TETRACAINE ATTENUATES IRRITANCY WITHOUT ATTENUATING DESENSITIZATION PRODUCED BY INTRAVESICAL RESINIFERATOXIN IN THE RAT

The irritancy of initial application of capsaicin and related substanc es limits their therapeutic potential as novel analgesics. The purpose of the present study was to determine whether the irritant properties of the potent, capsaicin-like compound resiniferatoxin (RTX) would be attenuated by pretreatment with a local anesthetic and to determine w hether the local anesthetic had significant effects on RTX-induced des ensitization of sensory afferents. A model of visceral nociception in which irritants are instilled directly into the bladder (intravesical, i.ves.) of awake, freely moving rats was used. The nociceptive respon se, abdominal licking (grooming) was scored for 15 min; locomotor acti vity was scored concurrently. Tetracaine (0.125-1.0%) attenuated the i ncreases in abdominal licking produced by RTX (3.0 nmol) in a dose- an d time-dependent manner. At high doses, tetracaine also suppressed loc omotor activity. Thirty minutes and 24 h later, the same dose of RTX w as administered again to assess development of desensitization of blad der sensory afferents. Rats that had been pretreated with saline showe d decreases in licking behavior from the first to subsequent injection s of RTX, indicating the development of desensitization. Tetracaine-pr etreated rats showed equivalent or significantly greater decreases in licking behavior, suggesting that local anesthetic pretreatment either did not alter or enhanced development of desensitization to RTX. In a second experiment, tetracaine (0.25 or 0.5%) produced similar effects against a high dose of RTX (3.0 nmol), but did not consistently alter excitatory or desensitizing effects of a low dose of RTX (0.1 nmol). Similar results were obtained when rats were retested under the same c onditions 2 and 4 weeks later. This study demonstrates that pretreatme nt with a local anesthetic can attenuate the irritancy of initial trea tment with RTX without disrupting development of desensitization of se nsory afferents. Furthermore, the effects of both drugs are not dimini shed with repeated application.