Motor cortical neuromodulation in women with Interstitial Cystitis/Bladder Pain Syndrome: reducing pain by improving brain and muscle activity

患有间质性膀胱炎/膀胱疼痛综合征的女性的运动皮质神经调节：通过改善大脑和肌肉活动来减轻疼痛

• 批准号: 10655675
• 负责人: Jason J. Kutch
• 金额: $ 62.26万
• 依托单位: UNIVERSITY OF SOUTHERN CALIFORNIA
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-08-15 至 2025-04-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10655675
• 关键词: Area; Bladder; Brain; Brain region; Chronic; Clinical Trials; Data; Disease remission; Enrollment; Esthesia; Frequencies; Functional Magnetic Resonance Imaging; Functional disorder; Future; Goals; Individual; Interstitial Cystitis; Laboratories; Link; Literature; Measures; Mediating; Mediation; Modeling; Motor; Motor Cortex; Muscle; Outcome Measure; Pain; Participant; Patients; Pelvic Floor Muscle; Pelvic floor structure; Pelvis; Physical therapy; Play; Protocols documentation; Publishing; Randomized; Reporting; Rest; Role; Symptoms; Testing; United States; Woman; Work; activity marker; chronic pain; comparison group; effective therapy; imaging study; improved; improved functioning; innovation; interest; neuromechanism; neuromuscular; neuroregulation; noninvasive brain stimulation; pain reduction; recruit; repetitive transcranial magnetic stimulation; theories

PROJECT SUMMARY Interstitial Cystitis/Bladder Pain Syndrome (IC/BPS) is a common, chronic, and debilitating condition in women. The underlying cause of IC/BPS remains unknown. We recently published the first functional magnetic resonance imaging (fMRI) study comparing brain function in women with IC/BPS to healthy women. We found that women with IC/BPS have altered resting activity in supplementary motor area (SMA). Specifically, these changes appear in a part of SMA that we have shown to control pelvic floor muscle activity (“pelvic-SMA”). Our results provide the first explanation for extensive published reports of increased pelvic floor muscle activity in women with IC/BPS. We hypothesize that we are observing evidence of an important theory of chronic pain: motor cortical changes occur that are initially beneficial to increase protective muscle activity but are ultimately maladaptive and perpetuate pain. Our goal is to reduce pain by improving brain activity and pelvic muscle activity (making them more similar to healthy individuals). Using non-invasive repetitive transcranial magnetic stimulation (rTMS) directed at pelvic-SMA, we aim to determine if we can reduce pain (Aim 1), improve resting brain activity (fMRI) and resting pelvic floor muscle electromyographic (EMG) activity in IC/BPS (Aim 2), and to link the pain reductions to fMRI/EMG improvements to develop a causal mediation model of IC/BPS symptoms (Aim 3). We will recruit 75 women with IC/BPS to participate in the study, and participants will be randomized to 3 groups of 25 to test different rTMS paradigms: high-frequency (to increase excitability), low-frequency (to decrease excitability), and sham (as a control). Our preliminary data suggest that high-frequency stimulation is the best protocol since it improves resting pelvic-SMA activity while reducing pain and pelvic muscle activity. These results are convergent with an independently-published preliminary study that suggests that 5 consecutive days of high-frequency stimulation can reduce IC/BPS pain relative to sham, even measured 3 weeks after the cessation of stimulation. We will extend these preliminary findings in the proposed work: in the high-frequency and sham rTMS groups, we will study 5 consecutive days of stimulation with both shorter-term outcome measures (associated with the first day of stimulation) and longer-term outcome measures (3 weeks after the cessation of stimulation). In the low-frequency rTMS group, we will only examine shorter-term outcome measures associated with a single session, since our preliminary data suggest that low-frequency stimulation is active but perturbs pelvic-SMA and resting pelvic floor muscle activity away from values associated with healthy controls and does not reduce pain. Our preliminary results agree with a large body of literature suggesting that high-frequency rTMS applied to motor cortex is the best rTMS paradigm to reduce pain. However, our proposed work has the potential to greatly innovate the field of brain stimulation for pain by using sham and active comparison groups, as well as objective fMRI/EMG outcome measures, to define the mechanism by which high-frequency stimulation can improve deficiencies in motor function in chronic pain.

项目总结