Effects of Smoking Abstinence on Pain Reactivity: A Human Experimental Model

描述（由申请人提供）：烟草依赖和慢性疼痛是两种高度流行的共病疾病，对个人和系统造成巨大负担。疼痛已被证明是吸烟的动机，疼痛患者支持吸烟以应对疼痛，复发性疼痛可能是戒烟的重要障碍。尽管动物研究一直表明尼古丁剥夺会增加疼痛，但我们不知道有任何研究测试戒烟或尼古丁戒断是否会增加人类的疼痛反应。考虑到戒烟后疼痛增加的临床意义，人体试验显然是必要的。因此，拟议研究的主要目标是通过实验测试戒烟对尼古丁依赖性吸烟者自我报告和生理疼痛反应的影响。参与者（N = 198）将在经历疼痛诱导之前被随机分配到三种实验条件之一：（1）24小时戒烟（SA）;（2）两小时最小剥夺（MD）;和（3）继续吸烟（CS）。具体而言，我们假设随机分配到SA条件的吸烟者在实验性疼痛诱导期间将报告比随机分配到MD条件的吸烟者更低的疼痛阈值、更大的疼痛强度和更大的疼痛不愉快，而MD条件的吸烟者反过来将报告比随机分配到CS条件的吸烟者更低的疼痛阈值、更大的疼痛强度和更大的疼痛相关的不愉快（即，SA > MD > CS）。我们还假设尼古丁戒断的特征性症状将介导戒烟和疼痛反应之间的关系，因此戒断严重程度将与疼痛反应增加呈正相关。拟议研究的第二个目的是探索可能介导或缓和戒烟对疼痛反应影响的其他机制的影响。我们将目前提出的研究概念化为翻译，跨学科研究的典型例子，有可能为有针对性的干预措施的发展提供信息。我们还相信，拟议的项目将产生的结果，提高医学和行为科学的科学知识，告知临床实践方面的疼痛和吸烟的治疗，并挑战目前的临床实践范式。例如，有证据表明，疼痛是吸烟的动机，戒烟干预与共病疼痛障碍的人可能会修改，以解释戒烟引起的疼痛放大的对立影响。最后，目前缺乏一个人类实验室模型的疼痛和吸烟，允许操纵吸烟和疼痛代表了一个关键的障碍，在这个广泛的领域的进展。 公共卫生相关性：吸烟在慢性疼痛的发病中起着因果作用，据估计，疼痛患者中吸烟的流行率是一般人群中观察到的两倍，有理由相信戒烟可能会增加疼痛。这项研究的主要目的是操纵戒烟，以确定尼古丁剥夺和随后的戒断效应是否会增加尼古丁依赖吸烟者的疼痛反应。增加的疼痛作为戒烟的功能将破坏疼痛和烟草依赖干预的目标，我们相信，拟议的项目将产生的结果，告知临床实践方面的疼痛和吸烟的治疗。

DESCRIPTION (provided by applicant): Tobacco dependence and chronic pain are two highly prevalent and comorbid conditions that engender substantial burdens upon individuals and systems. Pain has been shown to motivate smoking, pain patients endorse smoking for pain-coping, and recurring pain may serve as a significant barrier to smoking cessation. Although animal studies have consistently demonstrated increased pain in the context of nicotine deprivation, we are not aware of any studies that tested whether smoking abstinence or nicotine withdrawal may increase pain reactivity in humans. Given the clinical implications of experiencing increased pain as a consequence of abstaining from tobacco, human trials are clearly warranted. Therefore, the main goal of the proposed study is to test, experimentally, the effects of smoking abstinence on self-reported and physiological pain responding among nicotine-dependent tobacco smokers. Participants (N = 198) will be randomized to one of three experimental conditions prior to undergoing pain induction: (1) 24-hour smoking abstinence (SA); (2) two-hour minimal deprivation (MD); and (3) continued smoking (CS). Specifically, we hypothesize that smokers randomized to the SA condition will report lower pain threshold, greater pain intensity, and greater pain unpleasantness during experimental pain induction than smokers randomized to the MD condition, who will, in turn, report lower pain threshold, greater pain intensity, and greater pain-related unpleasantness than smokers randomized to the CS condition (i.e., SA > MD > CS). We also hypothesize that symptoms characteristic of nicotine withdrawal will mediate the relationship between smoking abstinence and pain responding, such that withdrawal severity will be positively associated with increased pain responding. A secondary aim of the proposed study is to explore the influence of additional mechanisms that may mediate or moderate the effect of smoking abstinence on pain responding. We conceptualize the currently proposed study as a prototypical example of translational, cross-disciplinary research that has the potential to inform the development of targeted interventions. We also believe the proposed project will yield findings that enhance scientific knowledge within the medical and behavioral sciences, inform clinical practice with regard to the treatment of both pain and smoking, and challenge current clinical practice paradigms. For example, given evidence that pain is a motivator of smoking, smoking cessation interventions for persons with comorbid pain disorders may be modified to account for the antithetical influence of smoking abstinence-induced amplification of pain. Finally, the current lack of a human laboratory model of pain and smoking that allows for manipulation of both smoking and pain represents a critical barrier to progress in this broad domain. PUBLIC HEALTH RELEVANCE: smoking plays a causal role in the onset of chronic pain, the prevalence of smoking among persons in pain is estimated to be twice that observed in the general population, and there is reason to believe that abstaining from smoking may increase pain. The main goal of the proposed study is to manipulate smoking abstinence to determine whether nicotine deprivation and subsequent withdrawal effects may increase pain reactivity among nicotine-dependent smokers. Increased pain as a function of smoking abstinence would undermine the goals of both pain and tobacco dependence interventions, and we believe the proposed project will yield findings that inform clinical practice with regard to the treatment of both pain and smoking.