Ginger Moxibustion Activates TRPV1 to Modulate the Locus Coeruleus-Spinal Cord-Uterus Pathway and Alleviates Primary Dysmenorrhea in Rats

Abstract

Objective: To investigate the effect of ginger moxibustion at “Shenque” (CV8) and “Guanyuan” (CV4) acupoints on primary dysmenorrhea (PD) rats and explore the possible anti-inflammatory and analgesic mechanism. Methods: Forty female Sprague-Dawley (SD) rats were randomly divided into five groups: blank group (BG), model group (MG), ginger moxibustion group (GMG), antagonist capsazepine group (CPZG), and ibuprofen group (IG). PD models were established via cold stimulation combined with estradiol benzoate and oxytocin administration. GMG received ginger moxibustion, CPZG was pretreated with CPZ before ginger moxibustion, and IG received ibuprofen via gavage. Post-intervention, rat pain thresholds and writhing scores were measured; uterine pathology was observed via HE staining; Enzyme-linked immunosorbent assay (ELISA), immunohistochemistry (IHC), immunofluorescence (IF), and Western blotting (WB) were used to measure relevant biomarkers. Results: Ginger moxibustion significantly elevated pain thresholds and reduced writhing scores (vs MG, P<0.01). Capsazepine partially reversed these effects (vs GMG, P<0.05). Ginger moxibustion up-regulated TRPV1 and SP expression at acupoints (vs MG, P<0.01), whereas capsazepine suppressed their expression (vs GMG, P<0.01). Ginger moxibustion decreased uterine NE levels while increasing NE concentrations in both the spinal cord and locus coeruleus (vs MG, P<0.01); Following CPZ antagonism, uterine NE increased while central NE decreased (vs GMG, P <0.05). Ginger moxibustion downregulated serum TNF-α, IL-6 and uterine PGF2α (vs MG, P <0.01), while upregulating β2-AR expression; It promoted M2-type polarization of macrophages (increased CD206 and M2/M0 ratio, decreased CD86 and M1/M0 ratio, P <0.01), with CPZ partially reversing this effect. Conclusion: Ginger moxibustion at “Shenque” (CV8) and “Guanyuan” (CV4) acupoints exerts synergistic analgesic and anti-inflammatory effects by activating the TRPV1 channels in acupoint areas, initiating the bidirectional regulation of the locus coeruleus-spinal cord-uterus norepinephrine (NE) pathway, and inducing M2 polarization of macrophages.