Mechanosensitive TRPV4 Channel-Induced Extracellular ATP Accumulation at the Acupoint Mediates Acupuncture Analgesia of Ankle Arthritis in Rats

• Main Authors: Yawen Zheng, Weimin Zuo, Dan Shen, Kaiyu Cui, Meng Huang, Di Zhang, Xueyong Shen, Lina Wang
• Format: Article
• Language: English
• Published: MDPI AG 2021-05-01
• Series: Life
• Subjects: acupuncture analgesia; mechano-sensitivity; TRPV4; extracellular ATP; nucleotidases
• Online Access: https://www.mdpi.com/2075-1729/11/6/513

(1)<b> </b>Background<i>: </i>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<i>: </i>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<i>:</i> AP analgesic effect was significantly suppressed by pre-injection of GdCl₃ 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<i>:</i> 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.