我们前期研究显示，脊髓TREM2/DAP12介导小胶质细胞持续活化，参与顺铂化疗小鼠外周神经病变。文献表明，电针可以调节脊髓小胶质细胞功能发挥镇痛作用；化疗会引起神经元凋亡，而损伤的神经元TREM2-L表达增加。我们前期工作显示，电针通过上调脊髓GRK2/Epac1比值，调节脊髓小胶质细胞M1/M2型比值抗炎镇痛；在顺铂化疗小鼠模型上，电针可缓解外周神经病变，下调脊髓TREM2和小胶质细胞Iba1，且能上调脊髓GRK2。那么，脊髓GRK2/Eapc1是否参与顺铂化疗性外周神经病变呢？电针又是否通过脊髓GRK2/Eapc1来调节TREM2/DAP12小胶质细胞活化分型来缓解顺铂化疗性外周神经病变呢？本项目拟以TREM2/DAP12调节小胶质细胞活化分型为切入点，研究脊髓GRK2/Eapc1在顺铂化疗致外周神经病变以及电针缓解作用中的机制，来深入理解化疗致外周神经病变及针刺作用的内在机理。

Our previous work shown that cisplatin triggered persistent activation of spinal cord microglia through strengthening the triggering receptor expressed on myeloid cells 2 (TREM2)/DNAX-activating protein of 12 kDa (DAP12) signaling, which further resulted in chemotherapy induced peripheral neuropathy. It has been demonstrated that electroacupuncture (EA) analgesia by regulating spinal microglial functions; Chemotherapy increased neuronal apoptosis, and the injuried neuron increased TREM2-Ligands expression. Our previous work also shown that EA analgesia on inflammatory pain by increasing the spinal G Protein Coupled Receptor Kinase 2 (GRK2)/exchange protein activated by cAMP (Epac1) ratio, subsequently regulating the microglial phenotype M1/M2; in cisplatin treated mice, EA alleviated cisplatin induced peripheral neuropathy (pain and numbness), decreased spinal TREM2 and microglial marker-Iba1, and increased spinal GRK2 level. Hence, the present study was designed to investigate the role of spinal GRK2/Epac1 regulating microglial phenotype in cisplatin induced peripheral neuropathic pain and numbness, and the mechanisms underlie the protective effects of EA on cisplatin induced peripheral neuropathy. This study will help to further understand the mechanisms underlie peripheral neuropathic pain and numbness associated with chemotherapy and the neuroprotective effects by acupuncture.