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(申请人提供)：慢性疼痛仍然是一个严重的问题，影响着超过1亿的美国人。了解慢性疼痛的一个关键特征是其演变和转移的性质(即疾病或治疗弹性)。神经病理性疼痛最常见的是周围神经，它建立了一个级联反应，在大脑中产生功能、形态和化学变化。这些变化可能是慢性化和抑郁症等共病出现的基础。在这里，我们建议测量周围神经和大脑的变化，并将这些变化与可能预测结果的恐惧和自我效能的心理测量相关联。我们将在(1)在一项超过12个月的纵向研究中评估(1)踝关节损伤后神经病理性疼痛模型中的应答者和无应答者，或(2)疼痛超过12个月的治疗抵抗受试者。在这样做的过程中，我们将定义那些仍然无法恢复的大脑变化和那些与恢复有关的变化，我们将把神经变化与大脑变化联系起来。为了开展该项目，我们提出了以下具体目标：目标1：神经病理性疼痛演变和消退的神经和大脑测量。目的2：疼痛相关易损性(恐惧)和韧性(自我效能)的心理过程预测神经病理性疼痛的康复。目的3：治疗耐药患者中塑料与非塑料的变化。我们假设神经病理性疼痛的恢复与周围神经损伤的解决以及特定脑网络的正常化有关，而时序化与持续存在的适应不良脑网络有关，后者有助于持续招募情绪回路和治疗阻力。我们将在青少年受试者中进行这项研究，原因包括：(A)脚踝扭伤的高峰发生在15至19岁之间，男性和女性的发病率相等；(B)恢复情况通常很快，即使在慢性疾病状态下，儿童也不像成年人那样对治疗具有抵抗力，因此可以在较短的时间内收集数据。我们处于有利地位，能够执行研究的目标，其依据是：(1)我们评估患有慢性疼痛的儿科患者的大脑变化的能力；(2)高技能和经验丰富的多学科研究团队；以及(3)从我们团队获得的初步结果，证明我们有能力进行拟议的实验。这项研究提案的成功结果将为深入了解疼痛缓解和疼痛时代化的大脑机制、评估儿童神经损伤的新的快速非侵入性过程以及持续疼痛的预测因素提供见解。这些方法可以快速、轻松地整合到临床或临床试验中。