电针-米那普仑联用介导GABA重塑蓝斑-脊髓环路的镇痛机制研究

Chronic neuropathic pain causes depression, which aggravates the pain. Neuropathic pain has become a major public health problem. Studies have shown that locus coeruleus-spinal cord（LC-SC） circuit plays an important role in regulating pain and depression. In our previous studies, we found the effective site of enhanced analgesia of co-application of electroacupuncture (EA) and milnacipran (a new antidepressant drug) is spinal cord. We hypothesize that the enhanced analgesic effects of co-application of EA and milnacipran, may be related to remodeling of LC-SC circuit by GABA release from interneurons. This study consists of four parts: molecule, cell, tissue and animal behavior. Using ELISA, RT-PCR, HPLC, IF and whole-cell patch clamp techniques, and using animal behavioral measurement methods, from molecular, cellular, tissue and animal behavioral levels, to obtain the evidence that can confirm the hypothesis, in brain stem descending inhibitory system which initiated from LC and ended in SC dorsal horn. This study will provide a theoretical basis and new ideas for clinical promotion of EA-milnacipran combination therapy for neuropathic pain accompanied by depression.

慢性神经病理性疼痛（神经痛）引发抑郁，抑郁使神经痛加剧，神经痛已成为一个重大公共卫生难题，研究表明蓝斑-脊髓环路协同调控疼痛和抑郁。课题组在证实电针-米那普仑（抗抑郁新药）协同镇痛有效部位是脊髓的基础上，本研究以蓝斑-脊髓环路重塑为视角，沿着电针-米那普仑联用介导GABA重塑神经环路的思路，朝着系统阐述蓝斑-脊髓环路重塑产生协同镇痛作用的目标开展工作。研究由分子、细胞、组织以及动物行为学四个部分构成，应用ELISA、RT-PCR、HPLC、IF和全细胞膜片钳等技术，运用动物行为学检测等方法，从分子、细胞、组织以及动物行为学多层次，在脑干蓝斑为起始、脊髓背角为终点的下行抑制环路中，获取电针-米那普仑联用介导GABA重塑蓝斑-脊髓神经环路的相关证据，阐明电针-米那普仑协同镇痛作用的神经环路重塑机制。本研究将为临床推广电针-米那普仑联用治疗伴抑郁的神经痛提供理论依据和新的思路。

慢性神经病理性疼痛（神经痛）引发抑郁，抑郁使神经痛加剧，神经痛已成为一个重大公共卫生难题，研究表明蓝斑-脊髓环路协同调控疼痛和抑郁。课题组在通过动物行为学和药理学检测，证实电针-米那普仑（抗抑郁新药）协同镇痛有效部位是脊髓的基础上，结合分子生物学，采用ELISA、RT-PCR、Western blot、IF和等技术，在脑干蓝斑为起始、脊髓背角为终点的下行抑制环路中，获取电针-米那普仑联用介导GABA重塑蓝斑-脊髓神经环路的相关证据，阐明电针-米那普仑协同镇痛作用的神经环路重塑机制。结果初步证实电针和米那普仑的协同镇痛作用和脊髓内 NE-a2a 受体的激活相关；证实电针-小剂量米那普仑联用介导 GABA 重塑脊髓局部环路产生协同镇痛作用。本研究将为临床推广电针-米那普仑联用治疗伴抑郁的神经痛提供理论依据和新的思路。.