Effects of Intravesical Instillation of Resiniferatoxin on Bladder Function and Nociceptive Behavior in Freely Moving, Conscious Rats

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Abstract
A new animal model in which to concurrently evaluate bladder function and nociceptive behavior was developed using freely moving, noncatheterized, conscious rats to assess the nociceptive behavior responses induced by intravesical instillation of resiniferatoxin (Sigma) and its relationship with bladder dysfunction. In female Sprague-Dawley rats resiniferatoxin (0, 0.3 and 3 microM) was instilled via a catheter that was temporarily inserted into the bladder through the urethra. After removing the catheter the incidence of nociceptive behavior (lower abdominal licking and freezing) was scored. Voided urine was collected continuously to measure bladder capacity. In some rats the pudendal nerves were transected bilaterally to eliminate the activation of urethral afferents by resiniferatoxin. Intravesical instillation of resiniferatoxin induced decreased bladder capacity and increased nociceptive behaviors, such as licking and freezing, which were blocked by the transient receptor potential vanilloid receptor 1 antagonist BCTC (Biomol). In rats with pudendal nerve transection the early phase of resiniferatoxin induced licking was decreased without affecting the resiniferatoxin induced decrease in bladder capacity and late phase licking behavior. Resiniferatoxin induced late phase licking in the water unloaded group was observed to a lesser extent than in the water loaded diuresis group. The intravesical instillation of resiniferatoxin, which decreases bladder capacity, acts by at least 3 distinct mechanisms to induce licking behavior, including 1) an immediate response mediated by the activation of urethral afferents in the pudendal nerve, 2) a late response evoked by the direct stimulation of C-fiber afferents in the bladder and 3) gradual facilitation of the response elicited by the bladder wall distention induced by rapid bladder filling.

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