Joseph W. Ditre, Ph.D. - US grants

[unreadable] DESCRIPTION (provided by applicant): Project Summary. Chronic pain affects more than 50 million Americans per year and is the third leading cause of physical impairment in the United States, following cancer and heart disease. Tobacco use, particularly cigarette smoking, has an economic impact of over $167 billion annually, harms nearly every organ of the body, and remains the leading preventable cause of death in the United States. The prevalence of smoking among chronic pain patients is approximately double that of the general population. Research suggests that smoking may be a risk factor for the development and exacerbation of chronically painful conditions. However, consistent with evidence of smoking-related analgesia, most patients declare a need to smoke when in pain, and positive correlations between pain intensity and number of cigarettes smoked have been reported. Furthermore, a recent study by the applicant provided the first experimental evidence that situational pain is a potent motivator of smoking. The main goal of the proposed study is to test the causal relationship between pain and smoking motivation by manipulating potential mediating and moderating variables, as influenced by social learning theory-based conceptualizations of pain coping and addiction motivation. A total of 132 smokers will be randomly assigned to one of four conditions in this 2X2 crossed factorial between-subjects design. We hypothesize that, following pain induction, manipulations designed to (1) enhance pain-related coping behaviors, and (2) diminish smoking-related outcome expectancies will each reduce motivation to smoke, when compared to control conditions. We will also test for an interactive, synergistic effect between the two manipulations. The first factor manipulates a variable that the pain literature has shown to predict reduced pain reactivity, whereas the second factor manipulates a variable that has been shown in the smoking literature to influence smoking motivation. Thus, the current proposal draws upon both the pain and smoking literature. Relevance. This experimental design will allow us to test theoretical mechanisms that may underlie and impact the causal relationship between pain and enhanced smoking motivation. This design will also serve as an analogue test of variables that may merit further investigation for their capacity to influence the development of interventions targeted at individuals with comorbid pain and addiction disorders. The ultimate goals of this line of research are to better understand the relationship between smoking and chronic pain, and to develop smoking prevention, cessation, and relapse prevention interventions targeted at individuals who endure chronic pain. [unreadable] [unreadable] [unreadable]

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.

DESCRIPTION (provided by applicant): Tobacco smoking, chronic pain, and prescription analgesic misuse are all highly prevalent among older adults with HIV. The prevalence of smoking among persons with HIV is three times that observed in the general population, and older HIV+ smokers are particularly vulnerable to chronic pain and opioid misuse, in part due to complex nicotine-opioid interactions. Computer-based personalized feedback interventions (PFI) offer great promise as an approach to increasing motivation to quit smoking and reducing medication misuse because they are portable, adaptable, cost-effective, and can be delivered to a large number of patients by non- specialized care providers. Given that the vast majority of all smokers with HIV are not yet ready to quit smoking, research designed to increase motivation and confidence to quit smoking is both novel and consistent with the needs of the target population. The goal of the proposed study is to adapt and pilot test a brief, integrated, computer-based PFI for older adults with comorbid HIV and chronic pain aimed at increasing intentions to quit smoking and decreasing intentions to misuse prescription analgesic medications. Participants will include 76 older tobacco smokers with comorbid HIV and chronic pain, recruited from the Designated AIDS Center at SUNY Upstate Medical University. Participants will be randomized to either Active or Control PFI conditions. The Active PFI will include content relevant to interactions between chronic pain, tobacco smoking, and analgesic medication use/misuse in the context of HIV and aging. The Control PFI will include content relevant to the importance of exercise, nutrition, and medication adherence in the context of HIV and aging. We hypothesize that participants randomized to the Active PFI (relative to Control PFI) will evince: (1) a greater increase in motivation, confidence, and intention to quit smoking; (2); a greater decrease in positive attitudes and intentions toward the misuse of prescription analgesic medications; (3) a greater increase in knowledge regarding interrelations between pain, smoking, and analgesic medication use/misuse in the context of normative aging; and (4) a greater decrease in expectancies regarding the potential benefits of continued smoking and analgesic misuse in the context and course of both chronic pain and HIV. We also hypothesize that decreased positive expectancies for continued smoking and analgesic misuse in the context and course of both chronic pain and HIV will mediate the effects of the proposed intervention on respective smoking and prescription analgesic misuse outcomes. By adapting a brief and portable intervention for older smokers with HIV and chronic pain, our novel intervention strategy addresses a critical public health need in a population that has, to date, been underrepresented in research. We anticipate that a computer-based PFI will function as a first line of defense in HIV care settings, and the proposed study will be the first to target boh smoking and prescription analgesic misuse among older HIV+ individuals.

