Electroacupuncture Improves Nitroglycerin-Induced Generalized Hypersensitivity Associated with a Migraine-Like State...

To investigate whether electroacupuncture (EA) alleviates generalized hypersensitivity associated with a nitroglycerin (NTG)-induced migraine-like state in rats and to identify EA-associated molecular changes in the trigeminal ganglion (TG), focusing on the CXCL13/CXCR5 axis.

Male Sprague-Dawley rats were randomly assigned to control, model, EA, and sham EA groups (n = 8/group). Except for the control group, rats received NTG (10 mg/kg, intraperitoneally) on days 1, 3, 5, 7, and 9. EA was applied daily at GB20 and GB34, while sham EA was applied at non-acupoints. Mechanical paw withdrawal threshold and thermal paw withdrawal latency were assessed at baseline and 2 h after each injection. Plasma calcitonin gene-related peptide (CGRP) was measured by ELISA. TG RNA sequencing was performed in the control, model, and EA groups (n = 3/group), followed by GO/KEGG analysis, qPCR, and immunofluorescence validation.

EA significantly increased mechanical paw withdrawal threshold and thermal paw withdrawal latency in NTG-treated rats. On day 9, both measures were higher in the EA group than in the model group (both adjusted P < 0.0001), whereas sham EA produced no significant improvement. Plasma CGRP was lower in the EA group than in the model group (adjusted P = 0.0155). Exploratory RNA sequencing identified inflammation-, immune-, and chemokine-related TG changes. qPCR showed lower Cxcl13 and Cxcr5 expression in the EA group than in the model group (adjusted P = 0.0242 and 0.0009, respectively). Immunofluorescence showed consistent reductions in CXCL13 and CXCR5 mean fluorescence intensity (adjusted P = 0.0115 and 0.0020, respectively).

EA attenuated NTG-induced generalized hypersensitivity and reduced plasma CGRP levels, accompanied by decreased CXCL13/CXCR5 expression in the TG. Whether TG CXCL13/CXCR5 downregulation contributes causally to these effects remains to be determined.