生长抑素II型受体镇痛作用的机制研究

神经病理性疼痛是慢性疼痛中普遍发生的一种病理症状，外周神经损伤是诱发神经病理性疼痛的原因之一。本研究前期发现生长抑素II型受体（SST2）激动剂-奥曲肽（Oct），对神经病理性疼痛具有镇痛作用。本项目在此基础上，拟基于神经损伤诱发的病理性疼痛模型，观察奥曲肽（Oct）处理后，内源性生长抑素（SOM）及其SST2受体的表达和功能的变化；通过检测SST2特异性激动剂和拮抗剂的处理对小鼠疼痛行为学的影响和背根神经节（DRG）神经元内，SST2对内源性致痛系统--p38 MAPK信号通路的拮抗作用以及与SST2相关分子的差异表达情况，探究此过程中神经元的可塑性调节机制，以而论证SOM通过作用其SST2受体发挥镇痛作用的假说；继而探讨其调节神经病理性疼痛的分子机制，为防治或研发新型镇痛药提供新策略。

Neuropathic pain is common and severe chronic pain originating from peripheral nerve injury. In our previous work, we found that Octreotide(Oct) ,the somatostatin(SOM) analogue as well as the specific agonist of somatostatin receptor-2 (SST2), potentially inhabits neuropathic pain.Based on the previous results, SST2 receptors may be related to the analgesic effect of SOM. In this research, we aimed at detecting the changes of painful behavior and differential expression of neuropeptide as well as important signal transduction molecules that were of relevance in neuropathic pain on the basis of spared nerve injury model. Furthermore, the inhibitory effect of p38MAPKs pathway and the differential expression of some important molecules related to SST2 were examined as well as the regulation of neuroplasticity after the SST2 agonist and antagonist treatment to elucidate our current hypothesis mechanisms of the analgesic function of SOM-SST2 that may offer a new and effective target for the treatment of neuropathic pain.