Intrathecal Oxytocin Inhibits Visceromotor Reflex and Spinal Neuronal Responses to Noxious Distention of the Rat Urinary Bladder

Abstract

Oxytocin (OXY) is a neuropeptide that has recently been recognized as an important component of descending analgesic systems. The present study sought to determine if OXY produces antinociception to noxious visceral stimulation. Urethane-anesthetized female rats had intrathecal catheters placed acutely, and the effect of intrathecal OXY on visceromotor reflexes (VMRs; abdominal muscular contractions quantified using electromyograms) to urinary bladder distension (UBD; 10-60 mm Hg, 20 seconds; transurethral intravesical catheter) was determined. The effect of OXY applied to the surface of exposed spinal cord was determined in lumbosacral dorsal horn neurons excited by UBD using extracellular recordings. Oxytocin doses of 0.15 or 1.5 μg inhibited VMRs to UBD by 37% ± 8% and 68% ± 10%, respectively. Peak inhibition occurred within 30 minutes and was sustained for at least 60 minutes. The effect of OXY was both reversed and prevented by the intrathecal administration of an OXY-receptor antagonist. Application of 0.5 mM OXY to the dorsum of the spinal cord inhibited UBD-evoked action potentials by 76% ± 12%. Consistent with the VMR studies, peak inhibition occurred within 30 minutes and was sustained for greater than 60 minutes. These results argue that intrathecal OXY produces an OXY receptor-specific antinociception to noxious UBD, with part of this effect due to inhibition of spinal dorsal horn neurons. To our knowledge, these studies provide the first evidence that intrathecal OXY may be an effective pharmacological treatment for visceral pain.