Sex-specific effects of chronic electrical acustimulation and sacral nerve stimulation in a rodent model of irritable bowel syndrome.

Irritable bowel syndrome (IBS) is characterized by visceral hypersensitivity, impaired epithelial barrier function, and autonomic dysregulation, and has a higher prevalence in women. Most preclinical studies rely primarily on male animals, limiting the translational relevance of these findings to the female population. To address this gap, we investigated the effects of chronic bilateral electrical acustimulation (BEA) at acupoint ST36 in male and female rats, and sacral nerve stimulation (SNS) in male rats using an IBS model induced by neonatal acetic acid irritation. Visceral sensitivity was assessed using electromyographic responses to colorectal distension, and barrier integrity was evaluated using transepithelial electrical resistance and tight junction protein expression. Circulating norepinephrine (NE) and pancreatic polypeptide (PP) levels were measured as autonomic biomarkers. Additionally, acetylcholine (ACh) release and tumor necrosis factor-alpha (TNF-α) levels were assessed to evaluate the activation of the cholinergic anti-inflammatory pathway. Both BEA and SNS significantly decreased visceral hypersensitivity and improved the barrier function. Dysregulation of NE and PP levels was normalized following treatment, with females showing greater PP modulation, suggesting sex-dependent autonomic responses. BEA and SNS also increased ACh release and reduced TNF-α levels. Together, our results highlight BEA as a non-invasive modality with therapeutic potential comparable to that of invasive SNS for managing IBS-associated visceral pain. PERSPECTIVE: BEA and SNS effectively reduced visceral hypersensitivity and restored intestinal barrier integrity in a preclinical model of IBS. These therapies normalize autonomic balance and, by activating the cholinergic anti-inflammatory pathway, suppress inflammation. Notably, BEA provides a non-invasive, clinically viable alternative to SNS with comparable therapeutic efficacy across sexes.