Abstract ID: A2
Abstract Title: TRPV1 Activation Contributes to Lipopolysaccharide-Induced Sensitization of Nociceptive Responses to Urinary Bladder Distension in Rats
Authors: Uzzell T1, Robbins M2, Ness T3
Univ of Alabama at Birmingham Birmingham AL
Poster Type: Poster
ABSTRACT BODY
Introduction: The vanilloid receptor 1 (TRPV1), a member of the transient receptor potential (TRP) superfamily, functions as a molecular integrator of nociceptive stimuli particularly in the presence of inflammation. It is highly expressed in afferent fibers that innervate the urinary bladder. We have previously demonstrated that visceromotor responses (VMRs) to urinary bladder distension (UBD) in TRPV1 null mice are unchanged following intravesical infusion of E. Coli-derived lipopolysaccharide (LPS), a treatment that mimicks a urinary tract infection. Taken together, these data suggest that activation of TRPV1 is involved in inflammatory pain of the bladder. Similar studies have not been performed in rats.
Materials and Methods: The present study examined the effect of capsazepine, a competitive TRPV1 receptor antagonist, on VMRs and cardiovascular responses to UBD in female Sprague-Dawley rats treated with intravesical LPS. Rats were briefly anesthetized with halothane, and a 22-gauge transurethral catheter was inserted. Saline or LPS (100 μg in 0.5 ml) was slowly infused into the bladder and left to dwell for 30 min. The next day, rats were reanesthetized with halothane, a tracheostomy performed and rats artificially ventilated. A transurethral catheter was again inserted and secured with ligatures around the urethra. Three electrodes were placed in the external oblique musculature and a carotic catheter placed. VMRs to UBD were measured as electromyographic recordings and cardiovascular responses were measured as changes in mean arterial pressure during UBD. Stable responses to UBD were established and responses to graded UBD (10-80 mm Hg, 20 s) were recorded. Capsazepine (50 μmole/kg) or vehicle solution were injected subcutaneously and subsequently responses to graded UBD were obtained.
Results: Both capsazepine and vehicle had effects on VMRs to UBD in saline and LPS-treated rats, but an inhibitory effect was profound and significantly greater in the LPS-treated rats. Effects of capsazepine on cardiovascular responses was limited.
Discussion: These findings further demonstrate the functional significance of TRPV1 activation to pain sensation in the bladder and suggest a role for TRPV1 antagonists in the treatment of visceral pain.
ATTACHED FILES
Reg Anesth Pain Med 2005; 30(3):A2