TY - JOUR
T1 - Electroacupuncture alleviates central post-stroke pain in rats by modulating miR-21-5p/TGF-β/Smads pathway
AU - Tian, Guihua
AU - Wu, Yang
AU - Shang, Zhihao
AU - An, Nan
AU - Hao, Huifeng
AU - He, Ke
AU - Su, Youxiang
AU - Yang, Luyu
AU - Wang, Meiyue
AU - Li, Xinyi
N1 - Publisher Copyright:
© The Author(s) 2025.
PY - 2026/12
Y1 - 2026/12
N2 - Background: Central post-stroke pain (CPSP) poses a persistent challenge with limited responses to current pharmacological interventions. Recent evidence implicates miR-21 and its downstream TGF-β/Smads signaling pathway in pain pathophysiology. This study investigates whether the analgesic effect of electroacupuncture (EA) is related to miR-21/TGF-β/Smads signaling pathway in CPSP. Methods: CPSP was induced in rats by collagenase-IV injection into the right thalamic ventral posterolateral nucleus to produce a focal hemorrhagic stroke lesion. miR-21-5p and Smad7 expressions were manipulated by adenoviral transfection. Pain thresholds were assessed during 15 days after CPSP induction, followed by brain tissue analysis using nissl staining, immunofluorescence, immunohistochemistry, and molecular assays. A dual-luciferase reporter assay was employed to verify the direct binding interaction between miR-21-5p and Smad7. Results: The results showed EA significantly alleviated CPSP, and meanwhile, downregulated miR-21-5p, upregulated Smad7, and reduced TGF-β1, p-Smad2, and p-Smad3 expressions, glial hyperactivation and inflammatory factors (IL-1β, IL-6, TNF-α) in CPSP rats. In addition, miR-21-5p inhibition resulted in analgesic effect, while miR-21-5p overexpression or Smad7 inhibition counteracted the effect of EA. Conclusions: These results indicate that the mechanisms underlying EA-induced analgesia involve downregulating miR-21-5p, consequently inhibiting neuroinflammation by regulating Smad7/TGF-β/Smads signaling pathway, providing a novel insight for probing the molecular mechanism of analgesic effect of EA.
AB - Background: Central post-stroke pain (CPSP) poses a persistent challenge with limited responses to current pharmacological interventions. Recent evidence implicates miR-21 and its downstream TGF-β/Smads signaling pathway in pain pathophysiology. This study investigates whether the analgesic effect of electroacupuncture (EA) is related to miR-21/TGF-β/Smads signaling pathway in CPSP. Methods: CPSP was induced in rats by collagenase-IV injection into the right thalamic ventral posterolateral nucleus to produce a focal hemorrhagic stroke lesion. miR-21-5p and Smad7 expressions were manipulated by adenoviral transfection. Pain thresholds were assessed during 15 days after CPSP induction, followed by brain tissue analysis using nissl staining, immunofluorescence, immunohistochemistry, and molecular assays. A dual-luciferase reporter assay was employed to verify the direct binding interaction between miR-21-5p and Smad7. Results: The results showed EA significantly alleviated CPSP, and meanwhile, downregulated miR-21-5p, upregulated Smad7, and reduced TGF-β1, p-Smad2, and p-Smad3 expressions, glial hyperactivation and inflammatory factors (IL-1β, IL-6, TNF-α) in CPSP rats. In addition, miR-21-5p inhibition resulted in analgesic effect, while miR-21-5p overexpression or Smad7 inhibition counteracted the effect of EA. Conclusions: These results indicate that the mechanisms underlying EA-induced analgesia involve downregulating miR-21-5p, consequently inhibiting neuroinflammation by regulating Smad7/TGF-β/Smads signaling pathway, providing a novel insight for probing the molecular mechanism of analgesic effect of EA.
KW - Central post-stroke pain
KW - Electroacupuncture
KW - Glial activation
KW - miR-21-5p
KW - Neuroinflammation
KW - Smad7
UR - https://www.scopus.com/pages/publications/105028446654
U2 - 10.1186/s10194-025-02247-1
DO - 10.1186/s10194-025-02247-1
M3 - Article
C2 - 41454256
AN - SCOPUS:105028446654
SN - 1129-2369
VL - 27
JO - Journal of Headache and Pain
JF - Journal of Headache and Pain
IS - 1
M1 - 23
ER -