TEMPORAL PARAMETERS OF DESENSITIZATION TO INTRAVESICAL RESINIFERATOXIN IN THE RAT

Temporal factors affecting desensitization of bladder sensory afferent s to the capsaicin-like irritant resiniferatoxin (RTX) were studied, t o determine optimal treatment parameters for clinical application of s uch substances. Four days after implantation of a chronic cannula into the bladder dome, vehicle or RTX (0.1-10 nmol) was injected into the bladders of awake, freely moving rats four times at 60-min intervals f or exposure durations of 5, 15, or 45 min, or at intervals of 15, 60, os 120 min (duration 5 min). The first RTX injection dose-dependently increased time spent engaged in abdominal licking. Regardless of expos ure interval and duration, time spent licking increased to a lesser ex tent with each subsequent injection, indicating desensitization of sen sory afferents. Magnitude and duration of desensitization were dose de pendent for all exposure regimens, and there were few differences betw een groups. Desensitization at 24 h was also greater in rats exposed f our times compared to rats exposed once. Following four exposures to R TX, nearly complete recovery occurred within 7-14 days, in a dose-depe ndent manner. Thus, magnitude and duration of desensitization to local ly administered RTX depend primarily on dose and number of exposures t o RTX; duration of exposure and interval between exposures within the ranges studied were less important determinants.