Effect of Alcohol Withdrawal on Pain Sensitization

戒酒对疼痛敏化的影响

• 批准号: 8909556
• 负责人: Dokyoung Sophia You
• 金额: $ 3.22万
• 依托单位: TEXAS A&M UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-06-01 至 2017-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8909556
• 关键词: Absence of pain sensation; Abstinence; Acute; Affect; Affective; Alcohol abuse; Alcohol consumption; Alcohol dependence; Alcohol withdrawal syndrome; Alcoholic Intoxication; Alcohols; Analgesics; Animal Model; Animals; Anxiety; Capsaicin; Circadian Rhythms; Clinical; Cutaneous Muscle; Dependence; Development; Dose; Epinephrine; Ethics; Exhibits; Experimental Models; Future; Genetic; Goals; Health; Heating; Heavy Drinking; Hormones; Hour; Human; Hydrocortisone; Hyperalgesia; Individual; Laboratories; Link; Maintenance; Measures; Mechanics; Mediating; Mental Depression; Modeling; Neuropathy; Nociceptors; Pain; Pain Disorder; Pain Threshold; Participant; Pathway interactions; Patient Self-Report; Patients; Pattern; Peripheral; Peripheral Nervous System Diseases; Physiological; Plasma; Play; Preventive; Primary Hyperalgesias; Psychological Stress; Rattus; Reporting; Research; Role; Secondary Hyperalgesias; Signal Transduction; Societies; Staging; Stress; Symptoms; System; Testing; Therapeutic; Time; Translating; Withdrawal; Withdrawal Symptom; age group; alcohol sensitivity; anxiety states; binge drinker; binge drinking; biological adaptation to stress; central pain; central sensitization; chronic neuropathic pain; chronic pain; drinking; effective therapy; hangover; insight; middle age; negative emotional state; new therapeutic target; painful neuropathy; peripheral pain; pressure; prevent; protein kinase C epsilon; psychologic; public health relevance; research study; response; sobriety; trait; young adult

 DESCRIPTION (provided by applicant): Excessive alcohol consumption often precedes the development of chronic pain. Subjective symptoms of neuropathy are reported to emerge after relatively short periods of excessive drinking in some binge drinkers. In animal models of binge drinking, excessive alcohol consumption increases pain sensitivity during alcohol withdrawal, and this hyperalgesia transitions to painful cutaneous and muscle neuropathy within three weeks. Importantly, these changes in pain sensitivity are mediated by the release of stress hormones, which in turn alter protein kinase C epsilon (PKCe) signaling in nociceptors. Because these findings have potential implications for understanding the mechanisms underlying the association between alcohol abuse and pain conditions, human studies are warranted to determine the generality of the phenomenon and mechanisms of alcohol withdrawal- induced hyperalgesia. To date no human research has examined the effects of alcohol withdrawal on pain sensitivity [in early stages of binge drinking.] Such a study could determine whether alcohol sensitizes pain pathways well before the development of irreversible chronic neuropathic pain. Thus, the proposed study will investigate the effects of binge drinking on sensitization of pain in young adults to determine, first, whether binge drinkers' basal pain sensitivity is enhanced in comparison to the controls (i.e., moderate alcohol users and abstainers), and further intensified during alcohol withdrawal. Second, the proposed study examines whether this hyperalgesia is associated with elevated circulating levels of epinephrine and cortisol. The role of negative affect in alcohol withdrawal-induced hyperalgesia will also be explored because it is linked to enhanced physiological stress responses and pain sensitivity in humans. Experiment 1 is modeled after prior animal studies and will examine whether binge drinking alters peripheral pain sensitization (i.e., heat pain thresholds, mechanical hyperalgesia, and pressure pain). Experiment 2 will use a laboratory model of neuropathic pain, the topical capsaicin test, to induce primary and secondary hyperalgesia, which reflects central pain sensitization. Binge drinkers who have consumed alcohol within 48 hours prior to the experiment are hypothesized to show enhanced peripheral and central pain sensitization compared to those who have not, and to the controls. In addition, circulating levels of epinephrine and cortisol are expected to mediate alcohol withdrawal-induced hyperalgesia. Finally, negative affect is expected to be associated with enhanced alcohol withdrawal hyperalgesia. The results of this study will determine whether the mechanisms underlying alcohol withdrawal-induced hyperalgesia and neuropathy observed in animal models of binge drinking translate to human binge drinkers, and may suggest stress reduction as a new therapeutic target to prevent and treat alcohol neuropathy. Using this experimental model, future studies could investigate the contribution of genetic mechanisms associated with enhanced sensitivity to alcohol analgesia, alcohol withdrawal-induced hyperalgesia, and peripheral neuropathy.