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Journal of Traditional Chinese Medicine >

2026 , Vol. 46 >Issue 1: 85 - 94

DOI: https://doi.org/10.19852/j.cnki.jtcm.2026.01.008

Original Articles

Alleviation of nitroglycerin-induced migraine in rats: inhibition of central sensitization by optimizing Qinggan Jieyu decoction (清肝解郁方) via regulation of purinergic receptor P2X ligand-gated ion channel 7 and autophagy

  • Jiazheng LI ,
  • Bo ZHOU
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  • Department of Neurology, Xiyuan Hospital of China Academy of Chinese Medical Sciences, Beijing 100091, China

Received date: 2024-11-13

  Accepted date: 2025-05-19

  Online published: 2026-01-28

Supported by

China Academy of Chinese Medical Sciences Innovation Fund:Multicenter Randomized Controlled Study on the Intervention of Yiqi Huoxue Huatan Tongluo decoction in Post-Stent Restenosis of Vertebral Arteries(CI2021A01308);In-Hospital Mentorship Program of Xiyuan Hospital, China Academy of Chinese Medical Sciences-Zhou Shaohua(0203055)

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Abstract

OBJECTIVE: To investigate the effects of optimizing Qinggan Jieyu decoction (清肝解郁方) on purinergic receptor P2X ligand-gated ion channel 7 (P2X7R) and autophagy in migraine model rats based on molecular biology and histopathology.

METHODS: A migraine rat model was established by a single subcutaneous nitroglycerin (NTG) injection into the posterior neck. QGJY was administered via gavage for 7 d prior to NTG induction. Behavioral changes, central sensitization biomarkers, and inflammatory cytokine levels were analyzed to evaluate migraine severity. Western blot, immunofluorescence, quantitative real-time PCR, and transmission electron microscopy were employed to assess P2X7R expression and autophagy activity in trigeminal nucleus caudalis (TNC) tissues. The P2X7R agonist 2’ (3’)-O-(4-Benzoylbenzoyl) adenosine-5’-triphosphate (BzATP) was further utilized to validate QGJY's regulatory effects.

RESULTS: QGJY significantly reduced cage-climbing and head-scratching frequencies in NTG-induced migraine rats, downregulated serum and TNC levels of interleukin-1 beta, interleukin-6, and tumor necrosis factor-alpha, and suppressed central sensitization markers (substance P; calcitonin gene-related peptide; and c-fos induced growth factor) in TNC tissues (P < 0.05). QGJY markedly decreased microglial cell counts and average immunofluorescence intensity in TNC tissues and promoted elongation of microglial protrusions (P < 0.05). Concurrently, QGJY downregulated P2X7R protein and mRNA expression, reduced the light chain 3 (LC3)-II/LC3-I ratio, elevated ubiquitin-binding protein p62 levels, and diminished autophagosome numbers in TNC tissues (P < 0.05). Furthermore, QGJY reversed BzATP-induced P2X7R upregulation (P < 0.05).

CONCLUSIONS: QGJY alleviates migraine and inhibits central sensitization in rats, potentially by downregulating P2X7R expression, concomitantly suppressing autophagy, attenuating microglial activation, and reducing pro-inflammatory cytokine release.

Key words： migraine disorders; receptors, purinergic P2X7; autophagy; optimizing Qinggan Jieyu decoction

Cite this article

Jiazheng LI , Bo ZHOU . Alleviation of nitroglycerin-induced migraine in rats: inhibition of central sensitization by optimizing Qinggan Jieyu decoction (清肝解郁方) via regulation of purinergic receptor P2X ligand-gated ion channel 7 and autophagy[J]. Journal of Traditional Chinese Medicine, 2026 , 46(1) : 85 -94 . DOI: 10.19852/j.cnki.jtcm.2026.01.008

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