Study On The Analgesic Effect And Mechanism Of Intrathecal Administration Sinomenine On Neuropathic Pain Rats

Objective:On this study,we use the spinal nerve ligation model to simulate the neuropathic pain to observe the change of mechanical withdraw threshold and thermal withdraw legacy and compare the analgesic effect by intrathecal administration of sinomenine.We also explore the analgesic mechanism of sinomenine by molecular biochemical methods.Methods:A 8cm PE-10 catheter was placed in the lumbosacral dilatation of rats by intrathecal catheterization in the posterior occiput of the rat.The rats were treated with spinal nerve ligation in 5 days after intraehecal administration.The general behavioral changes and body weight were observed after SNL.At the 7th day after SNL,various does of sinomenine were injected intrathecally to observe the changes of acute pain behavior in rats within 6 hours.At 8 days to 15 days after SNL,rats were injected intrathecally with various does of sinomenine to observe the changes of chronic pain behavior in rats.The rats were sacrificed and taken spinal dorsal horn out on the 15th day after SNL to detect the expression of pain-related protein by molecular biology methods.Results:There was no significant difference in pain behavior between the two groups before and after intrathecal administration(P>0.05).Rats appers paw withdrawal,licking feet and other pain behavior changes after SNL,which does not affect their independent activities.After acute intrathecal injection of various does of sinomenine,the mechanical withdraw threshold(MWT)and thermal withdraw legacy(TWL)were significantly increased as dose-dependent,reaching a peak at 2h after intrathecal administration.Continuous intrathecal administration of sinomenine can continuously alleviate pain symptoms as dose-dependent,which did not find resistant to sinomenine in rats.The results of molecular biology experiments showed that the expressions of glutamate receptor NR1,NR2A,glutamate transporter GLT-1,GLAST,synapsin,synaptophysin,syntaxin and PSD-95 were increased after SNL operation in rats,As well as the expression of Calpain,CDK5 and its activator protein p35/p25.After treatment with different doses of sinomenine and morphine,the above-mentioned various proteins have different degrees of reduction.Conclusion:Our finding suggest that intrathecal adiministration of sinomenine has a significant dose-dependent analgesic effect for SNL-induced neuropathic pain.continuous intrathecal administration of sinomenine will not produce drug resistance.Sinomenine may play a central analgesic effect by regulating the expression of glutamate receptors and related synaptic proteins by regulating CDK5 kinase.