Evaluating dynamic associations between pain catastrophizing and the effect of cannabinoids

项目摘要 此NRSA F32提案包括一个协调的培训计划和研究项目，将促进 候选人转变为一名富有成效的独立调查员。具体来说，申请人提出了 三个培训目标：(1)发展心理物理疼痛评估方面的专门知识；(2)获得全面的 了解进行人类行为药理学研究的方法学、安全性和伦理学； 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，该项目将检验FDA批准的大麻素的影响 (例如，屈诺比诺)与疼痛灾变动态相关，这是负性疼痛相关的有效预测因子 结果和一个关键的心理因素在疼痛管理。尽管慢性疼痛是一种衰弱的 尽管目前疼痛的治疗方案在很大程度上仍然依赖阿片类药物，但这种疾病影响着数百万人。 有很大的安全顾虑。因此，研究更安全、更有效的药理疼痛 管理策略对公共卫生来说势在必行。临床前研究表明很有希望 大麻素是一种有效的止痛剂。然而，关于大麻素止痛效果的研究结果 在人类临床研究中被广泛混合。此外，尽管有效的疼痛 管理涉及到解决除止痛以外的各种因素，以前对大麻类药物的研究 只专注于评估疼痛强度作为主要终点。申请人提出痛苦的建议 灾难(PC)，一种不适应状态和对疼痛的认知-情感反应，可以发挥重要作用 在扩大我们对大麻素在疼痛治疗中的潜在效用的初步了解方面发挥了重要作用。这个 建议的研究建立在申请者对疼痛相关认知和个人的知识和经验的基础上 疼痛调节方面的差异。该项目将基于赞助商的NIH资助的母公司R01(DA042751) 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。申请人提议的研究旨在调查大麻类物质是否有可能降低 状态PC及特征PC对大麻素镇痛效果的影响。预计大麻素 与安慰剂相比，政府将导致州PC的更大幅度的减少。它还假设 具有较高特质PC的个体将比具有较低特质PC的个体表现出显著较低的大麻素止痛 特征PC。申请人在完成本研究过程中所接受的培训和指导将对他有所帮助。 实现他的长期目标，即解开疼痛调节和发展的生物行为机制 个性化的综合性疼痛管理计划。此外，本研究将有助于 大麻类药物在疼痛管理以及精确疼痛中的治疗潜力的细微差别评估 医学，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.