The Study On Analgesic Effect Of Oxymatrine And Its Mechanism Involved In GABA

Objective To further study the analgesic effects of oxymatrine(OMT) and explore whether the analgesic mechanism of OMT is related to GABA nerve system in posterior horn of spinal cord, cerebral cortex and hypothalamus.Methods It was to adopt different administration routes such as intraperitoneal injection (ip) intrathecal injection (ith) and intracerebroventricularly injection (icv) to observe the analgesic effect of OMT and analyze the mainly analgesic site of OMT in mice . And it was to use mouse S-shaped vertical tail test and naloxone addiction test in mice to observe whether OMT have addiction, and adopt gamma aminobutyric acid(GABA) to investigate the analgesic effects of OMT and analyze its analgesic mechanisms. At last, it was to adopt immunohistochemistry method (SP) and Western blot to determine the GABA ARα1 in posterior horn of spinal cord, cerebral cortex and hippocampus in mice, and analyze the GABAA receptor involved in analgesic mechanism of OMT.Results 1. OMT(180,90 and 45mg/kg, ip) significantly prolonged the tail-curling latencies in the warm water tail-flick test(P<0.01), it's analgesic effect could last more than 90 min; OMT (180,90 and 45mg/kg, imp) remarkably inhibited the two-phase pain in the formalin test(P<0.05,0.01); OMT(180,90 and 45mg/kg, ip) remarkably inhibited and the writhing response in the writhing test on mice(P<0.05,0.01). The strongest analgesic effect was 98.67%. It suggested that the OMT had analgesic effect2. OMT(180,90 and 45mg/kg, ip) don't significantly prolonged response to the vertical tail and jumping reaction. It suggested that OMT don't have addiction 3. OMT (4,2,1mg/kg, icv) significantly prolonged the tail- curling latencies of mice at 15min,30min,45min,60min in the warm water tail-flick test(P<0.01), it's analgesic effect could last about 90min. The strongest analgesic effect was 85.64%. It suggested that the analgesia mechanism of OMT probably involved central nervous system (CNS).4. GABA(2mg/kg, icv) and BIC(4×10^-3mg/kg, icv), which was GABAA specific receptor inhibitor, significantly enhanced the analgesic effects of OMT(25mg/kg)(P<0.01). L-AG(2.5mg/kg, icv), a GABA synthetase inhibitor, and PTX(8×10^-3mg/kg), a GABAA non-specific receptor inhibitor, also significantly inhanced the analgesic effects of OMT(25mg/ kg)(P<0.01), suggesting that the analgesia mechanism of OMT probably related to GABAA receptor.5. OMT could increase the number of GABAARα1, which lied in posterior horn of spinal cord, cerebral cortex and hippocampi of mice(P<0.01). OMT could also increase the average optical density and gray level in posterior horn of spinal cord (P<0.01). OMT ( 180mg/kg, ip) inhibited the downreguation of GABA ARα1 expression caused by formalin, suggesting that the GABA ARα1 probably involve in the analgesic action of OMT.Conclusions The results indicated that OMT has obvious analgesic effects, but no addiction and drug resistance. The underling mechanism may be related with involvement of central nervous system (CNS) and peripheral nervous system (PNS). The analgesic sites of OMT mainly situate in posterior horn of spinal cord, cerebral cortex and hippocampi.In addition, the analgesic mechanism of OMT probably attributed to the increased expression of GABAA Receptor.