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Acupuncture modulates extracellular ATP levels in peripheral sensory nervous system during analgesia of ankle arthritis in rats

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Abstract

As an ancient analgesia therapy, acupuncture has been practiced worldwide nowadays. A good understanding of its mechanisms will offer a promise for its rational and wider application. As the first station of pain sensation, peripheral sensory ganglia express pain-related P2X receptors that are involved in the acupuncture analgesia mechanisms transduction pathway. While the role of their endogenous ligand, extracellular ATP (eATP), remains less studied. This work attempted to clarify whether acupuncture modulated eATP levels in the peripheral sensory nerve system during its analgesia process. Male Sprague–Dawley rats underwent acute inflammatory pain by injecting Complete Freund’s Adjuvant in the unilateral ankle joint for 2 days. A twenty-minute acupuncture was applied to ipsilateral Zusanli acupoint. Thermal hyperalgesia and tactile allodynia were assessed on bilateral hind paws to evaluate the analgesic effect. eATP of bilateral isolated lumbar 4-5 dorsal root ganglia (DRGs) and sciatic nerves were determined by luminescence assay. Nucleotidases NTPDase-2 and -3 in bilateral ganglia and sciatic nerves were measured by real-time PCR to explore eATP hydrolysis process. Our results revealed that acute inflammation induced bilateral thermal hyperalgesia and ipsilateral tactile allodynia, which were accompanied by increased eATP levels and higher mechano-sensitivity of bilateral DRGs and decreased eATP levels of bilateral sciatic nerves. Acupuncture exerted anti-nociception on bilateral hind paws, reversed the increased eATP and mechanosensitivity of bilateral DRGs, and restored the decreased eATP of bilateral sciatic nerves. NTPDase-2 and -3 in bilateral ganglia and sciatic nerves were inconsistently modulated during this period. These observations indicate that eATP metabolism of peripheral sensory nerve system was simultaneously regulated during acupuncture analgesia, which might open a new frontier for acupuncture research.

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Data availability

The datasets used or analyzed during the current study are available from the corresponding author on reasonable request.

Abbreviations

ADO:

Adenosine

ADP:

Adenosine diphosphate

AMP:

Adenosine monophosphate

ARL67156:

6-N,N-Diethyl-β-γ-dibromomethylene-D-adenosine-5′-triphosphate

ATP:

Adenosine triphosphate

CFA:

Complete Freund’s Adjuvant

DRG:

Dorsal root ganglia

EAP:

Electric acupuncture

eATP:

Extracellular ATP

exo-ATP:

Exogenous ATP

L-L:

Luciferin-luciferase

Nt5e:

Ecto-5′-nucleotidase

NTPDases:

Nucleoside triphosphate diphosphohydrolases

P2 receptors:

Purinergic receptors

PAP:

Prostatic acid phosphatase

PS:

Physiological solution

PWL:

Paw withdraw latency

PWT:

Paw withdraw threshold

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Acknowledgements

This research was financially supported by National Natural Science Foundation of China (Grant No. 81574076, to L-N W, 8159950026 to D Z). We like to thank Prof. Ryszard Grygorczyk (Université de Montréal, Montreal, Canada) and Prof. Wolfgang Schwarz (Goethe-University, Frankfurt, Germany) for revising the paper.

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Funding

National Natural Science Foundation of China (Grant No. 81574076, to L-N W and 8159950026 to D Z).

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Authors and Affiliations

  1. School of Acupuncture-Moxibustion and Tuina, Shanghai University of Traditional Chinese Medicine, 1200 Cailun Road, Shanghai, 201203, China

    Dan Shen, Ya-Wen Zheng, Xue-Yong Shen & Li-Na Wang

  2. School of Traditional Chinese Medicine, Naval Medical University, 800 Xiangyin Road, Shanghai, 200433, China

    Dan Shen

  3. Shanghai Key Laboratory of Acupuncture Mechanism and Acupoint Function (14DZ2260500), Fudan University, 220 Handan Road, Shanghai, 201433, China

    Di Zhang

  4. Department of Aeronautics and Astronautics, Fudan University, 220 Handan Road, Shanghai, 200433, China

    Di Zhang

  5. Shanghai Research Center for Acupuncture and Meridians, Shanghai, 201203, China

    Xue-Yong Shen & Li-Na Wang

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  1. Dan Shen
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  3. Di Zhang
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  4. Xue-Yong Shen
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Contributions

Conceptualization by Li-Na WANG and Xue-Yong SHEN; data collection by Dan SHEN and Ya-Wen ZHENG; data analysis by Dan SHEN; figure formation by Di ZHANG; data interpretation by Li-Na WANG; first manuscript writing by Dan SHEN; manuscript revision by Li-Na WANG and Xue-Yong SHEN. All authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

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Correspondence to Xue-Yong Shen or Li-Na Wang.

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All experimental protocols were approved by the Animal Care Committee of Shanghai University of Traditional Chinese Medicine (Shanghai, China) (No SZY201807008).

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Shen, D., Zheng, YW., Zhang, D. et al. Acupuncture modulates extracellular ATP levels in peripheral sensory nervous system during analgesia of ankle arthritis in rats. Purinergic Signalling 17, 411–424 (2021). https://doi.org/10.1007/s11302-021-09777-8

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