? DESCRIPTION (provided by applicant): The societal impact of heavy alcohol consumption and chronic pain is substantial and warrants the existing research investment into their etiology and treatment. Moreover, evidence of significant co-occurrence between these conditions offers an opportunity to examine mechanisms in the alcohol-pain connection that may inform the development of novel treatments. Consistent with NIH PA-15-026 (Mechanistic Studies of Pain and Alcohol Dependence), the goal of the proposed study is to examine several complex and potentially bidirectional relations between pain and alcohol in one overarching model, which has never been attempted in a human experimental paradigm. The primary study aims are as follows: (1) to conduct the first test of both pharmacological and expectancy effects in acute alcohol analgesia among humans; (2) to conduct the first test of pain as a proximal antecedent of urge to drink and ad lib alcohol consumption, and to test whether acute analgesic effects predict pain-induced alcohol urge/consumption; (3) to test associations between study outcomes and candidate genetic polymorphisms that have been implicated in pain-alcohol processes; and (4) to conduct exploratory analyses of gender and pain relevant cognitive-affective factors as moderators of these outcomes. Participants will include 280 moderate-to-heavy drinkers recruited from the local community. Experimental methods will include alcohol administration (moderate dose vs. low dose vs. placebo vs. control) and pre/post assessment of static/dynamic pain responses (study visit 1), and capsaicin/heat pain induction (vs. no pain induction) followed by assessment of urge to drink and ad lib alcohol consumption (study visit 2). By employing a novel experimental paradigm, the study results will provide internally valid data with clear and direct implications for translating these findings to clinical applications. Itis our expectation that this work will catalyze future research and inform clinical practice by establishing an experimental platform that allows for the demonstration of causal effects, the evaluation of treatment components prior to conducting costly clinical trials, and the identification of important theory-based biopsychosocial mechanisms that can inform the development of novel integrated treatments for individuals with co-occurring pain and alcohol use disorders.

PROJECT SUMMARY/ABSTRACT Over one-quarter of American adults engage in hazardous drinking (i.e., a pattern of alcohol consumption that increases risk for harmful consequences), which is the third leading cause of preventable death in the U.S. Rates of hazardous drinking are significantly higher among individuals with (vs. without) chronic pain. Moreover, 20% of individuals prescribed opioids endorse concurrent alcohol and opioid use, which may interfere with chronic pain treatment and lead to dangerous/potentially fatal health effects. No interventions to date have targeted either hazardous drinking or concurrent use of alcohol and opioids in the context of chronic pain. The current four-year R01 proposal builds upon our past work by developing a brief, single-session, computer-based, personalized feedback intervention (PFI) designed to enhance knowledge regarding adverse pain-alcohol-opioid interrelations, increase motivation and intention to reduce hazardous drinking, and reduce positive attitudes and intention regarding concurrent use of alcohol and prescription opioid medications. Specifically, we are proposing to develop an integrated PFI for hazardous drinkers with chronic pain who are prescribed opioids (PA-PFI). Our approach will follow a staged model consistent with NIH guidelines for developing and standardizing behavioral interventions. Phase IA activities will involve collecting qualitative and quantitative feedback from three iterative focus groups (N = 21) to refine intervention content and evaluate treatment acceptability and feasibility. Phase IB activities will include a proof-of-concept and highly rigorous randomized clinical trial designed to compare PA-PFI to control PFI (C-PFI) among a sample of 174 hazardous drinkers with chronic pain who are currently prescribed opioid medications. This study represents an important and pivotal step in the larger landscape of translating basic research to more efficacious strategies for reducing hazardous drinking among underserved populations with medical comorbidities. The proposed intervention would be highly disseminable and relevant to millions of hazardous drinkers with chronic pain. Given the collective public health impact of chronic pain, hazardous drinking, and concurrent alcohol-prescription opioid use, we believe the proposed study will yield findings that enhance scientific knowledge, enhance our understanding of mechanisms in reciprocal pain-alcohol-opioid relations, and inform the development of novel treatments for hazardous drinkers with chronic pain that are adaptable and easily implemented across a variety of healthcare settings.