Electroacupuncture Alleviates KOA-Induced Pain and Cartilage Degeneration via NGF/TrkA Pathway

Introduction: Knee osteoarthritis (KOA) is a chronic degenerative joint disease marked by pain, cartilage degradation, and limited mobility. Existing treatments remain suboptimal due to limited efficacy and adverse effects, highlighting the urgent need for safer, mechanism-based therapies. Electroacupuncture (EA) has demonstrated clinical benefits in KOA, yet its underlying molecular mechanisms remain unclear. Methods: A KOA rat model was established via intra-articular injection of monosodium iodoacetate (MIA). EA was applied at Dubi (ST35) and Neixiyan (EX-LE5) acupoints. We assessed the effect of EA on nociceptive behavior in rats with KOA using von Frey filament testing, weight-bearing asymmetry measurements, and spontaneous pain assays. Cartilage degeneration was analyzed via toluidine blue staining, while immunofluorescence staining quantified protein expression levels in cartilage and dorsal root ganglia (DRG). Inhibitor and agonist injections were employed to evaluate the specific involvement of the NGF/TrkA pathway in EA-mediated effects. Results: EA significantly reduced mechanical allodynia ( p < 0.001), weight-bearing asymmetry ( p < 0.001), spontaneous pain ( p < 0.001). EA decreased macroscopic chondropathy score ( p < 0.01) and cartilage degeneration score ( p < 0.001). EA inhibited MMP13 expression ( p < 0.05), suppressed NGF ( p < 0.001) and TrkA ( p < 0.05) expression, decreased PGP9.5 overexpression ( p < 0.05), and downregulated pro-inflammatory cytokines IL-1β ( p < 0.01) and TNF-α ( p < 0.01). Pharmacological inhibition of NGF/TrkA mimicked EA’s effects, while activation of this pathway counteracted its analgesia. EA selectively downregulated TrkA in CGRP + ( p < 0.01), but not IB4 + ( p > 0.05) or NF200 + ( p > 0.05) DRG neurons subtypes. Conclusion: Our results demonstrate that EA alleviates KOA, possibly via inhibiting NGF/TrkA pathway activation in knee joints and reducing TrkA expression in CGRP + sensory neurons, supporting the therapeutic potential of EA for KOA. Keywords: osteoarthritis, electroacupuncture, nerve growth factor, pain, cartilage diseases