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Use of Optical Mapping to Evaluate Mechanisms and New Therapies for Bladder Dysfunction Due to Spinal Cord Injury

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Annual rept. 30 Sep 2012-29 Sep 2013

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There are 300,000 individuals in the United States with spinal cord injury SCI, where 22 are veterans 1,2. While their quality of life is significantly affected by lower urinary tract symptoms LUTS, most treatments are palliative or ineffective. We focused on the therapeutic benefits of 3 adrenoceptor agonists, botulinum neurotoxin type A BTX-A intradetrusor injections and their combination. BTX-A inhibits neurotransmitter release from nerve terminals. This has therapeutic effects on bladder dysfunction by inhibiting parasympathetic nerves to decrease reflex contractions, and afferent nerves, to reduce sensory symptoms. However, by also inhibiting sympathetic nerves, BTX-A decreases norepinephrine release and stimulation of detrusor 3 adrenoceptors thereby decreasing relaxation and bladder compliance. Accordingly, we assessed the effects of BTX-A and 3 adrenoceptor agonists in combination. In control mice, 3 agonists had little effect as 3 adrenoceptors are not normally expressed in mice. In SCI mice, 3 agonists were beneficial by abolishing intrinsic bladder contractions and enhancing bladder compliance suggesting that 3 adrenoceptors are upregulated in pathology. In BTX-A treated SCI mice, 3 agonists significantly improved bladder compliance compromised by the toxin. Thus, 3 adrenoceptor agonists in combination with BTX-A are beneficial in improving bladder function in SCI patients.

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  • Medicine and Medical Research

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