Investigation and treatment of central nervous system dysfunction in chronic pelv

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DESCRIPTION (provided by applicant): The purpose of this protocol is to investigate the central nervous system dysfunction that is associated with chronic pelvic pain and also a possible novel treatment using a neuromodulatory tool - transcranial direct current stimulation (tDCS) - for this condition. This study is important as chronic pelvic pain can have a considerable impact in terms of interference with daily life activities and general well being which results in anxiety and depression. In addition, this condition has a relatively high prevalence - the prevalence rate of chronic pelvic pain in women in US is 3.7%, comparable with the numbers for other chronic conditions such as asthma (3.8%) and back pain (4.1%). Because chronic pelvic pain is often refractory to medical and surgical procedures and recent evidence suggests a central nervous system dysfunction - such as in the limbic areas (anterior cingulate cortex) - in chronic pelvic pain, we hypothesize that the pathophysiology of chronic pelvic pain is associated with abnormal activity in pain-related neural networks. This hypothesis is based on our pilot data showing that noninvasive brain stimulation (tDCS) induces a significant reduction in pain in these patients and also on our NIDDK-R03 funded study in which we showed that another technique of noninvasive brain stimulation reduces pain in chronic visceral pain due to pancreatitis and that changes in pain-related neural networks (as indexed by magnetic resonance spectroscopy) are found in these patients. Specifically, we will investigate the efficacy of tDCS in reducing pain in a cohort of chronic pelvic pain patients (with painful bladder syndrome or interstitial cystitis) via a phase-II, double-blinded, sham- controlled, parallel, randomized clinical trial and also assess the safety of this intervention via a battery of neurocognitive tests. Furthermore we will assess the impact of this treatment on the phenomenon of allodynia and hyperalgesia, which are known to be surrogates of central sensitization. Finally we will investigate the central neural dysfunction in these patients using the technique of magnetic resonance spectroscopy that can measure brain metabolites in a noninvasive and reliable manner. We hypothesize that our proposed intervention will reduce the pathological hyperactivity in the anterior cingulate gyrus in these patients. The results of this study may represent an important step for establishing a novel therapeutic approach for chronic pelvic pain and will also shed light on its pathophysiology. PUBLIC HEALTH RELEVANCE: Chronic pelvic pain results in a reduced quality of life, accounts for more than $2.8 billion dollars in direct annual healthcare expenses, and has indirect costs associated with absenteeism, reduced productivity, and hindered performance while at work. Patients who suffer from this painful, debilitating condition are often refractory to current pharmacological therapies. We therefore propose to investigate a novel therapeutic intervention using noninvasive brain stimulation and, in addition, investigate the neural basis of this disorder using magnetic resonance imaging - the results of this study will therefore provide insights into understanding the pathophysiology of chronic pelvic pain.