Table_1_Role of Neuroimmune Crosstalk in Mediating the Anti-inflammatory and Analgesic Effects of Acupuncture on Inflammatory Pain.DOCX

Inflammatory pain is caused by peripheral tissue injury and inflammation. Inflammation leads to peripheral sensitization, which may further cause central sensitization, resulting in chronic pain and progressive functional disability. Neuroimmune crosstalk plays an essential role in the development and maintenance of inflammatory pain. Studies in recent years have shown that acupuncture can exert anti-inflammatory and analgesic effects by regulating peripheral (i.e., involving local acupoints and inflamed regions) and central neuroimmune interactions. At the local acupoints, acupuncture can activate the TRPV1 and TRPV2 channels of mast cells, thereby promoting degranulation and the release of histamine, adenosine, and other immune mediators, which interact with receptors on nerve endings and initiate neuroimmune regulation. At sites of inflammation, acupuncture enables the recruitment of immune cells, causing the release of opioid peptides, while also exerting direct analgesic effects via nerve endings. Furthermore, acupuncture promotes the balance of immune cells and regulates the release of inflammatory factors, thereby reducing the stimulation of nociceptive receptors in peripheral organs. Acupuncture also alleviates peripheral neurogenic inflammation by inhibiting the release of substance P (SP) and calcitonin gene-related peptide from the dorsal root ganglia. At the central nervous system level, acupuncture inhibits the crosstalk between glial cells and neurons by inhibiting the p38 MAPK, ERK, and JNK signaling pathways and regulating the release of inflammatory mediators. It also reduces the excitability of the pain pathway by reducing the release of excitatory neurotransmitters and promoting the release of inhibitory neurotransmitters from neurons and glial cells. In conclusion, the regulation of neuroimmune crosstalk at the peripheral and central levels mediates the anti-inflammatory and analgesic effects of acupuncture on inflammatory pain in an integrated manner. These findings provide novel insights enabling the clinical application of acupuncture in the treatment of inflammatory diseases.

炎症性疼痛（Inflammatory pain）由外周组织损伤（peripheral tissue injury）与炎症引发。炎症可诱导外周敏化（peripheral sensitization），进而可进一步引发中枢敏化（central sensitization），最终导致慢性疼痛与进行性功能障碍。神经免疫互作（neuroimmune crosstalk）在炎症性疼痛的发生与维持过程中发挥关键作用。近年来的研究表明，针灸可通过调控外周（peripheral，即涉及局部穴位与炎症区域）及中枢神经免疫互作，发挥抗炎镇痛作用。在局部穴位处，针灸可激活肥大细胞的TRPV1与TRPV2通道，促进其脱颗粒并释放组胺、腺苷等免疫介质，这些介质与神经末梢上的受体结合，启动神经免疫调控程序。在炎症部位，针灸可招募免疫细胞，促使其释放阿片肽，同时还可通过神经末梢发挥直接镇痛作用。此外，针灸能够促进免疫细胞稳态平衡，调控炎症因子释放，从而减轻外周器官伤害性感受器所受的刺激。针灸还可通过抑制背根神经节（dorsal root ganglia）释放P物质（substance P，SP）与降钙素基因相关肽（calcitonin gene-related peptide），缓解外周神经源性炎症。在中枢神经系统（central nervous system）层面，针灸可通过抑制p38丝裂原活化蛋白激酶（p38 MAPK）、细胞外调节蛋白激酶（ERK）与c-Jun氨基末端激酶（JNK）信号通路，调控炎症介质释放，进而抑制胶质细胞（glial cells）与神经元（neurons）之间的互作。此外，针灸可减少神经元与胶质细胞释放兴奋性神经递质（excitatory neurotransmitters），促进抑制性神经递质（inhibitory neurotransmitters）的释放，降低疼痛传导通路的兴奋性。综上，针灸通过在外周与中枢层面调控神经免疫互作，以整合式的机制介导其针对炎症性疼痛的抗炎镇痛作用。上述研究发现为针灸在炎症性疾病治疗中的临床应用提供了全新的研究视角与实践方向。