Recovery from Pain and Disability after Surgery

手术后疼痛和残疾的恢复

基本信息

批准号：
10360703
负责人：
James Eisenach
金额：
$ 15.65万
依托单位：
WAKE FOREST UNIVERSITY HEALTH SCIENCES
依托单位国家：
美国
项目类别：
财政年份：
2016
资助国家：
美国
起止时间：
2016-04-01 至 2022-03-31
项目状态：
已结题

项目摘要

Project Summary Surgery benefits most patients, but for some, it results in chronic pain and disability. This is particularly troubling with a surgery which is performed to alleviate pain and disability, such as total knee arthoplasty (TKA). One-two years after TKA, 10-30% of patients have moderate-severe knee pain, 40% fail to show minimal clinically important improvement for function, and 20% are unsure or dissatisfied with surgery. Cognitive style, especially catastrophizing, is an important predictor of these poor outcomes, but how this slows recovery and whether it can be treated are unknown. A critical barrier to progress in this field is the arbitrary and dichotomous definition of the problem and focus on presence or absence of pain or disability at an arbitrary time. This disregards the ongoing recovery process itself and can mislead predictive models and study of mechanisms and treatment. Similarly, few prospective studies of postoperative recovery integrate patient-centered outcomes. To address these gaps we will: Aim 1: Characterize the dynamic pain experience, activity, and cognitive response after TKA and determine patterns of recovery in these domains Another critical barrier to progress in the field is the lack of a, modifiable hypothesis linking C-A state to slowed recovery across multiple patient-centered domains. This P01 tests the hypothesis that tonic locus coeruleus (LC) activity, inferred by pupillometry, interacts with cognitive style along a catastrophizing ↔ optimism (C↔O) continuum to perception of pain and time course of recovery from pain, physical disability, impulsivity, and executive function. Gabapentin, often used to treat chronic pain, activates the LC in animals, but fails to prevent chronic pain after surgery in a general population. We believe this failure reflects opposing actions of LC activity depending on baseline C↔O style, and in our second aim will: Aim 2: Test whether gabapentin alters time course of recovery after TKA in a manner dependent on its interaction with pre-drug pupil diameter and preferred style in the C↔O dimension Finally, as a first step to eventually test whether gabapentin responders can also be identified in patients on high dose opioids (who are at high risk for pain after surgery) we will: Aim 3: Test whether gabapentin increases pupil diameter in patients undergoing TKA who are on high dose opioids preoperatively and to examine whether opioid use moderates the associations in Aim 1 This administrative supplement will allow completion of the clinical trial for Aims 1 and 2 which was delayed in starting due to unforeseen circumstances and then delayed in 2020 due to the pandemic. Without the modest supplement, the trial will not achieve enrollment as designed to have adequate power to test the underlying hypotheses.

项目概要手术对大多数患者有益，但对某些患者来说，它会导致慢性疼痛和残疾。为减轻疼痛和残疾而进行的手术（例如全膝关节置换术）遇到麻烦 (TKA) TKA 后一到两年，10-30% 的患者出现中度至重度膝关节疼痛，40% 没有表现出来。临床上重要的功能改善微乎其微，20% 对手术不确定或不满意。认知风格，尤其是灾难化认知风格，是这些不良结果的重要预测因素，但如何做到这一点？恢复速度减慢，是否可以治疗尚不清楚。该领域取得进展的一个关键障碍是对问题和问题的任意和二分法定义。关注任意时间是否存在疼痛或残疾，这忽略了正在进行的恢复。过程本身，可能会误导预测模型以及机制和治疗的研究。，类似地术后恢复的前瞻性研究整合了以患者为中心的结果，为了解决这些差距，我们。将要：目标 1：描述 TKA 和术后动态疼痛体验、活动和认知反应的特征确定这些领域的恢复模式该领域取得进展的另一个关键障碍是缺乏将 C-A 状态与该 P01 测试了强直基因座的假设。通过瞳孔测量推断的蓝斑 (LC) 活动与认知风格沿着灾难性 ↔ 相互作用乐观（C↔O）是对疼痛的感知以及从疼痛、身体残疾、加巴喷丁常用于治疗慢性疼痛，可激活动物的 LC，但未能预防普通人群手术后的慢性疼痛，我们认为这种失败反映了反对意见。 LC 活动的行为取决于基线 C↔O 风格，我们的第二个目标将：目标 2：测试加巴喷丁是否会改变 TKA 后恢复的时间进程，其方式取决于其与用药前瞳孔直径和 C↔O 维度中首选风格的相互作用最后，作为最终测试加巴喷丁反应者是否也可以在服用高剂量阿片类药物的患者（术后疼痛风险较高）我们将：目标 3：测试加巴喷丁是否会增加接受 TKA 的高视力患者的瞳孔直径术前服用阿片类药物，并检查阿片类药物的使用是否会缓和目标 1 中的关联该行政补充将允许完成目标 1 和 2 的临床试验由于不可预见的情况推迟了启动，然后由于大流行而推迟了2020年。适度的补充，试验将无法达到设计时的入组目的，有足够的能力来测试基本假设。

项目成果

期刊论文数量（16）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Nerve injury induced activation of fast-conducting high threshold mechanoreceptors predicts non-reflexive pain related behavior.

神经损伤诱导的快速传导高阈值机械感受器的激活可预测非反射性疼痛相关行为。

DOI：
发表时间：
2016-10-06
期刊：
影响因子：
2.5
作者：
Boada, M Danilo;Martin, Thomas J;Ririe, Douglas G
通讯作者：
Ririe, Douglas G

Incisional Nociceptive Input Impairs Attention-related Behavior and Is Associated with Reduced Neuronal Activity in the Prefrontal Cortex in Rats.

切口伤害性输入损害注意力相关行为，并与大鼠前额皮质神经元活动减少有关。

DOI：
发表时间：
2018
期刊：
影响因子：
8.8
作者：
Ririe, Douglas G;Boada, M Danilo;MacGregor, Megan K;Martin, Salem J;Strassburg, Tracy J;Kim, Susy A;Eisenach, James C;Martin, Thomas J
通讯作者：
Martin, Thomas J

Factors mediating pain-related risk for opioid use disorder.

介导阿片类药物使用障碍疼痛相关风险的因素。