癌痛是影响癌症患者生活质量的主要原因，以骨癌痛为多见。癌痛发生机制错综复杂，临床治疗主要依赖阿片药物，缺乏针对性治疗。电针已被用于癌痛治疗，其作用机制仍不清楚。本项目采用胫骨内注射MRMT-1乳腺癌细胞建立骨癌痛大鼠模型，检测大鼠缩足阈、足底注射P2X3受体拮抗/激动剂诱发缩足反应及电针干预，观察外周P2X3受体在电针抗骨癌痛中的作用；检测骨癌痛大鼠DRG中P2X3受体膜/总蛋白比、P2X3受体与细胞膜标记物共表达和α,β-meATP诱发神经元电流变化及电针干预，观察DRG P2X3受体膜表达变化在骨癌痛外周敏化和电针镇痛的作用；鞘内注射shRNA慢病毒实现CASK基因沉默，观察骨癌痛大鼠CASK与P2X3受体共存和结合情况及电针干预，探讨电针调节P2X3受体去膜锚定的CASK调控机制。通过本项目研究，从新的角度揭示电针抗骨癌痛的作用机理，为推动电针疗法在难治性疼痛的应用提供科学研究基础。

Cancer pain, especially bone cancer pain, greatly influences quality of life in cancer patients. The mechanism of cancer pain is complicated while cancer pain is usually controlled by opioid analgesics in the clinic due to lack of targeted therapy. Electroacupuncture (EA) has been used clinically to treat cancer pain, however, its mechanism is still unclear. In this study, bone cancer pain were established by intra-tibia injection of MRMT-1 mammary gland carcinoma cells. By measuring the changes of paw withdrawal thresholds as well as paw flinching reflexes induced by intraplantar injection of specific P2X3 receptor antagonist (A-317491) and agonist (α,β-meATP), to explore the role of P2X3 receptor played in the analgesic effect of EA on bone cancer pain. By detecting the expression and ratio of membrane and total P2X3 protein, co-location of P2X3 receptor and plasma membrane marker in DRG and current responses to α,β-meATP in DRG neurons as well as EA’s intervention, to further observe whether changes of P2X3 receptor expression in DRG neuron membrane participated in peripheral sensitization of bone cancer pain and EA’s analgesia. Using intrathecal injection of shRNA lentivirus to slience calcium/calmodulin-dependent serine protein kinase (CASK) gene, the intervention of EA on co-location and co-expression between CASK and P2X3 receptor were investigated. We further clarify EA decreasing membrane expression of P2X3 receptor and its mechanism via regulating CASK. The results of this project may elucidate the novel mechanism of EA on bone cancer pain, which contribute to the enrichment of EA’s analgesic mechanism and widespread application of EA on treating refractory pain.