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The role of purinergic signaling in acupuncture-mediated relief of neuropathic and inflammatory pain

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Abstract

Acupuncture is a traditional medicinal practice in China that has been increasingly recognized in other countries in recent decades. Notably, several reports have demonstrated that acupuncture can effectively aid in pain management. However, the analgesic mechanisms through which acupuncture provides such benefits remain poorly understood. Purinergic signaling, which is mediated by purine nucleotides and purinergic receptors, has been proposed to play a central role in acupuncture analgesia. On the one hand, acupuncture affects the transmission of nociception by increasing adenosine triphosphate dephosphorylation and thereby decreasing downstream P2X3, P2X4, and P2X7 receptors signaling activity, regulating the levels of inflammatory factors, neurotrophic factors, and synapsin I. On the other hand, acupuncture exerts analgesic effects by promoting the production of adenosine, enhancing the expression of downstream adenosine A1 and A2A receptors, and regulating downstream inflammatory factors or synaptic plasticity. Together, this systematic overview of the field provides a sound, evidence-based foundation for future research focused on the application of acupuncture as a means of relieving pain.

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Abbreviations

EA:

Electroacupuncture

Glu:

Glutamate

GABA:

γ-Aminobutyric acid

SP:

Substance P

ATP:

Adenosine triphosphate

ADP:

Adenosine diphosphate

AMP:

Adenosine monophosphate

ADO:

Adenosine

R:

Receptor

RA:

Rheumatoid arthritis

eATP:

Extracellular adenosine triphosphate

NF-κB:

Nuclear transcription factor-κB

CCI:

Chronic constriction injury

SNI:

Spared nerve injury

SNL:

Spinal nerve ligation

IBD:

Inflammatory bowel disease

TNBS:

2,4,6-Trinitrobenzene sulfonic acid

L:

Lumbar

CIA:

Collagen-induced arthritis

CFA:

Complete Freund’s adjuvant

MDA:

Malondialdehyde

CRP:

C-reactive protein

GPx:

Glutathione peroxidase

SOD:

Superoxide dismutase

GR:

Glutathione reductase

AP2M:

Adaptor protein-2 complex

CXCR3:

CXC chemokine receptor 3

PAP:

Prostatic acid phosphatase

CGRP:

Calcitonin gene-related peptide

α,β-meATP:

α, β-methylene ATP

STZ:

Streptozotocin

DNP:

Diabetic neuropathic pain

MAPK:

Mitogen-activated protein kinase

TRPV:

Transient receptor potential vanilloid

NTPDases:

Nucleoside triphosphate diphosphohydrolases

NK-1R:

Neurokinin-1 receptor

MCs:

Mast cells

CD73:

Ecto-5′-nucleotidase

AV-shA1RNA:

Short interfering RNA

p:

Phosphorylation

cAMP:

Cyclic adenosine monophosphate

CREB:

Cyclic adenosine monophosphate response element protein

ADA:

Adenosine deaminase

IFN-γ:

Interferon-γ

IL:

Interleukin

TNF-α:

Tumor necrosis factor-α

FKN:

Fractalkine

CX3CR1:

FKN receptor

BDNF:

Brain-derived neurotrophic factor

NTF3:

Neurotrophic-3

RANKL:

NF-κB ligand

PKA:

Protein kinase A

PKC:

Protein kinase C

PMA:

Phorbol 12-myristate 13-acetic acid

ERK:

Extracellular regulated protein kinases

SCDH:

Spinal cord dorsal horn

DRG:

Dorsal root ganglion

HPLC:

High-performance liquid chromatography

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Acknowledgements

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Funding

This work was supported by grants from the National Natural Science Foundation of China (NSFC) (Grant No. 81973944); the Natural Science Foundation of Tianjin (Grant No. 22JCYBJC00990); Youth Talent Promotion Project of the Tianjin Association for Science and Technology (Grant No. TJSQNTJ-2020-15); Innovation Team and Talents Cultivation Program of National Administration of Traditional Chinese Medicine (Grant No. ZYYCXTD-D-202002); Tianjin Graduate Research Innovation Project (Grant No. 2022SKY232); TUTCM Graduate Research Innovation Project (Grant No. YJSKC-20221022).

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Authors and Affiliations

  1. Research Center of Experimental Acupuncture Science, College of Acumox and Tuina, Tianjin University of Traditional Chinese Medicine, Tianjin, 301617, People’s Republic of China

    Mingzhu Huo, Qingxiang Zhang, Yuxin Si, Youlin Zhang, Hongen Chang, Mengmeng Zhou & Yuxin Fang

  2. College of Pharmaceutical Engineering of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, 301617, People’s Republic of China

    Di Zhang

  3. State Key Laboratory of Component-based Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, 301617, People’s Republic of China

    Di Zhang

  4. Haihe Laboratory of Modern Chinese, Tianjin, 301617, People’s Republic of China

    Di Zhang

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  1. Mingzhu Huo
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  2. Qingxiang Zhang
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  3. Yuxin Si
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  4. Youlin Zhang
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  5. Hongen Chang
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  6. Mengmeng Zhou
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  7. Di Zhang
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  8. Yuxin Fang
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DZ and YF were responsible for the conception and design of the study. MH drafted the article. QZ, YS, and YZ were responsible for review and editing. HC and MZ reviewed and critically revised it.

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Huo, ., Zhang, Q., Si, Y. et al. The role of purinergic signaling in acupuncture-mediated relief of neuropathic and inflammatory pain. Purinergic Signalling (2024). https://doi.org/10.1007/s11302-024-09985-y

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