Differential physiological responses to electroacupuncture at ST36 and SP6 in CFA-induced inflammatory arthritis: serum metabolomic evidence for acupoint-specific redox regulation

Electroacupuncture (EA) modulates neuroimmune and metabolic pathways, but acupoint-specific physiological responses remain poorly characterized. This study investigated acupoint-dependent differences in nociceptive behavior, synovial inflammation, and serum metabolomic profiles in rats with complete Freund's adjuvant (CFA)-induced knee arthritis. Animals were assigned to three groups: CFA without EA, CFA with EA at SP6, and CFA with EA at ST36. EA at ST36 significantly improved hindlimb weight-bearing (74.1% vs. 45.3% at post-injection day 8; p < 0.01), whereas EA at SP6 did not reach significance. Both acupoints comparably reduced synovial inflammation scores. Targeted GC-MS/MS serum metabolomics identified 14 significantly altered metabolites; 2-hydroxybutyric acid (2-HBA) showed the largest fold-change and was selectively normalized by EA at ST36. Intra-articular 2-HBA injection did not alter pain behavior, indicating it represents a systemic physiological consequence of inflammatory-metabolic burden rather than a nociceptive mediator. These findings demonstrate acupoint-specific modulation of redox-metabolic homeostasis by EA in inflammatory arthritis.