Evaluating dynamic associations between pain catastrophizing and the effect of cannabinoids

项目摘要 该NRSA F32提案包括一个协调的培训计划和研究项目，将促进 候选人的过渡，成为一个富有成效的，独立的调查员。具体而言，申请人建议 三个培训目标：（1）发展心理物理疼痛评估的专业知识;（2）获得全面的 进行人类行为药理学研究的方法学，安全性和伦理学知识; 以及（3）加深对大麻/大麻素、其作用机制和风险的了解。学到的技能将 将被应用于进行一项研究项目，该项目将研究FDA批准的大麻素 (i.e.,屈大麻酚）与疼痛灾难化动态相关，这是负性疼痛相关的一个有效预测因子。 结果和疼痛管理中的关键心理因素。虽然慢性疼痛是一种 这种影响数百万人的疾病，目前疼痛的治疗选择仍然主要依赖于阿片类药物， 有很大的安全隐患因此，研究更安全和更有效的药理学疼痛 管理战略对公共卫生至关重要。临床前研究表明， 大麻素作为一种有效的止痛剂。然而，关于大麻素镇痛效果的研究结果表明， 在人类临床研究中广泛混合。此外，尽管有效的疼痛 管理涉及解决疼痛减轻以外的各种因素，以前对大麻素的研究 仅将评估疼痛强度作为主要终点。申请人提出， 灾难化（PC），一种对疼痛的适应不良状态和特质认知情感反应，可以发挥重要的作用， 在扩大我们对大麻素在疼痛管理中的潜在效用的初步理解方面发挥了作用。的 拟议的研究建立在申请人的知识和经验，疼痛相关的认知和个人 疼痛调节的差异。本项目将基于申办者的NIH资助的母公司R 01（DA 042751） 这是一项受试者内、随机、双盲和安慰剂对照的人体实验室实验， 慢性疼痛患者申请人提出的研究旨在研究大麻素减少 状态PC和性状PC对大麻素镇痛效果的影响。预计大麻素 施用将导致状态PC比安慰剂更大的降低。也有人假设， 具有较高特征PC的个体相对于具有较低特征PC的个体将表现出显著较低的大麻素镇痛。 特征PC。申请人将从本研究中获得的培训和指导将有助于他 实现他的长期目标，解开疼痛调节的生物行为机制， 个性化的综合疼痛管理方案。此外，本研究将有助于 对大麻素在疼痛管理中的治疗潜力以及精确疼痛的细微评价 这是重要的公共卫生目标。

Project Summary This NRSA F32 proposal includes a coordinated training plan and research project that will facilitate the candidate's transition to becoming a productive, independent investigator. Specifically, the applicant proposes three training goals: (1) develop expertise in psychophysical pain assessment; (2) acquire comprehensive knowledge of the methodology, safety, and ethics of conducting human behavioral pharmacological research; and (3) deepen knowledge of cannabis/cannabinoids, their mechanisms of action, and risk. Learned skills will be applied to conducting a research project that will examine how the effect of an FDA-approved cannabinoid (i.e., dronabinol) is dynamically associated with pain catastrophizing, a potent predictor of negative pain-related outcomes and a crucial psychological factor in pain management. Although chronic pain is a debilitating condition that affects millions of individuals, current treatment options for pain still largely rely on opioids, which have substantial safety concerns. Thus, investigating safer and more effective pharmacological pain management strategies is imperative for public health. Pre-clinical studies suggest considerable promise of cannabinoids as an effective analgesic agent. However, findings on the efficacy of cannabinoid analgesia have been widely mixed across human clinical studies. Furthermore, despite the fact that effective pain management involves addressing various factors beyond pain reduction, previous studies on cannabinoids have only focused on evaluating pain intensity as their primary endpoint. The applicant proposes that pain catastrophizing (PC), a maladaptive state and trait cognitive-affective response to pain, can play an important role in expanding our nascent understanding of cannabinoids’ potential utility in pain management. The proposed study builds upon the applicant’s knowledge and experience in pain-related cognition and individual differences in pain regulation. This project will be based upon sponsors’ NIH-funded parent R01 (DA042751) that is a within-subject, randomized, double-blind, and placebo-controlled human laboratory experiment with chronic pain patients. The applicant’s proposed study aims to investigate cannabinoids’ potential to reduce state PC and the influence of trait PC on analgesic efficacy of cannabinoids. It is expected that cannabinoid administration will result in a greater reduction in state PC than a placebo. It is also hypothesized that individuals with higher trait PC will exhibit significantly lower cannabinoid analgesia relative to those with lower trait PC. The training and mentorship that the applicant will receive from pursing the present study will help him attain his long-term goal of unraveling the bio-behavioral mechanisms of pain regulation and developing personalized integrative pain management programs. Furthermore, the present study will contribute to a nuanced evaluation of cannabinoids’ therapeutic potential in pain management, as well as precision pain medicine, which are important public health goals.