Mechanisms of Alcohol Withdrawal-Induced Hyperalgesia in Young Adults

Binge drinking is one of the most dangerous types of alcohol consumption; over 38% of young adults and 24% of adults 26 years of age and older report binge drinking. Motivation to binge drink may come from comorbidity with pain conditions. Considerable animal evidence shows a biphasic relationship between alcohol and pain with intoxication-induced hypoalgesia (decreased sensitivity to painful stimuli) followed by withdrawal-induced hyperalgesia (increased sensitivity to painful stimuli). The anti-reward model of addiction suggests rewarding aspects of intoxication (e.g., analgesia) drive initial consumption. As drinking continues, anti-reward withdrawal aspects (e.g., hyperalgesia) activate brain stress axes and motivate craving and consumption. Following withdrawal, the third phase is anticipation of alcohol. Animal models of alcohol withdrawal-induced muscle mechanical hyperalgesia suggest the hyperalgesia results from changes in peripheral nociceptors mediated by increased release of stress hormones. Consistent with these findings, our laboratory recently observed withdrawal-induced muscle mechanical hyperalgesia and increased circulating levels of epinephrine in young adult binge drinkers using a between-subjects design. The current study used a mixed between-within-subjects design to assess muscle mechanical sensitivity, cutaneous thermal sensitivity, and neurogenic inflammation, as well as a measure of central sensitization of pain — thermal temporal summation of second pain. Blood was collected to investigate moderation by epinephrine and pro-inflammatory IL-6. Individuals were prescreened for alcohol use and categorized as moderate and binge drinkers using National Institute on Alcohol Abuse and Alcoholism (NIAAA) binge drinking criteria. Participants made two visits: one during abstinence (no alcohol within previous 48 hours) and one during withdrawal (drinking within previous 48 hours). We found binge drinkers reported more alcohol use before the withdrawal state, greater hangover symptoms, and more alcohol use disorder symptoms. Importantly, we found that participants in the withdrawal state reported mechanical hyperalgesia in skeletal muscle, partially supporting previous results in animals and our laboratory. In parallel, we found participants in withdrawal reported reduced cutaneous thermal sensitivity on multiple measures. Pain sensitivity results were predominantly driven by effects in male participants. Participants in withdrawal also reported more dominance and less anxiety and negative affect but exhibited greater psychophysiological responses. Several hypotheses for future research are presented

Mechanisms of Alcohol Withdrawal-Induced Hyperalgesia in Young Adults

Binge drinking is one of the most dangerous types of alcohol consumption; over 38% of young adults and 24% of adults 26 years of age and older report binge drinking. Motivation to binge drink may come from comorbidity with pain conditions. Considerable animal evidence shows a biphasic relationship between alcohol and pain with intoxication-induced hypoalgesia (decreased sensitivity to painful stimuli) followed by withdrawal-induced hyperalgesia (increased sensitivity to painful stimuli). The anti-reward model of addiction suggests rewarding aspects of intoxication (e.g., analgesia) drive initial consumption. As drinking continues, anti-reward withdrawal aspects (e.g., hyperalgesia) activate brain stress axes and motivate craving and consumption. Following withdrawal, the third phase is anticipation of alcohol. Animal models of alcohol withdrawal-induced muscle mechanical hyperalgesia suggest the hyperalgesia results from changes in peripheral nociceptors mediated by increased release of stress hormones. Consistent with these findings, our laboratory recently observed withdrawal-induced muscle mechanical hyperalgesia and increased circulating levels of epinephrine in young adult binge drinkers using a between-subjects design. The current study used a mixed between-within-subjects design to assess muscle mechanical sensitivity, cutaneous thermal sensitivity, and neurogenic inflammation, as well as a measure of central sensitization of pain — thermal temporal summation of second pain. Blood was collected to investigate moderation by epinephrine and pro-inflammatory IL-6. Individuals were prescreened for alcohol use and categorized as moderate and binge drinkers using National Institute on Alcohol Abuse and Alcoholism (NIAAA) binge drinking criteria. Participants made two visits: one during abstinence (no alcohol within previous 48 hours) and one during withdrawal (drinking within previous 48 hours). We found binge drinkers reported more alcohol use before the withdrawal state, greater hangover symptoms, and more alcohol use disorder symptoms. Importantly, we found that participants in the withdrawal state reported mechanical hyperalgesia in skeletal muscle, partially supporting previous results in animals and our laboratory. In parallel, we found participants in withdrawal reported reduced cutaneous thermal sensitivity on multiple measures. Pain sensitivity results were predominantly driven by effects in male participants. Participants in withdrawal also reported more dominance and less anxiety and negative affect but exhibited greater psychophysiological responses. Several hypotheses for future research are presented