Use of Optical Mapping to Evaluate Mechanisms and New Therapies for Bladder Dysfunction Due to Spinal Cord Injury
Abstract
Treatments for lower urinary tract dysfunctions, due to spinal cord injury (SCI), are typically ineffective or have unacceptable side effects. Our project focused on identifying new therapeutic options to treat SCI-induced afferent sensitization and bladder overactivity using a T8-T9 spinal cord transected mouse model. These included phosphodiesterase type-5 (PDE5) inhibitors, 3-adrenoceptor agonists, botulinum neurotoxin type-A (BTX-A), tibialnerve stimulation (TNS) neuromodulation and a p75 neurotrophin receptor antagonist. Our studies suggest that PDE5 inhibition is beneficial by increasing nitric oxide levels that uncouple interstitial cells driving bladder overactivity. They also decrease afferent nerve firing and thus help alleviate the sensory component in SCI induced detrusor overactivity. 3-adrenoceptor agonists were effective in treating neurogenic and myogenic bladder overactivity by suppressing nociceptive c-fibers, but not stretch-sensitive A-fibers. BTX-A was effective insuppressing only neurogenic bladder overactivity. TNS neuromodulation was ineffective in treating animals without an intact spinal cord (i.e., transected). The p75 receptor antagonist, LM11A-31, had the most therapeutic benefits and was effective in preventing/treating bladder overactivity, loss the urothelial barrier, detrusor hypertrophy, and development of detrusor sphincter dyssynergia (DSD).
Document Details
- Document Type
- Technical Report
- Publication Date
- Dec 01, 2014
- Accession Number
- AD1007699
Entities
People
- Anthony J Kanai
Organizations
- University of Pittsburgh