The Analgesic Effect And Mechanism Of The Oxysophocarpine In Mice

Objectives To observe the analgesic effect of OSC (oxysophocarpine, OSC) and studywhether or not it relate to the metabolism of GABA and GABA-A in cerebral cortex andhypothalamus.Method1. Behavioral pharmacology:①Treating warm water tail-flick test’s thresholdof pain as the index to observe analgesic strength and analyze the mainly analgesic site ofOSR by vein injection (i.v.) and intracerebroventricularly injection (i.c.v.),②AdoptingGABA（gamma aminobutyric acid，GABA）, GABA synthetase inhibitor, GABA receptoragonists and GABA receptor antagonists to investigate the analgesic effects influence andanalyze the analgesic mechanisms of OSC.2. Immunohistochemistry method (SABC) to determine the GABAARα1, which lie incerebral cortex and hippocampi in mice, and analyse the analgesic mechanism of OSCwhether involved GABAAreceptor.3. Western blot to test the influence of OSC on protein content caused by warm watertail-flick test in GABAARα1of brain of mice, and analyze influence of GABAARα1of brainon analgesic effect.Results1. Compared with NS group，i.c.v. OSC(1、4mg/kg) significantly prolongedthe tail-curling latencies of mice at15min,30min,60min,90min in the warm water tail-flicktest (P<0.01), it’s analgesic effect could last about90min. The strongest analgesic effect was34.66%. Compared with NS group, ith OSC (1,4mg/kg) significantly prolonged the tail-curling latencies of mice at15min,30min,60min,90min in the warm water tail-flick test(P<0.01), it’s analgesic effect could last about90min. The strongest analgesic effect was29.91%. It suggested that the analgesia mechanism of OSC probabaly involved centralnervous system (CNS).2. Compared with OSC (6mg/kg), i.c.v. Gamma-aminobutyric acid1.6mg/kg and0.1×10－3mg Muscimol, which was GABAAspecific receptor inhibitor significantly enhancedthe analgesic effects of OSC (6mg/kg)(P<0.01). Compared with OSC (80mg/kg), i.c.v.0.2×10－3mg Bicuculine, which was GABAAspecific receptor inhibitorand0.1×10－3mgPicrotoxin, GABAAnon-specific receptor inhibitor were also significantly inhanced theanalgesic effects of OSC (80mg/kg)(P<0.01). It suggested that the analgesia mechanism ofOSC probabaly related to GABAAreceptor.3. Compared with NS group, OSC could increase the number of GABAARα1, whichlied in cerebral cortex and hippocampi of mice (P<0.01). OSC could also increase the averageoptical density and gray level in posterior horn of spinal cord (P<0.01).4. Compared with NS group, OSC (80mg/kg, i.p.) inhibited the expression of GABAARα1’sprotein which was caused by warm water tail-flick test. It suggested that the GABAARα1probably involve in the analgesic action of OSC.Conclusions The result indicated that OSC has obvious analgesic effects and itsmechanism may be involved in central nervous system (CNS) and peripheral nervous system(PNS). The analgesic sites of OSC were mainly related cerebral cortex and hippocampi. Themechanism of OSC was probably that it stimulated the expression of GABAAReceptor.