Behavioral and Neural Phenotypes of Primary Dysmenorrhea in Adolescents

项目摘要/摘要 慢性疼痛是一个重大且代价高昂的公共卫生问题，导致国家经济负担 每年3000亿美元。识别那些有慢性疼痛风险的人的生物标志物在很大程度上是未知的。 原发性痛经(PD)，定义为月经疼痛，没有确定的器质性原因，是一种独特的 研究疼痛过程的人群，因为患有帕金森病的女性反复出现明确的疼痛发作，并 否则就没有痛苦了。数据显示，患有帕金森病的女性与患有帕金森氏症的患者具有相似的疼痛生物标志物 慢性疼痛，包括增强的疼痛敏感性。因为帕金森氏症在青春期就开始了--一个关键的 与建立神经通路和完善大脑网络连接相关的发育阶段- 前瞻性地确定内源性疼痛处理以及脑结构和连接性的变化 人口可以提供有关疼痛慢化机制的关键信息。这是 关键的下一步是设计有针对性的个性化治疗，以防止有风险的人 持续的疼痛和残疾。 这项拟议的研究将使用PD作为模型来检查与月经和非月经相关的生物标志物 14-18岁青春期女孩的月经-身体疼痛，她们将接受包括疼痛在内的广泛表型 抑制试验和多模式神经成像以获得灰质形态计量学指标，微结构 脑白质的完整性，解剖(扩散张量成像)和功能(静息状态的磁性 磁共振成像)在基线和12个月后的连接性。月经疼痛严重程度和非经期 身体疼痛将在24个月内每月评估一次。我们的目标是：1)确定帕金森病的中枢机制 疼痛抑制和大脑结构以及感觉运动的连通性、默认、情绪唤醒、 和显著网络，2)确定疼痛抑制的缺陷和大脑结构和网络的改变 预测月经疼痛和非月经体痛一年发展轨迹的连通性 疼痛，以及3)确定疼痛抑制和脑结构变化之间的动态关系 月经性疼痛和非经期躯体疼痛与症状变化的相关性。我们假设 内源性疼痛抑制缺陷和脑结构、连通性和大脑区域功能的改变 网络将与基线的月经疼痛严重程度评级呈正相关，并预测轨迹 超过2年的经期和非经期身体疼痛。成像数据将使用图论进行分析 方法，并综合数据分析一般线性和一般线性混合模型。结果是 预计将确定预测从急性/周期性过渡的具体机制和特征 从疼痛到持续性或慢性疼痛，这将支持认知行为等治疗方法的发展 治疗或经颅直流电刺激，以防止从复发到慢性疼痛的过渡 成人期。

Project Summary/Abstract Chronic pain is a significant and costly public health concern, resulting in a national economic burden of $300 billion annually. Biomarkers identifying those at risk for developing chronic pain are largely unknown. Primary dysmenorrhea (PD), defined as menstrual pain without an identified organic cause, is a unique population for studying pain processes, as women with PD have repeated, defined episodes of pain and are otherwise pain-free. Data suggest that women with PD share similar pain biomarkers with individuals with chronic pain, including enhanced pain sensitivity. Because PD begins in adolescence – a critical developmental phase associated with establishing neural pathways and refining brain network connectivity – prospectively identifying alterations in endogenous pain processing and brain structure and connectivity in this population can provide critical information about mechanisms involved in the chronification of pain. This is the crucial next step to designing targeted, individualized treatments to prevent those at risk from developing ongoing pain and disability. The proposed study will use PD as a model to examine biomarkers associated with menstrual and non- menstrual bodily pain in adolescent girls, ages 14-18, who will undergo extensive phenotyping including pain inhibition testing and multimodal neuroimaging to obtain indices of gray matter morphometry, microstructural integrity of white matter, and anatomical (diffusion tensor imaging) and functional (resting state magnetic resonance imaging) connectivity at baseline and 12 months later. Menstrual pain severity and non-menstrual bodily pain will be assessed monthly for 24 months. We aim to 1) identify the central mechanisms of PD using measures of pain inhibition and brain structure and connectivity of sensorimotor, default, emotional arousal, and salience networks, 2) determine deficits in pain inhibition and alterations in brain structure and network connectivity that predict the one-year developmental trajectories of menstrual pain and non-menstrual bodily pain, and 3) identify the dynamic relationship between alterations in pain inhibition and brain structure and connectivity with symptom change in menstrual pain and non-menstrual bodily pain. We hypothesize that deficits in endogenous pain inhibition and alterations in brain structure, connectivity, and function of regional networks will be positively associated with menstrual pain severity ratings at baseline and predict the trajectory of menstrual and non-menstrual bodily pain over 2 years. Imaging data will be analyzed using graph theoretical approaches, and comprehensive data analyses general linear and general linear mixed models. The results are expected to identify specific mechanisms and characteristics that predict the transition from acute/cyclical pain to persistent or chronic pain, which will support the development of therapies, such as cognitive-behavior therapy or transcranial direct current stimulation, to prevent the transition from recurrent to chronic pain in adulthood.