Zheng Yawen, Zuo Weimin, Shen Dan, Cui Kaiyu, Huang Meng, Zhang Di, Shen Xueyong, Wang Lina
Acupuncture and Moxibustion College, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China.
Shanghai Research Center for Acupuncture and Meridians, Shanghai 201203, China.
Life (Basel). 2021 May 31;11(6):513. doi: 10.3390/life11060513.
(1) Background Acupuncture (AP) is a safe and effective analgesic therapy. Understanding how fine needles trigger biological signals can help us optimize needling manipulation to improve its efficiency. Adenosine accumulation in treated acupoints is a vital related event. Here, we hypothesized that extracellular ATP (eATP) mobilization preceded adenosine accumulation, which involved local activation of mechanosensitive channels, especially TRPV4 protein. (2) Methods AP was applied at the injured-side Zusanli acupoint (ST36) of acute ankle arthritis rats. Pain thresholds were assessed in injured-side hindpaws. eATP in microdialysate from the acupoints was determined by luminescence assay. (3) Results AP analgesic effect was significantly suppressed by pre-injection of GdCl or ruthenium red in ST36, the wide-spectrum inhibitors of mechanosensitive channels, or by HC067047, a specific antagonist of TRPV4 channels. Microdialysate determination revealed a needling-induced transient eATP accumulation that was significantly decreased by pre-injection of HC067047. Additionally, preventing eATP hydrolysis by pre-injection of ARL67156, a non-specific inhibitor of ecto-ATPases, led to the increase in eATP levels and the abolishment of AP analgesic effect. (4) Conclusions These observations indicate that needling-induced transient accumulation of eATP, due to the activation of mechanosensitive TRPV4 channels and the activities of ecto-ATPases, is involved in the trigger mechanism of AP analgesia.
（1）背景：针灸是一种安全有效的镇痛疗法。了解细针如何触发生物信号有助于我们优化针刺手法以提高其疗效。治疗穴位中腺苷的积累是一个至关重要的相关事件。在此，我们假设细胞外ATP（eATP）的动员先于腺苷的积累，这涉及机械敏感通道的局部激活，尤其是TRPV4蛋白。（2）方法：对急性踝关节关节炎大鼠的患侧足三里穴（ST36）进行针灸。评估患侧后爪的疼痛阈值。通过发光测定法测定穴位微透析液中的eATP。（3）结果：在ST36预先注射机械敏感通道的广谱抑制剂GdCl或钌红，或TRPV4通道的特异性拮抗剂HC067047，可显著抑制针灸的镇痛效果。微透析液测定显示针刺诱导的eATP短暂积累，预先注射HC067047可使其显著降低。此外，预先注射胞外ATP酶的非特异性抑制剂ARL67156以阻止eATP水解，导致eATP水平升高并消除了针灸的镇痛效果。（4）结论：这些观察结果表明，由于机械敏感的TRPV4通道的激活和胞外ATP酶的活性，针刺诱导的eATP短暂积累参与了针灸镇痛的触发机制。
