Pelvic floor muscles (PFM) form a dome-shaped muscle complex are critical in urinary continence, defecation and sexual functions, and weakening pelvic floor muscles can cause uncontrolled detrusor activity, urgency, and urinary incontinence (UI), a condition that affects 30-60% of women in the US. Recently, there is an increasing appreciation for the importance of the specific pattern of activity of antagonistic muscles in the pelvic floor, and a realization that dysfunctional timing, reduced amplitude or disorganized pattern of activity in individual muscles, critically impact their ability to maintain the urethra closed, resulting in urine leakage. Here, we hypothesize that selective and coordinated stimulation of individual PFM nerves will re-establish their normal strength and activity patterns, effectively reversing the symptoms of UI. To that end, we have established a rabbit model of UI that replicates several aspects of the human condition, including the specific pattern of activation of individual levator ani and perineal muscles during the storage and voiding phases. This proposal is innovative in that it uses a state-of-the-art miniaturized wireless electrodes to enable the interfacing of small PFM efferent nerves and directly modulate their individual activity. Our preliminary studies show that compromised micturition resulting from altered PFMs activity caused by multi-parity or aging in rabbits, can be reversed using selective PFM neuromodulation (SPNM). We specifically seek to: 1) define the activation parameters for maximal muscle force and limited fatigue for individual PFM, 2) evaluate the efficacy of patterned PFM activity by SPNM in young multiparous and aging multiparous animals, and 3) demonstrate that chronic electrical stimulation of PFM nerves can improved UI symptoms long-term, and test if that SPNM benefit persists after discontinuing the neuromodulation treatment. This proposal will provide new information on the physiological role of the PFM in urinary function, and will evaluate the selective neuromodulation of these muscles as a potential therapy for drug resistant UI.

Public Health Relevance

Damage to pelvic floor muscles (PFM) often leads to alterations in their individual activity pattern, which is believed to contribute to some forms of urinary incontinence. This study aims to define the electrical stimulation pattern for individual PFM in micturition. It also proposes the use of miniature wireless neurotechnology for selective neuromodulation of the individual PFM as a strategy to re- establish their normal strength and activity patterns in multiparous and aging animals with urinary incontinence. This study will contribute to our understanding of the individual PFM in pelvic floor pathology, and evaluates the use of selective pelvic floor neuromodulation as a potential therapy for urinary incontinence. + + 1+

National Institute of Health (NIH)
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Research Project (R01)
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Special Emphasis Panel (ZRG1)
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Mullins, Christopher V
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University of Texas-Dallas
Biomedical Engineering
Biomed Engr/Col Engr/Engr Sta
United States
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