Electroacupuncture at ST25 ameliorated gastrointestinal dysmotility via downregulation sympathetic nerve-mediated α2-adrenoceptors in postoperative ileus

Postoperative ileus (POI) is a prevalent complication resulting from an imbalance in sympathetic activity or dysregulation of the intestinal immune system. Research has shown that interactions between the peripheral nervous system and immune system modulate intestinal functions. Electroacupuncture (EA) has been shown to ameliorate gastrointestinal dysmotility in patients with POI; however, the specific pathways and molecular mechanisms underlying its effects remain unclear. Here, we reported the signaling pathways that mediate the regulatory effects of EA in POI. Our findings indicated that EA ameliorated gastrointestinal dysmotility, inhibited celiac sympathetic overactivation, and reduced norepinephrine (NE) release. Notably, NE released by the sympathetic nerve terminals regulates the immune system primarily via its stimulation of α2-adrenoceptors (α2-ARs). α2-ARs could regulate macrophage activation in POI and were the key receptors for macrophages to perform neuroimmunomodulatory functions. Furthermore, sympathectomy and α2-ARs antagonist could mimic the improvement effects of EA on gastrointestinal motility and inflammatory response. Our findings demonstrated the pivotal function of the NE-α2-ARs signaling pathways in the modulation of POI, potentially contributing to the development of EA-based therapeutic interventions for gastrointestinal dysmotility disorders after surgery.NEW & NOTEWORTHY Electroacupuncture (EA) ameliorated gastrointestinal dysmotility and inhibited celiac sympathetic overactivation. The α2-adrenergic signaling pathway was involved in the regulation of gastrointestinal dysmotility and was regulated by EA stimulation. The α2-adrenoceptors (α2-ARs) regulated the activation of macrophages in postoperative ileus (POI). The improvement of EA in gastrointestinal motility was mimicked by sympathectomy and α2-adrenoceptors antagonist.