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: 8236910
• 负责人: Jon-Kar Zubieta
• 金额: $ 49.49万
• 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/8236910
• 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; Psychophysiology; 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. PUBLIC HEALTH RELEVANCE: Chronic low back pain and nicotine addiction are frequent co-occurring conditions. These studies will determine the effect of nicotine dependence, persistent low back pain and their interaction on brain neurotransmitter systems that are involved in both the reinforcing effects of nicotine and pain regulation. Neural responses will then be related to the individual pain report and severity of nicotine addiction.

描述（由申请人提供）：已观察到尼古丁依赖和持续性疼痛之间存在高水平的合并症。还有建议认为，尼古丁依赖可能会使经历持续性疼痛的患者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，在神经生物学和表型水平上，尤其是在人类中，人们对尼古丁依赖和慢性疼痛之间相互作用的影响知之甚少。目前的提议涉及慢性疼痛和尼古丁依赖的病理生理学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。建议检查内源性阿片类药物和多巴胺神经传递的功能，这些系统参与尼古丁在中枢神经系统中的增强作用，但也已知在慢性疼痛情况下失调。我们建议首先通过与非吸烟者对照进行比较，来表征尼古丁依赖对多巴胺和阿片类药物系统对持续实验疼痛的反应的影响。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（例如渴望）相关的措施相关。在慢性腰痛患者、尼古丁依赖者或非吸烟者的样本中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]雷氯必利以及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。将量化基线、疼痛预期和疼痛反应，并根据所提议的四个匹配志愿者组的心理物理特征进行检查：非吸烟者和尼古丁依赖者对照、慢性腰痛非吸烟者和尼古丁依赖者。这些研究完成后，我们将能够确定尼古丁依赖如何改变人类的疼痛反应，以及临床和实验上的疼痛如何改变这种成瘾的神经生物学和表型要素（例如，渴望）。此外，现有的持续性疼痛状况与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以及尼古丁依赖的测量相关。尼古丁依赖和慢性疼痛都是具有高度合并症的自我延续性疾病。拟议的研究将阐明它们在神经生物学和心理物理学层面上的相互作用点，为理解患者表现和临床过程的个体差异提供急需的信息。这些信息最终将通过为其发展提供神经生物学框架来指导个体化治疗策略。 公共卫生相关性：慢性腰痛和尼古丁成瘾是常见的并发疾病。这些研究将确定尼古丁依赖、持续性腰痛及其对大脑神经递质系统的相互作用的影响，这些神经递质系统参与尼古丁的增强作用和疼痛调节。然后，神经反应将与个体疼痛报告和尼古丁成瘾的严重程度相关。