Oxytocin relieves visceral hypersensitivity through GABAB1-TRPV1 in rats with irritable bowel syndrome.

Oxytocin has been found to modulate and improve pain in humans, but the mechanisms underlying these antinociceptive properties, especially in visceral hypersensitivity, are still unclear. Irritable bowel syndrome (IBS) models were established by colorectal distention in newborn rats aged 8 to 14 days, and visceral hypersensitivity was assessed using electromyogram (EMG). Oxytocin or saclofen was administered intrathecally to evaluate visceral hypersensitivity in the rats. The protein expressions of oxytocin receptor (OTR), γ-aminobutyric acid type B1 receptor (GABAB1), and transient receptor potential vanilloid 1 (TRPV1) in the lumbosacral spinal cord regions were measured. IBS rats exhibited a unique spinal cord molecular signature comprising decreased OTR/GABAB1 and increased TRPV1 expression. Intrathecal oxytocin treatment not only normalized these molecular alterations (increasing GABAB1 while decreasing TRPV1) but also ameliorated visceral pain behaviors. Crucially, this therapeutic effect was fully reversed by GABAB1 inhibition, establishing the necessity of intact GABAergic signaling for oxytocin-mediated analgesia. Collectively, these findings indicate that oxytocin relieves visceral hypersensitivity through the regulation of GABAB1 and TRPV1 in the spinal cord of IBS rats.