Hyperalgesia After a Drinking Episode in Young Adult Binge Drinkers

A Cross-Sectional Study

Dokyoung S. You; Hunter A. Hahn; Thomas H. Welsh Jr.; Mary W. Meagher


Alcohol Alcohol. 2020;55(6):608-615. 

In This Article


This study was the first to examine whether hyperalgesia would occur within 2 days of drinking in young adult episodic binge drinkers. We also examined whether this hyperalgesia would be associated with epinephrine and cortisol hormones or negative effect. Our results indicated that hypersensitivity to muscle pressure pain occurred in episodic binge drinkers who reported drinking within 2 days and experiencing acute alcohol withdrawal symptoms at the time of testing. Specifically, PPTs were lower in binge drinkers with recent drinking compared to binge drinkers without it. Therefore, hyperalgesia may occur in episodic binge drinkers during withdrawal. Hypersensitivity to muscle pressure pain was also observed in episodic binge drinkers without recent drinking compared to the moderate drinkers without recent drinking. Yet, binge drinking was not associated with persistent hyperalgesia, as muscle pressure thresholds were not significantly different between abstainers and binge drinkers without recent drinking. Cutaneous mechanical and heat pain thresholds were not associated with binge drinking and alcohol withdrawal. Next, binge drinking was associated with an elevation of plasma epinephrine concentration, but alcohol withdrawal was not associated with its further elevation. In contrast, plasma cortisol concentrations were unrelated to binge drinking and alcohol withdrawal. Finally, we did not find significant group differences in psychological distress levels with one exception. Binge and moderate drinkers reported more depressive symptoms compared to abstainers, suggesting depressive symptoms were associated with alcohol use.

We found that alcohol withdrawal was associated with transitory hypersensitivity to muscle pressure pain, consistent with findings in rodents (Gatch and Lal, 1999; Dina et al., 2000, Dina et al., 2006, Dina et al., 2008;). Our finding is also consistent with previous human research showing reversible withdrawal-associated hyperalgesia in alcohol-dependent men (Jochum et al., 2010). This study extends that work by showing that hypersensitivity to muscle pressure pain may occur during alcohol withdrawal periods even in healthy young adults with only 2–3 years of episodic binge drinking history. With persistent binge drinking, persistent hyperalgesia may develop (Chopra and Tiwari, 2012) as subjective symptoms of alcoholic neuropathy are reported by 20% of alcoholics during the first 5 years of misuse and 40% after 10 years (Vittadini et al., 2001). Thus, future studies could explore the development of alcohol withdrawal-associated hyperalgesia from transitory to persistent.

Rodent studies show that the stress axes can mediate alcohol withdrawal-induced hyperalgesia (Dina et al., 2006; Dina et al., 2008). Our findings suggest that some of these preclinical findings translate to humans, as epinephrine was elevated in binge drinkers regardless of recent drinking. Therefore, elevated epinephrine in binge drinking may be related to binge drinking-associated with hyperalgesia and explained some of the variance in withdrawal-induced hyperalgesia, albeit only to a small degree (7%). Although we found no further elevation of epinephrine levels with alcohol withdrawal symptoms, others observed elevated epinephrine and norepinephrine levels during alcohol withdrawal (Hawley et al., 1981; Heikkonen et al., 1989; Patkar et al., 2003). Evidence linking HPA axis activation to drinking is mixed. Some observed elevated cortisol levels during withdrawal (Adinoff et al., 1991; Adinoff et al., 2003), whereas others observed blunted cortisol levels in young adult binge drinkers (Orio et al., 2018). We found no group differences in cortisol levels. The inconsistency between ours and other studies is potentially due to differences in the time after the last drinking, the number of years of alcohol use and age of the drinkers. This study defined the window of alcohol withdrawal to include the period up to 48 h after the last drink. Despite withdrawal symptoms, epinephrine and cortisol levels might be recovered in our healthy young adults who engaged in episodic binge drinking. Additionally, the role of stress hormones may be more pronounced in the forced ethanol diet used in rodent studies (Dina et al., 2006, Dina et al., 2008). Indeed, a mouse study showed that after a voluntary ethanol diet, withdrawal-induced hyperalgesia occurred without elevation of corticosterone levels (Smith et al., 2016). However, even in the case of self-administration, blocking the signaling pathway of corticotropin release reduced hyperalgesia in ethanol-dependent rats (Edwards et al., 2012), suggesting cortisol may play a role in later stages of drinking.

Unexpectedly, we did not observe greater negative effect in binge relative to moderate drinkers. Drinkers reported slightly higher depressive symptoms compared to abstainers. Previous findings are mixed, with some finding an association between college binge drinking and depression (Cranford et al., 2009) and others finding a U-shaped pattern, with abstainers and heavy drinkers reporting more depressive symptoms than moderate drinkers (O'Donnell et al., 2006) or no association (Dawson et al., 2005; Geisner et al., 2012). Our null finding in negative effect may be due to our exclusion of individuals with psychiatric diagnoses or treatments. Therefore, binge drinkers in this study may be different from typical college binge drinkers.

Limitations of the current study should be acknowledged. First, we were unable to recruit an equal number of men and women to control for potential sex differences. Therefore, the absence of sex effects in this study may be due to insufficient power. Additionally, participants' self-reported last drinking episode might be inaccurate because it was based on recall. However, the binge drinkers who endorsed drinking within 2 days reported greater acute hangover symptoms at the time of experiment compared to binge drinkers who endorsed no recent drinking and moderate drinkers. Therefore, endorsement of recent drinking was consistent with acute hangover symptoms. Future studies could assess a biomarker (e.g. phosphatidylethanol) to verify self-reported alcohol consumptions (Schröck et al., 2017). More importantly, natural drinking allows to study the effect of 'typical' alcohol withdrawal on pain sensitivity ethically in young adult binge drinkers, and their typical binge drinking was far greater than the minimum binge drinking definition (White et al., 2006). Therefore, our study design has greater external validity. Lastly, this between subject-design was limited in examining the effect of alcohol withdrawal on pain sensitivity because of unknown individual differences in pain sensitivity at baseline.

In summary, this was the first study to demonstrate that alcohol withdrawal-associated hyperalgesia to muscle pressure pain existed in young adult binge drinkers. Additionally, elevated basal concentration of epinephrine was associated with binge drinking. However, cortisol concentration and negative effect were unrelated to either binge drinking or alcohol withdrawal. Additional studies are warranted to disentangle the role and the timeline of stress hormones and negative effect in alcohol withdrawal-induced hyperalgesia.