Strain-Dependent Effect of Imipramine on Responses of Mechanosensitive Pelvic Nerve Afferent Fibers to Bladder Distension

Abstract

Background: This study evaluated the effect of imipramine, which inhibits colonic afferents, on responses of the peripheral afferent nerve innervating bladder to noxious urinary bladder distension in different strains of rats [Sprague-Dawley, spontaneously hypertensive rat (SHR) and normotensive Wistar-Kyoto (WKY)]. Methods: Rats were anesthetized with sodium pentobarbital and single-afferent nerve fibers in the L6 dorsal root were teased for recording the inhibitory response to urinary bladder distension (60 mmHg, 30s) following intravenous injection of accumulative doses of imipramine. Results: The stimulus-response functions of mechanosensitive afferent nerves were not enhanced in SHR. Intravenous injection of imipramine significantly reduced responses of mechanosensitive afferent nerves to urinary bladder distension, on all afferent fibers. Interestingly imipramine showed strain-dependent suppressions on afferent fibers, with strong suppression in SHR (ID50 2.96 mg/kg) and weak in WKY (10 mg/kg, to 6 ± 7% of control in SHR vs. 72 ± 9% of control in WKY). Conclusion: The effects of imipramine in bladder dysfunction/pain are likely due to direct actions on afferent fibers. The enhanced inhibitory effect of imipramine in the SHR suggests that a different mechanical encoding mechanism is involved in the regulation of bladder afferent nerve activity in SHR.