sTREM2介导小胶质细胞-神经元“对话”在脉冲射频改善神经病理性疼痛中的机制研究

神经病理性疼痛(NP)是临床棘手问题。脉冲射频（PRF）显著改善NP，但机制不明。小胶质细胞-神经元“对话”失调在神经疾病中备受关注，最新发现可溶型TREM2（sTREM2）是调节 “对话”的关键。那么PRF是否通过sTREM2调控小胶质细胞-神经元对话改善NP？前期发现:①坐骨神经损伤大鼠脊髓背角sTREM2及其催化酶ADAM17表达增加;②sTREM2促进神经炎及AMPAR活化;③PRF抑制sTREM2及ADAM17表达。据此提出：PRF通过抑制ADAM17酶催化的sTREM2表达，抑制神经炎和脊髓背角长时程增强（LTP），干扰小胶质细胞与神经元对话以减轻疼痛。我们拟用神经电生理、条件性基因敲除等方法，探究PRF对sTREM2表达调控，理清sTREM2在PRF抑制神经炎症和LTP中的作用，揭示PRF通过抑制小胶质细胞-神经元对话发挥抗炎镇痛的分子机制，为PRF治疗NP提供新的理论依据。

Neuropathic pain (NP) is a difficult clinical problem. Pulsed Radiofrequency (PRF) significantly attenuates NP, but the mechanism remains unclear. The dysregulation of microglia-neuron “crosstalk” has attracted much attention in neurological diseases，and soluble TREM2 (sTREM2) is lately found to be the core in the “crosstalk”. Therefore, we raised the following scientific question: Does PRF improve NP by regulating microglia-neuron “crosstalk" through sTREM2? Our previous work showed that 1) the expression of sTREM2 and its catalytic enzyme ADAM17 increased in the spinal dorsal horn of spared nerve injury (SNI) rats; 2) sTREM2 promoted the occurrence of neuroinflammatory response and the activation of AMPA receptors; 3) PRF inhibited the expression of sTREM2 and ADAM17. Therefore, we propose the following scientific hypothesis: PRF inhibits neuroinflammation and spinal dorsal horn long-term potentiation (LTP) by inhibiting the ADAM17-catalyzed expression of sTREM2, and thereby interrupting the crosstalk between microglia and neurons to exert analgesic effects. We intend to use electrophysiological, conditional gene knockout and other methods to explore the regulation of PRF on sTREM2 expression, clarify the role of sTREM2 in the inhibition of neuroinflammation and LTP by PRF, and reveal the molecular mechanism of anti-inflammatory and analgesic effect of PRF by inhibiting the crosstalk between microglia and neurons, which aims to add a new theoretical basis for the treatment of PRF in NP.