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

被引:22
作者
Zheng, Yawen [1 ]
Zuo, Weimin [1 ]
Shen, Dan [1 ]
Cui, Kaiyu [1 ]
Huang, Meng [2 ]
Zhang, Di [3 ]
Shen, Xueyong [1 ,2 ]
Wang, Lina [1 ,2 ]
机构
[1] Shanghai Univ Tradit Chinese Med, Acupuncture & Moxibust Coll, Shanghai 201203, Peoples R China
[2] Shanghai Res Ctr Acupuncture & Meridians, Shanghai 201203, Peoples R China
[3] Fudan Univ, Shanghai Key Lab Acupuncture Mech & Acupoint Func, Dept Aeronaut & Astronaut, Shanghai 200433, Peoples R China
来源
LIFE-BASEL | 2021年 / 11卷 / 06期
基金
中国国家自然科学基金;
关键词
acupuncture analgesia; mechano-sensitivity; TRPV4; extracellular ATP; nucleotidases; MOUSE SKELETAL-MUSCLE; ECTO-5'-NUCLEOTIDASE CD73; CATION CHANNEL; CA2+ INFLUX; NOCICEPTION; ADENOSINE; RELEASE; ROLES; ADENOSINE-A1-RECEPTORS; STIMULATION;
D O I
10.3390/life11060513
中图分类号
Q [生物科学];
学科分类号
07 ; 0710 ; 09 ;
摘要
(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 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: 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.
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页数:14
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