Predicting Post-Operative Pain and Analgesic Use: The Role of Endogenous Opioids

描述（由申请人提供）：该职业发展奖（K23）将为候选人提供必要的培训，以建立与理解关键神经行为风险因素（即不规则中枢疼痛处理，睡眠障碍和消极思维）如何影响神经生物学机制（即内源性阿片功能）相关的研究计划，这些机制导致疼痛结果的个体差异。慢性疼痛是影响很大一部分美国人口的主要健康问题，并与巨大的痛苦和经济负担有关。睡眠障碍、情绪和中枢疼痛加工异常已被确定为慢性疼痛和残疾的重要预测因素，并与内源性阿片功能受损间接相关。拟议的研究计划将系统地解决通过纳洛酮挑战预测膝关节骨性关节炎（OA）患者全膝关节置换术（TKA）后疼痛和阿片类镇痛药使用的内源性阿片类功能的直接术前测试的应用，OA是最常见的慢性疼痛疾病之一，预计随着美国人口老龄化将急剧增加。该K23的具体培训目标包括指导、教学和经验，旨在培养疼痛神经生物学、阿片类药物阻断和睡眠评估方法方面的专业知识，并在生物统计分析方面打下坚实的基础。到目前为止，还没有研究检验中枢性疼痛加工异常、睡眠障碍和情绪与内源性阿片功能受损之间的关系。因此，拟议的研究计划旨在调查这些风险因素是否具有共同的神经生物学基础，将它们与TKA后重要的临床疼痛结果联系起来，包括TKA后持续疼痛和阿片类药物使用增加。特别地，该研究将系统地评估通过纳洛酮刺激对内源性阿片类药物功能的直接术前测试在预测TKA术后疼痛和阿片类药物使用中的有效性。进一步的工作将研究内源性阿片功能是否与中枢疼痛加工异常、睡眠障碍和疼痛相关的疼痛消极思维有关。了解风险因素及其对TKA后预后影响的潜在机制，将对手术患者的选择、术后疼痛的管理、改善慢性疼痛患者的健康相关生活质量，以及帮助制定旨在减少本提案中研究的风险因素影响的干预措施具有重要意义。候选人的长期目标是完善疼痛的生物心理社会模型，促进术后疼痛治疗干预的发展或加强，并预防慢性。

DESCRIPTION (provided by applicant): This Career Development Award (K23) will provide the candidate the necessary training to establish a program of research related to understanding how key neurobehavioral risk factors (i.e., irregular central pain processing, sleep disturbance, and negative thinking) impact neurobiological mechanisms (i.e., endogenous opioid function) that contribute to individual differences in pain outcomes. Chronic pain is a major health problem affecting a significant proportion of the American population and is associated with substantial suffering and economic burden. Sleep disturbance, mood, and aberrant central pain processing have been identified as important predictors of chronic pain and disability, and have been indirectly associated with impaired endogenous opioid function. The proposed research plan will systematically address the utility of a direct pre-surgical test of endogenous opioid function via naloxone challenge in predicting pain and opioid analgesic use following total knee arthroplasty (TKA) in patients with knee osteoarthritis (OA), one of the most prevalent chronic pain conditions and predicted to drastically increase as the U.S. population ages. Specific training aims of this K23 include mentorship, didactics, and experiences designed to develop expertise in the neurobiology of pain, opioid blockade and sleep assessment methods as well as develop a solid foundation in biostatistical analyses. No research to date has examined the relationship between abnormal central pain processing, sleep disturbance, and mood with impaired endogenous opioid function. Consequently, the proposed research plan intends to investigate whether these risk factors share a neurobiological substrate that links them to important clinical pain outcomes following TKA, including persistent post-TKA pain, and increased opioid use. In particular, the proposed study will systematically evaluate the effectiveness of a direct pre- surgical test of endogenous opioid function via naloxone challenge in predicting post-operative pain and opioid use following TKA. Additional work will examine whether endogenous opioid function is associated with abnormal central pain processing, sleep disturbance, and pain related negative thinking on pain. Understanding the risk factors and underlying mechanisms whereby they exert their influence on outcomes following TKA, will have important implications for the selection of surgical patients, inform the management of post-operative pain, improve the health-related quality of life of individuals with chronic pain, and assist in the development of interventions designed to reduce the impact of the risk factors studied in this proposal. The candidate's long term goal is to refine biopsychosocial models of pain and facilitate the development or enhancement of therapeutic interventions for post-operative pain and to prevent chronicity. PUBLIC HEALTH RELEVANCE: Osteoarthritis (OA) affects 20 million older Americans and the prevalence of knee OA is projected to dramatically increase as the U.S. population ages. Pain is the most common symptom associated with degenerative joint disease and is aggravated by abnormal functioning of central pain modulatory systems, sleep disturbance, and negative thinking. The proposed study will increase understanding of the mechanisms by which these factors impact pain related outcomes following total knee arthroplasty (TKA). Findings from this study will be used to alter modifiable risk factors associated with the development of chronic pain and to develop and refine psychosocial interventions for post-operative pain.