injury, the expression of GCH1in spinal dorsal horn it increased significantly compared with pre-operation and sham group (P<0.05), it rose first and then fell. The variation tendency of GCH1in western blotting is according with the immunohistochemistry detection, GCH1expression in the CCI group increased on the3rd,7th,14th days compared with the sham group (P<0.05), and on the28th day postoperatively, there was no statistical difference (P>0,05).3. Neuronal apoptosis:After sciatic nerve chronic compression injury, apoptotic cells in spinal dorsal cord of L4-6increased gradually, it reached the top on day14after surgery, the apoptosis index on every time piont postoperative in CCI group were all above the sham operation rats level (P<0.05).Conclusion:Sciatic nerve chronic compression injury induced rats spontanous pain behaviors, such as autophagy and self-protective, and their mechanical withdrawal threshold declined obviously. The expression of GCH1and neuronal apoptosis in spinal dorsal cord of L4-6increaced significantly, so we speculated that they might participate in the generation of neuropathic pain.