Abstract and Introduction
Aims: Rodent studies propose potential mechanisms linking excessive drinking and pain hypersensitivity (hyperalgesia), such that stress hormones (i.e. epinephrine and cortisol) mediate induction and maintenance of alcohol withdrawal-induced hyperalgesia. The first aim of this study was to examine whether hyperalgesia would occur within 48 h after a drinking episode in healthy young adult binge drinkers. The second was to examine whether stress hormones and negative effect would be associated with binge drinking or alcohol withdrawal-associated hyperalgesia.
Methods: A cross-sectional experiment was conducted in five groups with naturally occurring drinking (mean age = 19.6, range 18–29 years): abstainers (n = 43, 54% female), moderate drinkers with (n = 50, 50% female) or without recent drinking (i.e. within 48 h, n = 23, 26% female) and binge drinkers with (n = 36, 58% female) or without recent drinking (n = 25, 44% female). All types of drinkers endorsed drinking about 2–3 times a month and 2–3 years of drinking history.
Results: Muscle pressure pain thresholds were significantly lower in the binge group with recent drinking compared to other groups, but cutaneous mechanical and heat pain thresholds were not significantly different across the five groups. Basal epinephrine levels were significantly higher in binge groups regardless of recent drinking, but cortisol and negative effect were not significantly different across the five groups.
Conclusions: This is the first study to show that alcohol withdrawal-associated muscle hyperalgesia may occur in healthy episodic binge drinkers with only 2–3 years of drinking history, and epinephrine may play a role in binge drinking-associated hyperalgesia.
Up to 35% of young adults report binge drinking, a significant health risk behavior (Substance Abuse and Mental Health Services Administration, 2019). Binge drinking is defined as consuming at least 4(women)/5(men) standard drinks within 2 h (National Institute on Alcohol Abuse and Alcoholism, 2004), which increases blood alcohol concentrations (BAC) to 0.08 g% and often causes blackouts (Hingson et al., 2016) and neurotoxicity (Alfonso-Loeches et al., 2013). Following binge drinking, unpleasant physical, neurocognitive and psychological symptoms develop and persist several hours after BAC returns to 0 g% (Swift and Davidson, 1998). These alcohol withdrawal symptoms, commonly called hangover symptoms in the context of young adults' binge drinking, disappear within 2 days (Sellers, 1988).
Rodent studies show that pain hypersensitivity (hyperalgesia) occurs during alcohol withdrawal. This hyperalgesia during withdrawal may explain the relationship between excessive drinking and pain. Reviews, largely based on rodent research, highlight the disrupted stress system as a possible mechanism linking alcohol to pain (Egli et al., 2012; Edwards et al., 2020; Robins et al., 2019). Repeated exposure to alcohol intoxication and withdrawal episodes enhances stress signaling and leads to hyperalgesia. Rats show analgesic responses after an ethanol diet, followed by hyperalgesic responses during alcohol withdrawal (Gatch and Lal, 1999). A study also shows that rats develop hyperalgesia to muscle pressure pain during withdrawal after 1 cycle of an ethanol binge diet, and this hyperalgesia worsens with repeated binges up to 4 cycles (Dina et al., 2006). Surprisingly, rats on a continuous ethanol diet do not develop hyperalgesia, highlighting the role of 'withdrawal', not excessive drinking, in the development of hyperalgesia. Rodent studies have also identified several mechanisms driving the development of alcohol withdrawal-induced hyperalgesia, including increased circulating levels of stress hormones (epinephrine and glucocorticoids, Dina et al., 2008). Blocking the secretion and action of epinephrine or cortisol reverses already occurring hyperalgesia and prevents the occurrence of withdrawal-induced hyperalgesia despite continued cycles of binge and withdrawal (Dina et al., 2008).
Alcohol withdrawal-induced hyperalgesia has received limited attention in the human literature. One human study demonstrated evidence of alcohol withdrawal-associated hyperalgesia in which middle-aged men with alcohol dependence without neuropathy showed reversible pain hypersensitivity during alcohol detoxification (Jochum et al., 2010). This study demonstrated that withdrawal-associated hyperalgesia occurs before the development of alcoholic neuropathic pain. However, it is unknown whether withdrawal-associated hyperalgesia would occur even before the development of alcohol dependence such as in episodic binge drinkers and whether stress hormones are similarly implicated in alcohol withdrawal-associated hyperalgesia of humans. If so, lowering stress hormones by psychological and pharmacological intervention might provide a preventative approach for binge drinkers who are at risk for transitioning from episodic binge drinking to alcohol dependence (e.g. family history of alcoholism, childhood adversity, Fenton et al., 2013) and alcoholic neuropathic pain (e.g. female, Ammendola et al., 2000). Without these preventive approaches, recurrent alcohol intoxication and withdrawal episodes may lead to dysregulation of brain reward and stress systems during the development of alcohol dependence (Egli et al., 2012). Over time, negative effect and persistent pain may play key roles in continued drinking because alcohol provides immediate relief from them, which persist and worsen during alcohol withdrawal (Egli et al., 2012). Eventually, in advanced stages of drinking, irreversible and painful alcoholic neuropathy may develop.
The primary aim of this study was to investigate whether alcohol withdrawal-associated hyperalgesia would occur in healthy young adult binge drinkers. Second, we examined whether measures of psychological and physiological stress would be elevated in binge drinkers who drank alcohol within 2 days. To achieve these aims, we conducted a cross-sectional study to evaluate pain sensitivity after naturally occurring alcohol use. We hypothesized that binge drinkers who drank alcohol within 2 days would show (a) pain hypersensitivity and (b) elevated psychological (negative effect) and physiological (stress hormones) stress levels compared to binge drinkers who did not drink within 2 days, moderate drinkers and abstainers.
Alcohol Alcohol. 2020;55(6):608-615. © 2020 Oxford University Press
Copyright 2007 Medical Council on Alcohol. Published by Oxford University Press. All rights reserved.