Use of Optical Mapping to Evaluate Mechanisms and New Therapies for Bladder Dysfunction Due to Spinal Cord Injury
Abstract
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.
Document Details
- Document Type
- Technical Report
- Publication Date
- Oct 01, 2013
- Accession Number
- ADA592896
Entities
People
- Anthony J Kanai
Organizations
- University of Pittsburgh