Teoh Boon Khai, Romero Sharmely Sharon Ballon, Quach Tran Van Bao, Chung Hsin-Yi, Chen Yi-Hung
Graduate Institute of Acupuncture Science, China Medical University, No. 91, Hsueh-Shih Road, Taichung 404328, Taiwan.
International Master Program in Integrative Health, China Medical University, Taichung City 404328, Taiwan.
Brain Sci. 2025 Jul 31;15(8):822. doi: 10.3390/brainsci15080822.
Heat therapy (HT) and electroacupuncture (EA) are widely utilized pain relief methods, but the analgesic mechanisms of their combined application remain unclear. In acetic acid (AA)-induced writhing test and complete Freund's adjuvant (CFA)-induced inflammatory pain tests, mice received one of three treatments: EA at bilateral ST36, HT via a 45 °C heating pad, or the combination (EA + HT). To probe underlying pathways, separate groups were pretreated with caffeine, DPCPX (a selective adenosine A receptor antagonist), or naloxone (an opioid receptor antagonist). Spinal expression of glial fibrillary acidic protein (GFAP) and phosphorylated p38 (p-p38) was examined by Western blot and immunofluorescence. Both EA and HT individually reduced AA-induced writhing, with the combination (EA + HT) exhibiting the greatest analgesic effect. EA's analgesic effect was reversed by caffeine and DPCPX and partially by naloxone, while HT's effect was reversed by caffeine and DPCPX but was unaffected by naloxone. AA injection elevated spinal p-p38 and GFAP expression, which were attenuated by either EA or HT, with the most substantial suppression observed in the EA + HT group. In the CFA model, both treatments alleviated mechanical allodynia, while the combined treatment resulted in significantly greater analgesia compared to either treatment alone. EA combined with HT synergistically enhances analgesia in both AA and CFA pain models, accompanied by reduced spinal inflammation and astrocyte activation. EA's analgesic effects appear to involve adenosine A receptor pathways and, to a lesser extent, opioid receptor mechanisms, whereas HT's effects involve adenosine A receptor pathways.
热疗法（HT）和电针疗法（EA）是广泛应用的止痛方法，但其联合应用的镇痛机制尚不清楚。在醋酸（AA）诱导的扭体试验和完全弗氏佐剂（CFA）诱导的炎性疼痛试验中，小鼠接受三种治疗之一：双侧足三里电针、通过45℃加热垫进行热疗或联合治疗（电针+热疗）。为探究潜在途径，单独的组用咖啡因、DPCPX（一种选择性腺苷A受体拮抗剂）或纳洛酮（一种阿片受体拮抗剂）进行预处理。通过蛋白质免疫印迹法和免疫荧光法检测脊髓胶质纤维酸性蛋白（GFAP）和磷酸化p38（p-p38）的表达。电针和热疗单独应用均能减少醋酸诱导的扭体反应，联合治疗（电针+热疗）镇痛效果最佳。咖啡因和DPCPX可逆转电针的镇痛作用，纳洛酮可部分逆转其作用；而咖啡因和DPCPX可逆转热疗的作用，但纳洛酮对其无影响。注射醋酸可提高脊髓p-p38和GFAP的表达，电针或热疗均可使其减弱，电针+热疗组的抑制作用最为显著。在CFA模型中，两种治疗均能减轻机械性异常性疼痛，联合治疗比单独任何一种治疗的镇痛效果都显著增强。电针与热疗联合应用可协同增强醋酸和CFA疼痛模型中的镇痛作用，同时减轻脊髓炎症和星形胶质细胞活化。电针的镇痛作用似乎涉及腺苷A受体途径，在较小程度上涉及阿片受体机制，而热疗的作用则涉及腺苷A受体途径。
