W. Stuart Reynolds ¹, Alvaro Lucioni ¹, David E. Rapp ¹, Gregory T. Bales ¹, Daniel S. McGehee ²

¹Department of Urology, ²Department of Anesthesia & Critical Care, University of Chicago, Chicago, IL

Introduction: Clinical and scientific data suggest that anti-muscarinic anticholinergic medications most commonly used to treat overactive bladder symptoms have effects on sensory nerves in addition to their familiar motor neuron activity. Calcitonin Gene-Related Peptide (CGRP) is a sensory neuropeptide commonly used as a marker of afferent nerve activity. We sought to evaluate the hypothesis that anticholinergic medications exert an inhibitory effect on sensory actions of the bladder in conditions of inflammation. Accordingly, the effects of tolterodine and solifenacin on the release of CGRP in an acute injury rat bladder model were studied.

Methods: Whole rat bladders were incubated in a series of tissue baths containing physiological salt solution (PSS). To induce bladder injury and evoke CGRP release, bladders were incubated in PSS containing HCl (0.04M). To measure the effect of anticholinergics on bladder injury, the tissue was incubated in an organ bath containing tolterodine, solifenacin or vehicle either before (pre-incubation group) or following (post-incubation group) HCl exposure. A dose of (100µM) was used for solifenacin studies. Doses ranging from 1µM to 500µM were used for tolterodine study to assess the effect of dose on drug action. CGRP release was determined by radioimmunassy.

Results: Mean baseline release of CGRP ± SEM was 9.5 ± 0.65 pg/gm for the pre-incubation group and 38 ± 8 pg/gm for the post-HCl incubation group. Exposure to HCl increased CGRP release by 90% over baseline for both arms (545 ± 101 pg/gm, p < 0.038 for pre-incubation and149 ± 28 pg/gm, p < 0.003 for post-HCl incubation). Application of either tolterodine or solifenacin did not affect the release of CGRP in either the pre- or post-incubation groups when compared with controls.

Conclusions: Neither tolterodine nor solifenacin inhibited the release of CGRP from afferent nerve terminals in an acute injury rat bladder model. Accordingly, the actions of anticholinergic medications on sensory neurons described by other authors may not occur through transient receptor potential (TRP)-mediated pathways. Further investigation of anticholinergic actions on purinergic- and neurokinin- mediated pathways is needed.

UroToday.com Coverage of SUFU 2007

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