LONG-LASTING DESENSITIZATION OF BLADDER AFFERENTS FOLLOWING INTRAVESICAL RESINIFERATOXIN AND CAPSAICIN IN THE RAT

The present study was conducted to determine whether long-lasting dese nsitization of bladder afferents could be achieved using a single loca l application of the capsaicin (CAP)-like irritant resiniferatoxin (RT X), and to compare the effects of RTX and CAP on behavioral and histol ogical endpoints. While rats were anesthetized, vehicle (VEH),RTX (10- 100 nmol) or CAP (10-100 mu mol) was instilled in the bladder (intrave sical, i.ves.) via a cannula surgically implanted into the bladder dom e. Beginning 1 week after treatment, once per week for 4 weeks, rats w ere tested behaviorally for desensitization to i.ves. RTX (10 nmol) us ing 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 o r CAP were more completely desensitized at week 1, and desensitization did not diminish by week 4. Separate groups of rats tested 8 weeks af ter treatment showed substantial recovery. Rats pretreated with RTX bu t tested only with VEH for the first 3 weeks showed desensitization at week 4 approximately equivalent to that of RTX-treated rats tested wi th RTX every week. Sensitivity of corneal afferents to RTX (1.0 mu g/m l) at week 4 was not different between VEH- and RTX- or CAP-treated ra ts. Gross and histological examination of bladder tissue indicated tha t both RTX and CAP produced inflammation, which diminished in a dose- and time-dependent manner (1-8 weeks post-treatment). The present stud y demonstrates that a single, local exposure to RTX produces desensiti zation of bladder afferents that lasts approximately 2 months, and tha t intervening exposures to a 10-fold lower dose do not significantly e nhance desensitization. RTX is approximately 1000 times more potent th an CAP in producing desensitization in this behavioral model, but only 100-300 times more potent in producing tissue inflammation, suggestin g that RTX may be superior to CAP as a desensitization therapy.