Synergistic Inhibition of Spinal TRPV1 Signaling by Combined Eye Acupuncture and Electroacupuncture Alleviates Inflammatory Pain in a Rat Model of Knee Osteoarthritis.

BACKGROUND

Chronic pain caused by knee osteoarthritis (KOA) remains inadequately managed by safe, non-pharmacological therapies. Although acupuncture is recommended for KOA pain by clinical guidelines, the efficacy of single-modality acupuncture remains modest, and the synergistic mechanisms of combining different acupuncture modalities are poorly understood.

OBJECTIVE

To determine whether combining eye acupuncture (EAp) with electroacupuncture (EA) produces greater analgesia in a rat KOA model via regulation of TRPV1 signaling in the spinal dorsal horn (SDH) and dorsal root ganglia (DRG).

METHODS

Thirty-six Sprague-Dawley rats (19 males, 17 females) were randomized into sham, model, EA, and combination (EA + EAp) groups (n = 9 per group, each containing 4-5 rats of each sex). KOA was induced by anterior cruciate ligament transection combined with medial meniscectomy. After 7 days of intervention, mechanical and thermal pain thresholds were assessed. Serum concentrations of PGE2, IL-1β, IL-6, and TNF-α were quantified by ELISA. TRPV1 expression in SDH and DRG was detected by immunofluorescence and Western blot.

RESULTS

Combination treatment significantly elevated pain thresholds and was associated with reduced levels of all four cytokines compared to the model and EA groups (P < 0.05 or P < 0.01). On day 7, the combination group showed a 2.2-fold increase in MWT compared to the model group (18.7 ± 2.6 g vs 8.5 ± 1.9 g, P < 0.001) and a 31.7% increase compared to the EA group (P < 0.01). Immunofluorescence showed the lowest TRPV1/DAPI fluorescence intensity ratio in the combination group in both DRG and SDH (P < 0.01 vs model; P < 0.05 vs EA). Western blot showed that combination therapy was associated with markedly lower total TRPV1 and phosphorylated TRPV1 (p-TRPV1) protein levels compared with the model and EA groups, with consistent trends in male and female rats.

CONCLUSION

Combined EAp and EA exert synergistic anti-inflammatory and analgesic effects in KOA rats, which are associated with downregulation of TRPV1 signaling in the SDH and DRG.