Brain imaging based strategies for treating UCPPS pain

描述(申请人提供)：这是一份为期一年的R01申请，是对RFA-DK-12-025《泌尿系统慢性盆腔疼痛综合征(UCPPS)研究》(R01)的回应。目前还没有有效的治疗UCPPS的方法。来自慢性盆腔疼痛多学科研究(MAPP)研究网络的最新初步结果表明，UCPPS男性患者存在整体和局部大脑解剖和功能异常。因此，重整化的泌尿系疼痛相关脑重组是治疗UCPPS的一个可行和客观的靶点。我们最近在其他慢性疼痛条件下进行的人体研究表明，在某些患者中，单独使用安慰剂可能是一种有效的治疗方法。此外，我们的动物研究表明，D-环丝氨酸(DC，针对额叶皮质)可以逆转啮齿类动物神经病理性疼痛的许多迹象。这些结果表明，通过安慰剂和通过DC来缓解泌尿系统疼痛是UCPPS的潜在治疗选择，每一种都可能通过不同的大脑回路来调节。在这里，我们在一项双盲、三臂、基于脑成像的随机临床试验中，对患有UCPPS的男性患者进行了双盲、三臂、基于脑成像的随机临床试验，以相互比较和不治疗为对照，测试了DCS和安慰剂的疗效。重复监测大脑解剖和功能，通过问卷调查和使用智能手机App(在日常生活的自然环境中收集疼痛评级，每天3次)测量泌尿系疼痛。参与者经历了两周的观察期，三个月的治疗期，两周的洗涤期，以及最后一段时间，参与者选择继续接受两种治疗中的一种，再持续一个月。这项试验将使我们能够解决三个具体目标：目标1：评估安慰剂和DC之间对UCPPS泌尿系统疼痛缓解的不同疗效。目的2：评价不同的脑功能生物标记物对治疗反应和治疗倾向的影响，包括安慰剂和弥漫性脑脊髓炎。目的3：证明治疗应答者的脑形态重整化。鉴于RFA的资金和时间限制，这项研究的目的是验证概念，并证明在评估UCPPS中的新疗法时，该方法在为个体化治疗选择提供客观证据方面的力量。

DESCRIPTION (provided by applicant): This is a one-year R01 application in response to RFA-DK-12-025 entitled Urologic Chronic Pelvic Pain Syndrome (UCPPS) Research (R01). There are no effective treatments for UCPPS. Recent preliminary results from the Multi-Disciplinary Approach to the Study of Chronic Pelvic Pain (MAPP) Research Network indicate global and local brain anatomical and functional abnormalities in men with UCPPS. Thus, renormalization of the urological pain-related brain reorganization is a viable and objective target for treating UCPPS. Our recent human studies in other chronic pain conditions indicate that placebo alone may be an efficient treatment in some patients. Also, our animal studies show that D-cycloserine (DCS, targeting the frontal cortex) can reverse many of the signs of neuropathic pain in rodents. These results indicate that urological pain relief by placebo and by DCS are potential therapy options for UCPPS, each of which may be mediated through distinct brain circuitry. Here we test the efficacy of DCS and placebo, in comparison to each other and to no-treatment, in a double blind, three-armed, brain imaging-based randomized clinical trial in men with UCPPS. Brain anatomy and function are monitored repeatedly, and urological pain is measured with questionnaires and using a smart phone App (to collect pain ratings in the natural setting of everyday life, 3 times a day). Participants undergo a 2-week observation period, a 3-month treatment period, a 2-week washout period, and a final period wherein participants choose to continue on one of the two treatments for another month. The trial will permit us to address three specific aims: Aim 1: Evaluate differential efficacy for UCPPS urological pain relief between placebo and DCS. Aim 2: Evaluate differential brain functional biomarkers for treatment response and treatment propensity, for placebo and for DCS. Aim 3: Demonstrate that brain morphology renormalizes in treatment responders. Given the financial and time constraints of this RFA, the study is powered to be a proof of concept and to demonstrate the strength of the methodology in providing objective evidence for individualized treatment choices when evaluating novel therapies in UCPPS.