VIP Involved In Amygdala Pain Regulation And Its Mechanism

Pain is a negative sensory experience caused by actual or potential tissue damage to humans and animals.Moderate pain can serve as a warning message to the human body to indicate potential discomfort,but severe and chronic pain not only torments the body but also causes serious psychological damage,leading to various mental illnesses.A large number of studies have shown that the amygdala is an important brain region for pain regulation and plays a key role in connecting pain and emotion.Recent studies have shown that injection of exogenous corticotropin releasing factor(CRF)into the amygdala has obvious analgesic effect,which provides a theoretical basis for neuropeptides to participate in the analgesic effect in the amygdala.Vasoactive intestinal peptide(VIP)and its receptors are widely distributed in the central and peripheral nervous system,and research shows that VIP can participate in neuropathic pain.Therefore,the research purpose of this experiment is to explore and clarify the pain regulation of VIP in the amygdala,and to conduct a preliminary study on its analgesic mechanism,so as to provide a theoretical basis for neuropeptides to play an analgesic role in the central nervous system.The experimental methods were mainly behavioral pain test,intracerebral tube implantation,microinjection,RT-q PCR.Different concentrations of VIP,receptor antagonist,ERK pathway blocker PD98059 and opioid receptor broad-spectrum antagonist naloxone were injected into the amygdala of normal,inflammatory and neuropathic rats The Hindpaw withdrawal latency(HWL)induced by noxious thermal and mechanical stimulation was measured and recorded,and the expression level of VIP receptor m RNA in amygdala were detected.To explore whether VIP has analgesic effect in amygdala and preliminarily study its analgesic mechanism.The experimental results are as follows: After microinjection of VIP with different concentrations into the amygdala,the HWL of normal and chronic pain model rats was significantly prolonged,and the effect was the best at 15 min,and the analgesic effect was dose dependent;The real-time quantitative PCR results showed an increase in the expression levels of VAPC1 and VPAC2,and the injection of receptor antagonist VIP(6-28)could block the analgesic effect of VIP on external stimuli;Injection of ERK pathway blocker PD98059 can inhibit the analgesic effect of VIP;The effect of VIP was blocked by naloxone injection into the amygdala.The injection of VIP increased the pain threshold of chronic pain rat models to nociceptive stimuli,and there was no significant difference in the analgesic effect between chronic pain rats and normal rats.In conclusion,vasoactive intestinal peptide has analgesic effects in the amygdala of normal,inflammatory,and neuropathic rats;Its receptor antagonist can antagonize the effect of vasoactive intestinal peptide,indicating that the analgesic effect is mediated by vasoactive intestinal peptide receptors.Its receptor can participate in the analgesic effect of vasoactive intestinal peptide in the amygdala through the ERK signal pathway,and its analgesic mechanism is also involved in the opioid system...