神经病理痛可由创伤、神经变性等多种疾病导致，严重困扰患者，目前仍缺乏有效治疗手段。前期工作中，我们发现Mu型阿片受体（MOR）外周激动剂（DALDA）能缓解神经病理痛大鼠诱发和自发痛行为，但大剂量反复使用后会引起耐受，严重降低其镇痛效果。研究亦证实背根神经节（DRG）神经元上的大麻素1型受体（CB1R）参与痛觉调节，且其与MOR在体外可以形成复合体。根据以上研究基础，我们拟利用野生型和转基因小鼠神经病理痛模型，明确神经损伤后MOR和CB1R在DRG神经元上的共定位和相互作用；探究DALDA与CB1R外周激动剂联合应用的镇痛效果，以及潜在的神经生理学机制；进一步利用分子生物学实验在体外细胞上揭示MOR-CB1R复合体影响MOR激动剂镇痛效能的关键分子机制和信号通路。此项研究成果将丰富人们对体内MOR-CB1R复合体存在和功能的认识，为治疗神经病理痛提供新的用药策略和治疗靶点。

Neuropathic pain can be caused by a variety of diseases, such as trauma and neurodegeneration. In the previous work, we found that Mu opioid receptor (MOR) peripheral agonist (DALDA) could alleviate the evoked and spontaneous pain behavior in nerve-injured rats, but the repeated administration of high-dose DALDA lead to analgesia tolerance. Cannabinoid type 1 (CB1) receptors co-express with MOR in dorsal root ganglion (DRG) neurons, and they can form a complex in vitro. In current study, by using neuropathic pain models of wild-type (WT) and transgenic (CB1-/-, etc.) mice, we will clarify the co-localization and interaction of MOR and CB1R on DRG neurons after nerve injury; to explore the synergistic analgesia of DALDA and CB1 peripheral agonist and the underlying neurophysiological mechanisms; to investigate the substantial molecules and signaling pathways of MOR-CB1R complex enhancing the analgesic efficacy of MOR agonist by in vitro experiments. This study will enrich people's understanding and knowledge of the expression and function of MOR-CB1R complex in vivo, and provide new therapeutic strategies and targets for the treatment of neuropathic pain.