Serotonergic and noradrenergic facilitation of the visceromotor reflex evoked by urinary bladder distension in rats with inflamed bladders

Abstract

Bladder inflammation resulting from intravesical administration of zymosan significantly enhances the visceromotor reflex (VMR) evoked by urinary bladder distension (UBD). The present study examined whether intrathecal (i.t.) administration of receptor antagonists to either norepinephrine (NE) or serotonin (5-HT) altered this enhancement effect. I.t. administration of the non-specific 5-HT receptor antagonist methysergide (30 microg), the 5-HT(3) receptor antagonist ondansetron, or the 5-HT(1A) receptor antagonist WAY 100635 eliminated the enhancement effect produced by intravesical zymosan and also tended to reduce electromyographic (EMG) responses to UBD in non-inflamed rats. I.t. administration of either the non-specific NE receptor antagonist phentolamine (30 microg) or the alpha(1) antagonist WB 4101 also eliminated the enhancement effect, whereas i.t. administration of the alpha(2) antagonist yohimbine failed to significantly affect the enhancement effect. The effects of phentolamine and methysergide were not mediated by changes in bladder compliance. This is the first study to demonstrate that bladder hypersensitivity resulting from bladder inflammation is partly mediated by 5-HT and NE facilitatory effects. Based on these and previous findings we conclude that the net nociceptive response to bladder distension under conditions of bladder inflammation represents a complex interaction of facilitatory influences of spinal 5-HT and NE, and inhibitory influences of spinal opioids.