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.

National Institute of Health (NIH)
National Institute on Drug Abuse (NIDA)
Exploratory/Developmental Grants (R21)
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Special Emphasis Panel (ZRG1-RPIA-N (09))
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Lin, Yu
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Syracuse University
Schools of Arts and Sciences
United States
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Ditre, Joseph W; Zale, Emily L; LaRowe, Lisa R et al. (2018) Nicotine deprivation increases pain intensity, neurogenic inflammation, and mechanical hyperalgesia among daily tobacco smokers. J Abnorm Psychol 127:578-589
Kosiba, Jesse D; Zale, Emily L; Ditre, Joseph W (2018) Associations between pain intensity and urge to smoke: Testing the role of negative affect and pain catastrophizing. Drug Alcohol Depend 187:100-108
LaRowe, Lisa R; Kosiba, Jesse D; Zale, Emily L et al. (2018) Effects of nicotine deprivation on current pain intensity among daily cigarette smokers. Exp Clin Psychopharmacol 26:448-455
Ditre, Joseph W; Zale, Emily L; Heckman, Bryan W et al. (2017) A measure of perceived pain and tobacco smoking interrelations: pilot validation of the pain and smoking inventory. Cogn Behav Ther 46:339-351
Ditre, Joseph W; Heckman, Bryan W; Zale, Emily L et al. (2016) Acute analgesic effects of nicotine and tobacco in humans: a meta-analysis. Pain 157:1373-81
Zale, Emily L; Maisto, Stephen A; Ditre, Joseph W (2016) Anxiety and Depression in Bidirectional Relations Between Pain and Smoking: Implications for Smoking Cessation. Behav Modif 40:7-28
Ditre, Joseph W; Kosiba, Jesse D; Zale, Emily L et al. (2016) Chronic Pain Status, Nicotine Withdrawal, and Expectancies for Smoking Cessation Among Lighter Smokers. Ann Behav Med 50:427-35
Zale, Emily L; Maisto, Stephen A; Ditre, Joseph W (2015) Interrelations between pain and alcohol: An integrative review. Clin Psychol Rev 37:57-71
Ditre, Joseph W; Langdon, Kirsten J; Kosiba, Jesse D et al. (2015) Relations between pain-related anxiety, tobacco dependence, and barriers to quitting among a community-based sample of daily smokers. Addict Behav 42:130-5
Zale, Emily L; Ditre, Joseph W (2015) Pain-Related Fear, Disability, and the Fear-Avoidance Model of Chronic Pain. Curr Opin Psychol 5:24-30

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