1. Academic Validation
  2. Manual acupuncture ameliorates inflammatory pain by upregulating adenosine A3 receptor in complete Freund's adjuvant-induced arthritis rats

Manual acupuncture ameliorates inflammatory pain by upregulating adenosine A3 receptor in complete Freund's adjuvant-induced arthritis rats

  • Int Immunopharmacol. 2024 May 30:133:112095. doi: 10.1016/j.intimp.2024.112095.
Jing-Ping Xu 1 Qian-Wen Ouyang 2 Mei-Juan Shao 3 Hong Ke 1 Hong Du 3 Shang-Cheng Xu 3 Qian Yang 3 Yan-Ru Cui 4 Fei Qu 5
Affiliations

Affiliations

  • 1 Department of Physiology, Jiangxi University of Chinese Medicine, Nanchang, Jiangxi 330004, China.
  • 2 Nanchang People's Hospital, Jiangxi Province Key Laboratory for Breast Diseases, Nanchang, Jiangxi 334000, China.
  • 3 Department of Pharmacology, Jiangxi University of Chinese Medicine, Nanchang, Jiangxi 330004, China.
  • 4 Department of Physiology, Jiangxi University of Chinese Medicine, Nanchang, Jiangxi 330004, China. Electronic address: 20070943@jxutcm.edu.cn.
  • 5 Department of Pharmacology, Jiangxi University of Chinese Medicine, Nanchang, Jiangxi 330004, China. Electronic address: fei.qu@jxutcm.edu.cn.
Abstract

Background: Adenosine A3 receptor (A3R) exerts analgesic, anti-inflammatory, and anti-nociceptive effects. In this study, we determined the analgesic mechanism of manual acupuncture (MA) in rats with complete Freund's Adjuvant (CFA)-induced arthritis and explored whether MA ameliorates inflammation in these rats by upregulating A3R.

Methods: Sixty Sprague Dawley (SD) rats were randomly divided into the following groups: Control, CFA, CFA + MA, CFA + sham MA, CFA + MA + DMSO, CFA + MA + IB-MECA, and CFA + MA + Reversine groups. The arthritis rat model was induced by injecting CFA into the left ankle joints. Thereafter, the rats were subjected to MA (ST36 acupoint) for 3 days. The clinical indicators paw withdrawal latency (PWL), paw withdrawal threshold (PWT), and open field test (OFT) were used to determine the analgesic effect of MA. In addition, to explore the effect of A3R on inflammation after subjecting arthritis rats to MA, IB-MECA (A3R agonist) and Reversine (A3R antagonist) were injected into ST36 before MA.

Results: MA ameliorated the pathological symptoms of CFA-induced arthritis, including the pain indicators PWL and PWT, number of rearing, total ambulatory distance, and activity trajectory. Furthermore, after MA, the mRNA and protein expression of A3R was upregulated in CFA-induced arthritis rats. In contrast, the protein levels of TNF-α, IL-1β, Rap1, and p-p65 were downregulated after MA. Interestingly, the A3R agonist and antagonist further downregulated and upregulated inflammatory cytokine expression, respectively, after MA. Furthermore, the A3R antagonist increased the degree of ankle swelling after MA.

Conclusion: MA can alleviate inflammatory pain by inhibiting the NF-κB signaling pathway via upregulating A3R expression of the superficial fascia of the ST36 acupoint site in CFA-induced arthritis rats.

Keywords

Adenosine A(3) receptor; Analgesic; CFA-induced arthritis; Manual acupuncture; NF-κB.

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