Sacral Nerve Stimulation Ameliorates Visceral Hypersensitivity Following 2,4,6-Trinitrobenzene Sulfonic Acid-Induced Colitis in Rats by Suppressing Inflammation and Reducing Colonic Epithelial Permeability.

OBJECTIVES

Visceral pain is a common and debilitating symptom of bowel disorders, such as irritable bowel syndrome and inflammatory bowel disease (IBD). Sacral nerve stimulation (SNS), widely used for fecal incontinence, has shown promise in treating inflammation and visceral hypersensitivity in rodent models, although its efficacy in IBD-associated visceral pain remains unclear. This study evaluated the effectiveness and underlying mechanisms of SNS on visceral hypersensitivity in a rodent IBD model.

MATERIALS AND

METHODS

Visceral hypersensitivity was induced through intracolonic administration of 2,4,6-trinitrobenzene sulfonic acid (TNBS). Rats received SNS or sham treatment (one h/d for ten days) beginning five days post-TNBS. SNS was applied using a set of parameters previously shown effective in treating visceral pain in other methods of neuromodulation.

RESULTS

Daily disease activity index scores increased significantly after TNBS but improved with SNS (p < 0.05). Tumor necrosis factor α levels in the distal colon rose in TNBS rats (55.2 pg/mg vs 37.5 pg/mg in saline, p = 0.004) and decreased with SNS (43.2 pg/mg, p = 0.025 vs sham). Visceral motor reflex (VMR) responses to colorectal distension (40-80 mm Hg) were elevated three- to fourfold in TNBS rats, which was reduced by 34%-73% with SNS (p < 0.001). Colitis reduced transepithelial electrical resistance (TEER, reflecting colonic epithelial permeability) by 48% (18.3 Ω·cm2), which improved by SNS (26.0 Ω·cm2, p = 0.035). Plasma lipopolysaccharide levels were elevated in TNBS-sham rats (0.72 EU/mL vs 0.20 EU/mL saline, p < 0.001) and reduced with SNS (0.45 EU/mL, p = 0.042). TEER negatively correlated with VMR responses.

CONCLUSIONS

SNS attenuates TNBS-induced visceral hypersensitivity by reducing inflammation and enhancing epithelial barrier integrity.