Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is a common and often debilitating condition. The underlying cause of CP/CPPS remains unknown. We recently published the first neuroimaging study comparing men with CP/CPPS to healthy men. We found that, most importantly, the functional connectivity between a brain motor region that activates pelvic floor muscles and a viscerosensory region in the right posterior insula was significantly reduced in men with CP/CPPS compared to healthy men. This prior work suggests that understanding this sensorimotor functional connection, which we term pelvic-motor/right- posterior-insula functional connectivity, may be critical to understanding the pathophysiology of CP/CPPS. However, we still do not fundamentally know how resting brain function influences active sensorimotor control. In the proposed work, we aim to fill this knowledge gap by relating pelvic-motor/right-posterior-insula functional connectivity to automatic pelvic floor muscle activation during voluntary activation of non-pelvic floor muscles in men with and without CP/CPPS. We will recruit 52 men with CP/CPPS and 52 healthy men. In each participant, we will use resting-state functional Magnetic Resonance Imaging (rs-fMRI) to quantify pelvic-motor/right- posterior-insula functional connectivity, surface EMG to quantify automatic pelvic floor muscle activation during voluntary gluteal muscle activation, and questionnaires to quantify CP/CPPS pain intensity. rs-fMRI, EMG, and pain measures will be analyzed with the following Aims.
In Aim 1, we will study inter-individual differences in men and determine if reduced pelvic-motor/right-posterior-insula functional connectivity correlates with increases in the magnitude of automatic pelvic floor muscle activation during voluntary activation of non-pelvic floor muscles.
In Aim 2, we will compare healthy men and men with CP/CPPS, whom we have shown to have a reduced value of resting state pelvic-motor/right-posterior-insula functional connectivity compared to healthy male controls. We will determine if men with CP/CPPS show corresponding increases in the magnitude of automatic pelvic floor muscle activation during voluntary activation of the gluteus maximus muscle, and if the magnitude of automatic pelvic floor muscle activation is correlated with the intensity of CP/CPPS pain. This work, to our knowledge, represents the first study relating resting brain function to the magnitude of automatic muscle activation during movement. This work is also the first study proposing to test a specific mechanism of altered pelvic floor muscle control in men with CP/CPPS. Our prior work defined a brain connection of interest in men with CP/CPPS. Our proposed work will determine if this brain connection is related to altered movement control. Our future work will be able to then examine modifying movement control as an approach to restoring normal brain function in men with CP/CPPS.

Public Health Relevance

Our pelvic floor muscles provide the support and control that is necessary for voluntary and involuntary movement. Millions of men suffer from chronic uncontrollable pain in the region of the pelvic muscles - impacting everything from bowel/bladder function to sexual function to physical activity - causing a greatly reduced quality of life. In this project, we will test the hypothesis that men with chronic pelvic pain have changes in resting brain function associated with changes in muscle control underlying the dysfunction in this disorder, laying the groundwork for future treatment studies.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
5R01DK110669-04
Application #
9896815
Study Section
Motor Function, Speech and Rehabilitation Study Section (MFSR)
Program Officer
Mullins, Christopher V
Project Start
2017-02-01
Project End
2021-01-31
Budget Start
2020-02-01
Budget End
2021-01-31
Support Year
4
Fiscal Year
2020
Total Cost
Indirect Cost
Name
University of Southern California
Department
Dentistry
Type
Schools of Dentistry/Oral Hygn
DUNS #
072933393
City
Los Angeles
State
CA
Country
United States
Zip Code
90089
Yani, Moheb S; Wondolowski, Joyce H; Eckel, Sandrah P et al. (2018) Distributed representation of pelvic floor muscles in human motor cortex. Sci Rep 8:7213