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: 10011870
• 负责人: Daniel S Kohane
• 金额: $ 67.66万
• 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 2022-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10011870
• 关键词: Adolescent; Adult; Affect; Age-Years; American; Amygdaloid structure; Ankle; Ankle Injuries; Anterior; Athletic Injuries; Behavioral; Brain; Caring; Chemicals; Child; Chronic; Clinic; Clinical; Clinical Trials; Cognitive; Data; Disease; Emotional; Emotions; Evolution; Female; Fright; Future; Grant; Hippocampus (Brain); Human Resources; Incidence; Injury; Interdisciplinary Study; Longitudinal Studies; Measures; Medical; Mental Depression; Modeling; Morphology; Nature; Nerve; Neurobiology; Nucleus Accumbens; Outcomes Research; Pain; Patients; Peripheral; Peripheral Nerves; Peripheral nerve injury; Persistent pain; Phenotype; Positioning Attribute; Prefrontal Cortex; Process; Psychological desensitization therapy; Recovery; Research; Research Proposals; Resistance; Resolution; Rewards; Self Efficacy; Sensory; Source; Sprain; Structural Chemistry; Teenagers; Testing; Time; Visit; base; brain abnormalities; chronic pain; chronic pain patient; cingulate cortex; cohort; comorbidity; experience; experimental study; gray matter; illness length; imaging biomarker; insight; male; midbrain central gray substance; nerve damage; nerve injury; novel; outcome prediction; pain chronification; pain rehabilitation; pain relief; painful neuropathy; pediatric patients; peripheral nerve damage; prospective; psychologic; public health relevance; recruit; resilience; responders and non-responders; reward circuitry; sciatic nerve; standard care; therapy resistant; 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1亿美国人的重要问题。理解慢性疼痛的一个关键特征是其演变和退化的性质（即，疾病或治疗弹性）。神经性疼痛最常涉及外周神经，其建立级联反应，在脑中产生功能、形态和化学变化。这些变化可能是慢性化和抑郁症等并发症出现的基础。在这里，我们建议测量周围神经和大脑的变化，并将这些与恐惧和自我效能的心理测量相关联，这些测量可以预测结果。我们将在（1）12个月的纵向研究中踝关节损伤后神经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中评价这些指标。在这样做的过程中，我们将定义那些仍然抵抗恢复的大脑变化，以及那些与恢复有关的大脑变化，我们将把神经变化与大脑变化联系起来。为了实施该项目，我们提出了以下具体目标：目标1：神经和大脑的神经病理性疼痛的演变和发展的措施。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。目的3：难治性患者的塑料与非塑料变化。我们假设，神经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，慢性化与持续存在的适应不良的脑网络有关，这些网络有助于持续招募情绪回路和治疗抵抗。我们将在青少年受试者中进行研究，原因包括：（a）踝关节扭伤的高峰发生在15 - 19岁之间，男性和女性的发病率相同;（B）恢复通常很快，即使在慢性状态下，儿童也不像成人那样对治疗有抵抗力，因此可以在较短的时间内收集数据。我们有能力执行这项研究的目的，基于：（1）我们评估慢性疼痛儿科患者大脑变化的能力;（2）一个高度熟练和经验丰富的多学科研究团队;（3）从我们小组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提供对疼痛缓解和疼痛慢性化的大脑机制的见解，用于评估儿童神经损伤的新型快速非侵入性过程和持续疼痛的预测因子。这些方法可以快速、轻松地整合到临床或临床试验中。

项目成果

DTI and MTR Measures of Nerve Fiber Integrity in Pediatric Patients With Ankle Injury.

• DOI: 10.3389/fped.2021.656843
• 发表时间: 2021
• 期刊: Frontiers in pediatrics
• 影响因子: 2.6
• 作者: Holmes SA;Karapanagou A;Staffa SJ;Zurakowski D;Borra R;Simons LE;Sieberg C;Lebel A;Borsook D
• 通讯作者: Borsook D

Pain stickiness in pediatric complex regional pain syndrome: A role for the nucleus accumbens.

• DOI: 10.1016/j.ynpai.2021.100062
• 发表时间: 2021-01
• 期刊: Neurobiology of pain (Cambridge, Mass.)
• 作者: Youssef AM;Peng K;Kim PK;Lebel A;Sethna NF;Kronman C;Zurakowski D;Borsook D;Simons LE
• 通讯作者: Simons LE

When pain gets stuck: the evolution of pain chronification and treatment resistance.

• DOI: 10.1097/j.pain.0000000000001401
• 发表时间: 2018-12
• 期刊: Pain
• 影响因子: 7.4
• 作者: Borsook D;Youssef AM;Simons L;Elman I;Eccleston C
• 通讯作者: Eccleston C

Biological and behavioral markers of pain following nerve injury in humans.

• DOI: 10.1016/j.ynpai.2019.100038
• 发表时间: 2020-01-01
• 期刊: Neurobiology of pain (Cambridge, Mass.)
• 作者: Holmes, S A;Barakat, N;Borsook, D
• 通讯作者: Borsook, D

Biological laterality and peripheral nerve DTI metrics.

• DOI: 10.1371/journal.pone.0260256
• 发表时间: 2021
• 期刊: PloS one
• 影响因子: 3.7
• 作者: Holmes SA;Staffa SJ;Karapanagou A;Lopez N;Karian V;Borra R;Zurakowski D;Lebel A;Borsook D
• 通讯作者: Borsook D