2. Academic Validation
  3. Inhibition of P2X7 receptor in satellite glial cells contributes to electroacupuncture's analgesia in rats with CFA-induced inflammatory pain

Inhibition of P2X7 receptor in satellite glial cells contributes to electroacupuncture's analgesia in rats with CFA-induced inflammatory pain

  • Chin Med. 2025 Oct 5;20(1):159. doi: 10.1186/s13020-025-01227-6.
Yuxin Wu # 1,  Minghui Wu # 1,  Shuxin Tian # 1,  Zhengyi Lyu 1,  Bei Zhao 1,  Boxi Zheng 1,  Junying Du 1,  Junfan Fang 1,  Xiaofen He 1,  Boyi Liu 1,  Xiaomei Shao 1,  Jianqiao Fang 1,  Yi Liang 2
Affiliations

Affiliations

  • 1 Department of Neurobiology and Acupuncture Research, Key Laboratory of Acupuncture and Neurology of Zhejiang Province, The Third Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou, 310053, China.
  • 2 Department of Neurobiology and Acupuncture Research, Key Laboratory of Acupuncture and Neurology of Zhejiang Province, The Third Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou, 310053, China. liangyiwww@126.com.
  • # Contributed equally.
PMID: 41046250 DOI: 10.1186/s13020-025-01227-6
Abstract

Background: Accumulating evidence highlights the anti-inflammatory and analgesic effects of electroacupuncture (EA), yet the underlying mechanisms remain poorly understood. The P2X7 purinergic receptor (P2X7R), located in the peripheral and central nervous systems, has been implicated in the development of chronic inflammatory pain. Inhibition of P2X7R expression has been associated with the analgesic effects of EA. Within the dorsal root ganglia, P2X7R is exclusively expressed in satellite glial cells (SGCs), but its role in the anti-inflammatory effects of EA remains to be elucidated.

Methods: A chronic inflammatory pain model was established in rats via intraplantar injection of Complete Freund's Adjuvant (CFA). Western blotting, immunostaining, behavioral assay, pharmacological interventions, AAV-mediated knockdown assays, SGCs culture and real-time cell proliferation analysis were utilized to investigate the cellular mechanisms underlying the effects of EA at the ST36 and BL60 acupuncture points in mitigating inflammatory pain.

Results: Rats injected with CFA exhibited long-lasting pain hypersensitivity in the ipsilateral hind paw, accompanied by upregulated expression of P2X7R and TNF-α in the L4-6 DRGs. Pharmacological inhibition or shRNA-mediated knockdown of P2X7R in SGCs significantly attenuated inflammatory pain hypersensitivity, reduced p38 MAPK phosphorylation, and decreased TNF-α levels. EA treatment significantly alleviated CFA-induced pain hypersensitivity and suppressed P2X7R expression alongside its downstream p38 MAPK/TNF-α signaling. The analgesic effects of EA were reversed by the P2X7R agonist BzATP. In vitro findings confirmed that TNF-α secretion by SGCs was markedly elevated in the CFA model but reduced by EA treatment, mimicking the effects of P2X7R antagonism.

Conclusions: These findings demonstrate that the inhibition of P2X7R in SGCs and its downstream p38 MAPK/TNF-α signaling pathway contributes to the analgesic effects of EA in chronic inflammatory pain. Targeting peripheral P2X7R in SGCs may provide new insights into the cellular mechanisms of EA's anti-inflammatory effects.

Keywords

Electroacupuncture analgesia; Inflammatory pain; P2X7 purinergic receptor; P38 MAPK/TNF-α signaling; Satellite glial cell.

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