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（由申请人提供）：慢性疼痛仍然是影响超过 1 亿美国人的一个重要问题。了解慢性疼痛的一个关键特征是其演变和退化的性质（即，最常涉及的疾病或治疗恢复力）。周围神经建立级联，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合并症出现的基础。我们将在一项纵向研究中评估踝关节损伤后神经性疼痛模型中的（1）反应者和无反应者中的这些措施。超过 12 个月或 (2) 疼痛持续超过 12 个月的治疗抵抗受试者在此过程中，我们将定义那些仍难以恢复的大脑变化以及那些与恢复有关的变化，并将神经改变与大脑联系起来。变化。为了开展该项目，我们提出以下具体目标： 目标 1：神经性疼痛的演变和转移的神经和大脑测量 目标 2：疼痛相关脆弱性（恐惧）和复原力（自我效能）的心理过程。预测神经性疼痛的恢复目标 3：治疗抵抗患者的塑性​​与非塑性变化我们发现神经性疼痛的恢复与外周疼痛的缓解相关。神经损伤以及特定大脑网络的正常化，并且慢性化与适应不良的大脑网络的持续存在有关，这导致情绪回路的持续招募和治疗抵抗。出于多种原因，我们将在青少年受试者中进行这项研究。包括：(a) 踝关节扭伤的发病高峰发生在 15 岁至 19 岁之间，男性和女性的发病率相同；(b) 恢复速度通常很快，即使处于慢性状态，儿童对治疗的抵抗力也较低；作为成年人，从而允许数据我们有能力在更短的时间内收集数据，因为：（1）我们评估慢性疼痛儿科患者大脑变化的能力；（2）技术精湛且经验丰富的多学科研究团队； (3) 我们小组获得的初步结果表明我们有能力进行所提出的实验，这项研究计划的成功结果将为了解疼痛缓解和疼痛慢性化的大脑机制以及评估神经损伤的新型快速非侵入性过程提供见解。这些方法可以在儿童和持续疼痛的预测因素中发挥作用。快速、轻松地融入临床或临床试验。