Published online Jun 7, 2025. doi: 10.3748/wjg.v31.i21.107395
Revised: April 11, 2025
Accepted: May 23, 2025
Published online: June 7, 2025
Processing time: 75 Days and 23.9 Hours
Diabetic gastroparesis (DGP), characterized by delayed gastric emptying and impaired motility, poses significant therapeutic challenges due to its complex neural and molecular pathophysiology. Emerging evidence suggests that electroa
To elucidate the neural mechanisms underlying EA at ST36 improving DGP gastric motility through the nucleus tractus solitarius (NTS)-vagal axis.
The DGP model was established via a single high-dose intraperitoneal injection of 2% streptozotocin combined with an 8-week high-sugar/high-fat diet. Interven
The study found that EA significantly increased the rate of gastric emptying, restored the slow-wave rhythms of the stomach, and improved the architecture of the smooth muscles in the stomach. This was evidenced by a reduction in inflammatory infiltration and an increase in the expression of nNOS, C-kit, and SCF. Mechanistically, EA activated vagal targets (ChAT and α7nAChR) at ST36, transmitting signals via spinal segments L4-L6 to the NTS, subsequently regulating gastrointestinal peptides (Gas, MLT, VIP) and restoring interstitial cells of Cajal (ICCs) function via subdiaphragmatic vagal efferent pathways. It is crucial to note that subdiaphragmatic vagotomy led to the abrogation of EA-induced enhancements in gastric motility and ICC recovery, thereby confirming the indispensable role of vagal efferent signalling.
EA provides a novel molecular mechanism for improving gastrointestinal motility in DGP via a peripheral stimulation (ST36), spinal afferent (L4-L6), brainstem integration (NTS), vagal efferent (gastric) circuit.
Core Tip: Multimodal validation: Electroacupuncture (EA) significantly enhanced gastric emptying (validated by positron emission tomography-computed tomography), restored gastric slow-wave rhythms, and improved smooth muscle architecture via upregulation of neuronal nitric oxide synthase, cluster of differentiation 117, stem cell factor. Mechanistic insight: EA activates cholinergic targets (choline acetyltransferas/α7 nicotinic acetylcholine receptor) at ST36, transmits signals via spinal L4-L6 afferents to the nucleus tractus solitarius, and modulates gastrointestinal peptides (ghrelin, motilin, vasoactive intestinal peptide) through subdiaphragmatic vagal efferent, ultimately restoring interstitial cells of Cajal function. Translational relevance: Subdiaphragmatic vagotomy abolished EA’s therapeutic effects, unequivocally establishing vagal efferent signaling as indispensable.