Purinergic signaling as a basis of acupuncture-induced analgesia
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REVIEW ARTICLE
Purinergic signaling as a basis of acupuncture-induced analgesia Jin-Rong He 1 & Shu-Guang Yu 1,2 & Yong Tang 1,2 & Peter Illes 1,3 Received: 26 March 2020 / Accepted: 2 June 2020 # The Author(s) 2020
Abstract This review summarizes experimental evidence indicating that purinergic mechanisms are causally involved in acupuncture (AP)-induced analgesia. Electroacupuncture (EAP) and manual AP release at pain-relevant acupoints ATP which may activate purinergic P2X receptors (Rs) especially of the P2X3 type situated at local sensory nerve endings (peripheral terminals of dorsal root ganglion [DRG] neurons); the central processes of these neurons are thought to inhibit via collaterals of ascending dorsal horn spinal cord neurons, pain-relevant pathways projecting to higher centers of the brain. In addition, during AP/EAP nonneuronal P2X4 and/or P2X7Rs localized at microglial cells of the CNS become activated at the spinal or supraspinal levels. In consequence, these microglia secrete bioactive compounds such as growth factors, cytokines, chemokines, reactive oxygen, and nitrogen species, which modulate the ascending neuronal pathways conducting painful stimuli. Alternatively, ATP released at acupoints by AP/EAP may be enzymatically degraded to adenosine, stimulating in loco presynaptic A1Rs exerting an inhibitory influence on the primary afferent fibers (the above mentioned pain-sensing peripheral terminals of DRG neurons) which thereby fail to conduct action potentials to the spinal cord dorsal horn. The net effect of the stimulation of P2X3, P2X4, P2X7, and A1Rs by the AP/EAP-induced release of ATP/adenosine at certain acupoints will be analgesia. Keywords Acupuncture . Electroacupuncture . ATP . Adenosine . P2X receptors . P2Y receptors . P1/A1 receptors
Abbreviations AP ASIC3 Bz-ATP CCI CCPA
Acupuncture Acid-sensing ion channel 3 Dibenzoyl-ATP Chronic constriction injury 2-Chloro-N6-cyclopentyl-adenosine
* Peter Illes [email protected] Jin-Rong He [email protected] Shu-Guang Yu [email protected] Yong Tang [email protected] 1
International Collaborative Centre on Big Science Plan for Purine Signalling, Chengdu University of Traditional Chinese Medicine, Chengdu 610075, China
2
Acupuncture & Chronobiology Key Laboratory of Sichuan Province, Chengdu 610075, China
3
Rudolf Boehm Institute for Pharmacology and Toxicology, University of Leipzig, 04107 Leipzig, Germany
CFA CPX DRG EAP fEPSP GABAA-R IFN-γ IL-1β PAP P2XR P2YR R TRPV1 α,β-meATP
Complete Freund’s adjuvant 8-Cyclopentyl-1,3-dipropylxanthine Dorsal root ganglion Electroacupuncture Field excitatory postsynaptic potential γ-Aminobutyric acid receptor A Interferon-γ Interleukin-1β Prostatic acid phosphatase Purinergic ligand-gated cationic channel Purinergic G protein-coupled receptor Receptor Transient receptor potential vanilloid 1 α,β-methylene ATP
Introduction Acupuncture (AP) is a therapeutic manipulation of traditional Chinese medicine, known for the past 3000 to 4000 years [1, 2]. Nowadays, acupuncture refers
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