Long-lasting desensitization of bladder afferents following intravesical resiniferatoxin and capsaicin in the rat

Abstract

The present study was conducted to determine whether long-lasting desensitization of bladder afferents could be achieved using a single local application of the capsaicin (CAP)-like irritant resiniferatoxin (RTX), and to compare the effects of RTX and CAP on behavioral and histological endpoints. While rats were anesthetized, vehicle (VEH), RTX (10–100 nmol) or CAP (10–100 μmol) was instilled in the bladder (intravesical, i.ves.) via a cannula surgically implanted into the bladder dome. Beginning 1 week after treatment, once per week for 4 weeks, rats were tested behaviorally for desensitization to i.ves. RTX (10 nmol) using the abdominal lick test. Rats pretreated with low doses of RTX and CAP were partially desensitized at week 1; desensitization diminished over weeks 2–3. In contrast, rats pretreated with high doses of RTX or CAP were more completely desensitized at week 1, and desensitization did not diminish by week 4. Separate groups of rats tested 8 weeks after treatment showed substantial recovery. Rats pretreated with RTX but tested only with VEH for the first 3 weeks showed desensitization at week 4 approximately equivalent to that of RTX-treated rats tested with RTX every week. Sensitivity of corneal afferents to RTX (1.0 μg/ml) at week 4 was not different between VEH- and RTX- or CAP-treated rats. Gross and histological examination of bladder tissue indicated that both RTX and CAP produced inflammation, which diminished in a dose- and time-dependent manner (1–8 weeks post-treatment). The present study demonstrates that a single, local exposure to RTX produces desensitization of bladder afferents that lasts approximately 2 months, and that intervening exposures to a 10-fold lower dose do not significantly enhance desensitization. RTX is approximately 1000 times more potent than CAP in producing desensitization in this behavioral model, but only 100–300 times more potent in producing tissue inflammation, suggesting that RTX may be superior to CAP as a desensitization therapy.