三叉神经尾核（TNC）“中枢致敏”是慢性偏头痛(CM)转化的关键，确切机制不明。NR2B磷酸化触发突触可塑性LTP的形成和维持是慢性疼痛中枢致敏的病理基础。我们已报道下调三叉神经节PTEN缓解偏头痛的机制可能与PTEN降低NR2B的神经兴奋性及CREB调控的LTP有关，预实验发现CM大鼠TNC区神经元有PTEN和NR2B-pTyr表达升高，我们推测CM可能因PTEN升高导致NR2B磷酸化和CREB增加触发LTP所致。为阐明PTEN所介导的NR2B磷酸化/CREB通路在维持偏头痛慢性化中的作用，本课题拟在CM大鼠模型上，转染PTEN腺病毒，用分子生物学、行为学及膜片钳等技术，测相关脑区PTEN、NR2B磷酸化、CREB等的表达、鼠行为学及电生理等改变，本研究将回答CM转化机制可能是由PTEN激活NR2B磷酸化和CREB升高触发LTP引起的“中枢致敏”所致这一科学问题，也可为CM防治提供新靶点

Central sensitization in the trigeminal nucleus caudalis(TNC) is a key of transformation of chronic migraine(CM), but precise mechanism is not known yet. Phosphorylation of the NR2B subunit of the NMDA receptor triggering formation and maintenance of Long-term potentiation (LTP) of synaptic plasticity is the pathological foundation of central sensitization in chronic pain. We had reported that downregulation PTEN in the trigeminal ganglia of rats with nitroglycerin-induced migraine may alleviate migraine attack, its mechanisms is likely to associated with PTEN reducing neuronal excitability at NR2B and CREB(cAMP response element-binding protein)-modulated LTP level. Meanwhile, our preliminary result found that there was increase of PTEN and NR2B-pTyr1472 and CREB expression in neurons within TNC of chronic migraine rats induced by Inflammatory Soup(IS). Then, we speculate that elevation of PTEN causing high level of NR2B phosphorylation and CREB may trigger LTP resulting in chronic migraine. To illuminate PTEN-mediated “PTEN/NR2B-phospho/CREB” signal pathway participate the maintenance of the chronification of migraine in rats, this study will plan to establish SD rats model of CM with IS and NOC-18, and transfected PTEN gene adenovirus, then the expression of PTEN , NR2B-phospho, CREB as well as electrophysiology and the behavioral change were measured by QT-PCR, Western blotting, von Frey monofilament and patch clamp et al. These results will be able to answer a scientific problem, that is, the transformed mechanisms of chronic migraine may be due to central sensitization induced by PTEN causing the increase of NR2B-phospho and CREB triggering LTP, which will find novel targets for prevention and therapy of chronic migraine.