Activation of DMV cholinergic neurons mediates the anti-inflammatory effects of electroacupuncture in knee osteoarthritis mice

Background Knee osteoarthritis (KOA) is a leading cause of chronic disability in the elderly population. Although electroacupuncture (EA) has shown promising anti-inflammatory effects, the central neural mechanisms underlying its therapeutic efficacy remain incompletely elucidated. Methods A mouse model of KOA was established and treated with EA at the Zusanli (ST36) acupoint. Chemogenetic manipulation and fiber photometry recording were used to investigate the role of choline acetyltransferase (ChAT)-positive neurons in the dorsal motor nucleus of the vagus (DMV). Knee joint tissues were collected for histopathological evaluation using hematoxylin and eosin staining, Safranin O/Fast Green staining, and collagen II immunohistochemistry. Synovial levels of inflammatory cytokines (TNF-α, IL-1β, and IL-6) and dopamine (DA) were quantified by enzyme-linked immunosorbent assay (ELISA). Results EA at ST36 significantly alleviated cartilage damage and suppressed the upregulation of inflammatory cytokines in KOA mice. The DMV was identified as a key brain region responsive to EA stimulation, and activation of EA-responsive DMV neurons reproduced the therapeutic effects of EA. Furthermore, EA-responsive DMV neurons were found to be predominantly ChAT-positive, and chemogenetic inhibition of DMV ChAT neurons abolished the anti-inflammatory effects of EA in KOA mice. Mechanistically, both EA treatment and activation of DMV ChAT neurons were associated with increased DA release into the synovial tissue. Conclusions Our findings identify a central neural mechanism underlying the therapeutic effects of EA in KOA. Specifically, EA at ST36 activates DMV ChAT neurons, which subsequently promote adrenal DA release, thereby inhibiting inflammatory cytokine production in the knee joint and alleviating KOA-associated inflammation. These findings provide novel insights into the central neural mechanisms through which EA exerts its therapeutic effects in KOA.