Neurogenic dysfunction of external urethral sphincter (EUS) contraction and relaxation is a consequence of neurological pathology such as detrusor sphincter dyssynergia (increase of urethral resistance during voiding) after spinal cord injury (SCI) that disrupts central nervous system regulation of micturition reflexes. This results in dys-coordination between detrusor and EUS. A variety of neuromodulation approaches are developed to modulate the lower urinary tract (LUT) function by targeting the Onuf's nucleus located at lumbosacral levels. Here, we propose a novel method on stimulating spinal EUS relaxation controlling center by using epidural stimulation (EpS) to modulate EUS relaxation between storage and voiding phases. Spinal EUS relaxation controlling center will be identified by using EpS over several upper lumbar levels (L2-4) based on the previous publication (Chang et al., 2007) and preliminary results. Modulation of EUS relaxation controlling center by EpS possibly facilitates voiding by suppressing EUS tonic contraction, in other words, inhibits urethral resistance. After chronic SCI, a combination of EpS and serotonergic input promotes the suppression of EUS tonic contraction and further evokes the EUS relaxation during voiding. EpS of EUS relaxation controlling center provides the key for switching EUS activation between tonic contraction and relaxation. Functional assessment of LUT will be investigated to provide the information of voiding efficiency in the animals with neurogenic bladder dysfunction after chronic SCI. The proposed study focusing on EUS neuromodulation by using EpS (bioengineering aspect) and/or serotonergic modulation (pharmacological aspect) represents a cutting-edge research approach to improve LUT function with neurogenic bladder, and can be also used to reduce urethral resistance with impaired voiding contractions such as neurogenic bladder dysfunction of overactive and underactive bladders, peripheral nerve injuries, and aging.
The proposed project will examine the effect of epidural stimulation of external urethral sphincter (EUS) spinal relaxation controlling center located at L3 on modulating EUS contraction and relaxation in neurologically intact and spinal cord transected rats. An improved understanding of neuromodulation of spinal EUS relaxation controlling center combined with serotonergic modulation helps to understand the mechanisms of EUS activation during storage and voiding as well as to reduce urethral resistance with impaired detrusor contraction caused by neurological diseases/trauma, peripheral nerve injuries, and aging.
