Central and Peripheral Measures of Pain: Recovery and Resistance

中枢和外周疼痛测量：恢复和抵抗

• 批准号: 8986369
• 负责人: DAVID BORSOOK
• 金额: $ 69.44万
• 依托单位: BOSTON CHILDREN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-07-01 至 2020-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8986369
• 关键词: Adolescence; Adolescent; Adult; Affect; Age-Years; American; Amygdaloid structure; Ankle; Ankle Injuries; Anterior; Athletic Injuries; Behavioral; Brain; Caring; Chemicals; Chemistry; Child; Chronic; Clinic; Clinical; Clinical Trials; Cognitive; Comorbidity; Data; Disease; Emotional; Emotions; Evolution; Female; Fright; Future; Grant; Hippocampus (Brain); Human Resources; Image; Incidence; Injury; Interdisciplinary Study; Longitudinal Studies; Measures; Medical; Mental Depression; Modeling; Nature; Nerve; Neurobiology; Nucleus Accumbens; Outcome; Outcomes Research; Pain; Patients; Peripheral; Peripheral Nerves; Peripheral nerve injury; Persistent pain; Phenotype; Plastics; Positioning Attribute; Prefrontal Cortex; Process; Psychological desensitization therapy; Recovery; Rehabilitation therapy; Research; Research Proposals; Resistance; Resolution; Rewards; Self Efficacy; Sensory; Source; Sprain; Structure; Teenagers; Testing; Time; Visit; base; chronic pain; cingulate cortex; cohort; experience; gray matter; illness length; injured; insight; male; midbrain central gray substance; nerve injury; novel; painful neuropathy; pediatric patients; psychologic; public health relevance; research study; resilience; reward circuitry; sciatic nerve; standard care; time interval

 DESCRIPTION (provided by applicant): Chronic pain continues to be a significant problem affecting over 100 million Americans. One key feature to understanding chronic pain is the nature of its evolution and devolution (i.e., disease or treatment resilience). Neuropathic pain most frequently involves the peripheral nervous that sets up a cascade that produces functional, morphological and chemical changes in the brain. These changes may underlie chronification and the emergence of comorbidity such as depression. Here we propose to measure alterations in peripheral nerve and brain and correlate these with psychological measures for fear and self-efficacy that may predict outcome. We will evaluate these measures in (1) responders and non-responders in a model of neuropathic pain following ankle injury in a longitudinal study over 12 months or (2) treatment resistant subjects who have had their pain for greater than 12 months. In doing so we will define those brain changes that remain resistant to recovery and those that are implicated in recovery and we will correlate nerve alterations with brain changes. In order to carry out the project we propose the following specific aims: Aim 1: Nerve and Brain Measures of the Evolution and Devolution of Neuropathic Pain. Aim 2: Psychological Processes of Pain- Related Vulnerability (Fear) and Resilience (Self-Efficacy) Predict Recovery from Neuropathic Pain. Aim 3: Plastic vs. Non-Plastic Changes in Treatment Resistant Patients. We hypothesize that recovery from neuropathic pain is associated with resolution of peripheral nerve damage as well as normalization of specific brain networks and that chronification is related to the ongoing presence of maladaptive brain networks that contribute to the ongoing recruitment of emotional circuitry and treatment resistance. We will carry out the study in teenage subjects for a number of reasons including: (a) the peak incidence of ankle sprain occurs between fifteen and nineteen years of age and equal incidence occurs in males and females; (b) the recovery profile is usually rapid and even in the chronic state children are not as resistant to treatment as adults, thus allowing for data to be collected over a shorter time. We are well positioned to execute the Aims of the study based on: (1) our ability to evaluate brain changes in pediatric patients with chronic pain; (2) a highly skilled and experienced multidisciplinary research team; and (3) preliminary results obtained from our group that demonstrate our ability to carry out the proposed experiments. The successful outcome of this research proposal will provide insights into brain mechanisms of pain relief and pain chronification, novel rapid non- invasive processes for evaluating nerve damage in children and predictors of ongoing pain. These approaches could be rapidly and easily integrated into the clinic or clinical trials.

 描述（由应用程序提供）：慢性疼痛仍然是影响超过1亿美国人的重大问题。了解慢性疼痛的一个关键特征是其进化和下放的性质（即疾病或治疗弹性）。神经性疼痛最常涉及周围神经，该神经神经是在大脑中产生功能，形态和化学变化的级联反应。这些变化可能是回归和合并症（例如抑郁症）的出现的基础。在这里，我们建议衡量周围神经和大脑的改变，并将其与心理措施相关联，以预测可能预测结果的恐惧和自我效能感。我们将在12个月内的纵向研究中，在踝关节损伤后的神经性疼痛模型中评估（1）反应者和非反应者中的这些措施，或者（2）耐药的受试者疼痛超过12个月。通过这样做，我们将定义那些对恢复抗恢复能力的大脑变化以及在恢复中实施的大脑变化，我们将与大脑变化相关联。为了执行该项目，我们提出了以下特定目的：目标1：神经性疼痛进化和下放的神经和脑测量。目标2：与疼痛相关的脆弱性（恐惧）和韧性（自我效能感）的心理过程预测神经性疼痛的恢复。 AIM 3：塑性与非塑性变化的抗治疗患者。我们假设从神经性疼痛中恢复与解决周围神经损害以及特定脑网络的归一化有关，并且编年期与不断恶化的脑网络的存在有关，这有助于持续募集情绪电路和耐药性。由于多种原因，我们将在青少年受试者中进行研究，包括：（a）踝关节喷雾的峰值发生在15至19岁之间，男性和女性发生； （b）恢复曲线通常很快，即使在慢性状态儿童中也不像成年人那样抵抗治疗，因此可以在较短的时间内收集数据。基于：（1）我们评估慢性疼痛儿科患者大脑变化的能力； （2）一个高技能和经验丰富的多学科研究团队； （3）从我们的小组中获得的初步结果，证明了我们进行提出的实验的能力。这项研究建议的成功结果将为您提供有关缓解疼痛和疼痛的大脑机制的见解，新型的快速非侵入性过程，用于评估儿童的神经损害以及持续疼痛的预测指标。这些方法可以迅速易于整合到临床或临床试验中。