Long-lasting desensitization of bladder afferents following intravesical resiniferatoxin and capsaicin in the rat.
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 mumol) 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 microgram/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).(ABSTRACT TRUNCATED AT 250 WORDS)
Craft
R M
RM
Department of Pharmacology, University of Arizona Health Sciences Center, Tucson, AZ 85724 USA Department of Pathology and Microbiology, University of Nebraska Medical Center, Omaha, NE 68198 USA.
Cohen
S M
SM
Porreca
F
F
D000283:Administration, Intravesical; D000344:Afferent Pathways / Q000187:drug effects; D000818:Animals; D002211:Capsaicin / Q000633:toxicity*; D003315:Cornea / Q000294:innervation; D003556:Cystitis / Q000139:chemically induced*; D004224:Diterpenes / Q000633:toxicity*; D005069:Evaluation Studies as Topic; D005260:Female; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors; D001743:Urinary Bladder / Q000294:innervation*; D015430:Weight Gain / Q000187:drug effects
D004224:Diterpenes; C024353:resiniferatoxin; D002211:Capsaicin