Research On The Analgesic Effect Of Substance P In Dorsal Raphe Nucleus（DRN） Of Rats

Objective: To explore the analgesic effect of exogenous substance P in dorsal raphe nucleus（DRN）of rats.Methods: The rat models of chronic pain,hypertension and depresson were established by behavioral pain measurement.Different concentrations of substance P,Aprepitant（NK-1 receptor antagonist）,chelerythrine（PKC pathway blocker）and naloxone（opioid receptor broad-spectrum antagonist）were separately injected into DRN of normal and model rats.The hindpaw withdrawal latency（HWL）to mechanical and nociceptive thermal stimulation as the indicators of pain measurement were further recorded,in order to explore whether substance P has analgesic effect in DRN,and whether NK-1 receptor and opioid system are involved in its mechanism of analgesic effect.Results: Different concentrations of substance P were injected into DRN of normal and model rats,and the hindpaw withdrawal latency to mechanical and nociceptive thermal stimulation prolonged,indicating that substance P was involved in the analgesic effect in DRN of rats.Specifically,the best analgesic effect appeared on 15 min after injection.After comparison,it was found that there was no significant difference in the analgesic effect of substance P between normal and model rats.Simultaneous injection of substance P and SPA into DRN of normal rats and model rats of inflammatory pain could partially block the analgesic effect of substance P.Injection of chelerythrine（PKC pathway blocker）inhibited the analgesic effect of substance P,suggesting that the analgesic mechanism of substance P is related to the pathway mediated by G protein,indicating that NK-1 receptor of substance P is involved in the analgesic effect in DRN of rats.Injection of naloxone could inhibit the effect of substance P on feeding activity and block the analgesic effect of substance P,indicating that opioid receptor is involved in the analgesic effect of substance P.Conclusion: Substance P is involved in the pain regulation in DRN of normal and model rats,that is,it has analgesic effect.The mechanism of this analgesic effect is involved in the PKC pathway and is related to the binding of NK-1 receptor and opioid receptor.