Interaction of Smoking and Chronic Pain at Neurochemical and Phenotypic Levels

吸烟与慢性疼痛在神经化学和表型水平上的相互作用

• 批准号: 8423407
• 负责人: Jon-Kar Zubieta
• 金额: $ 47.48万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-09-30 至 2015-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8423407
• 关键词: Acute; Address; Affect; Affective; Brain; Characteristics; Chronic low back pain; Cigarette; Clinical; Comorbidity; Control Groups; Cotinine; Data; Dependence; Development; Disease; Dopamine; Drug Addiction; Drug abuse; Elements; Epidemiology; Functional disorder; Human; Imaging Techniques; Incidence; Individual; Intervention; Laboratories; Linear Models; Low Back Pain; Measures; Mediating; Morbidity - disease rate; Neurobiology; Neurophysiology - biologic function; Neurotransmitters; Nicotine; Nicotine Dependence; Nicotine Withdrawal; Opioid; Opioid Receptor; Outcome; Pain; Patient Self-Report; Patients; Persistent pain; Physiological; Plasma; Positron-Emission Tomography; Process; Psychophysics; Raclopride; Regulation; Reporting; Sampling; Severities; Site; Smoking; Stimulus; Stress; Suggestion; System; Variant; Volunteer Group; Work; addiction; biological adaptation to stress; carfentanil; chronic pain; craving; design; endogenous opioids; expectation; experience; human subject; improved; interest; molecular imaging; negative emotional state; neural circuit; neurochemistry; neurotransmission; nicotine craving; non-smoker; public health relevance; radiotracer; relating to nervous system; research study; response; smoking prevalence; stressor; treatment strategy; volunteer

DESCRIPTION (provided by applicant): High levels of comorbidity have been observed between nicotine dependence and persistent pain conditions. There are also suggestions that nicotine dependence may complicate the presentation and outcomes of patients experiencing persistent pain, already a condition that is both difficult to treat and can be self- perpetuating. Experimental evidence shows that nicotine has effects on pain regulatory mechanisms. The effects of the interaction between nicotine dependence and chronic pain are however poorly understood at both neurobiological and phenotypic levels, particularly in humans. The present proposal is concerned with individual variations in the function of neurochemical mechanisms implicated in the pathophysiology of both chronic pain and nicotine dependence and how they impact on the individual characteristics of both disorders. It is proposed to examine the function of endogenous opioid and dopamine neurotransmission, systems involved in the reinforcing effects of nicotine in the CNS, but also known to be dysregulated in chronic pain conditions. We propose to first characterize the effects of nicotine dependence on the responses of dopamine and opioid systems to sustained experimental pain, by comparing them to those of non-smoker controls. Neurobiological responses will then be related to pain psychophysics and measures related to nicotine dependence (e.g., craving). Similar studies and analyses are proposed in samples of chronic low back pain patients, nicotine dependent or non-smokers. We will employ the selective radiotracers [11C]carfentanil and [11C]raclopride and positron emission tomography for the non-invasive quantification of dopamine D2/3 and 5- opioid receptors. Baseline, pain expectation and pain responses will be quantified and examined against psychophysical characteristics across the four matched volunteer groups proposed: non-smoker and nicotine dependent controls, chronic low back pain non-smokers and nicotine dependent. At the completion of these studies we will be able to determine how nicotine dependence modifies pain responses in humans, and how pain, both clinical and experimental, modifies neurobiological and phenotypic elements of this addiction (e.g., craving). In addition, the interaction between an existing persistent painful condition and nicotine dependence will be examined at the neural function level and related to the individual clinical and experimental pain experience and measures of nicotine dependence. Both nicotine dependence and chronic pain are self- perpetuating conditions with high comorbidity. The studies proposed will clarify their points of interaction at neurobiological and psychophysical levels, providing much needed information for the understanding of individual variations in patient presentation and clinical courses. This information would ultimately guide individualized treatment strategies by providing a neurobiological framework for their development.

描述（由申请人提供）：在尼古丁依赖和持续疼痛状况之间观察到高水平的共病。也有人认为，尼古丁依赖可能会使患者持续疼痛的表现和结果复杂化，这种情况既难以治疗，又可能自我延续。实验证据表明，尼古丁对疼痛调节机制有影响。然而，尼古丁依赖和慢性疼痛之间相互作用的影响在神经生物学和表型水平上都知之甚少，特别是在人类中。本研究关注慢性疼痛和尼古丁依赖的病理生理中涉及的神经化学机制功能的个体差异，以及它们如何影响这两种疾病的个体特征。我们建议研究内源性阿片样物质和多巴胺神经传递的功能，这两个系统参与尼古丁在中枢神经系统中的强化作用，但也已知在慢性疼痛条件下失调。我们建议首先描述尼古丁依赖对多巴胺和阿片系统对持续实验性疼痛的反应的影响，通过将它们与非吸烟者对照进行比较。然后，神经生物学反应将与疼痛心理物理学和与尼古丁依赖相关的措施（例如，渴望）相关联。在慢性腰痛患者、尼古丁依赖者或非吸烟者的样本中也提出了类似的研究和分析。我们将采用选择性放射性示踪剂[11C]卡芬太尼和[11C]雷氯pride和正电子发射断层扫描对多巴胺D2/3和5-阿片受体进行无创定量。基线、疼痛预期和疼痛反应将被量化，并对照四组志愿者的心理物理特征进行检查：非吸烟者和尼古丁依赖组，慢性腰痛非吸烟者和尼古丁依赖组。在完成这些研究后，我们将能够确定尼古丁依赖如何改变人类的疼痛反应，以及临床和实验的疼痛如何改变这种成瘾的神经生物学和表型因素（例如，渴望）。此外，存在的持续性疼痛状况和尼古丁依赖之间的相互作用将在神经功能水平上进行检查，并与个体临床和实验疼痛经历和尼古丁依赖的测量有关。尼古丁依赖和慢性疼痛都是自我延续的疾病，具有很高的合并症。提出的研究将阐明它们在神经生物学和心理物理学水平上的相互作用点，为理解患者表现和临床过程的个体差异提供急需的信息。这些信息将最终通过为他们的发展提供一个神经生物学框架来指导个性化的治疗策略。