Alcohol and Pain: A Translational Review of Preclinical and Clinical Findings to Inform Future Treatment Strategies

The researchers found increased levels of IBA-1 and CSF-1 in the spinal cord tissue of mice with alcohol withdrawal-related allodynia and mice with alcohol-induced neuropathic pain. This phenomenon is more common in women, affecting around 60% of cases, than in men, in whom it affects around 50% of cases. Moreover, recent research suggests that as many as 28 percent of people experiencing chronic pain turn to alcohol to alleviate their suffering. Despite this, using alcohol to alleviate pain places people at risk for a number of harmful health consequences. Roberto’s group is continuing studies on how these molecules might be used to diagnose or treat alcohol-related chronic pain conditions. In dependent mice, allodynia developed during alcohol withdrawal, and subsequent alcohol access significantly decreased pain sensitivity.

Allostatic-like dysregulation of shared neurocircuitries and maverick house rehab neurochemicals has been invoked to explain vulnerability to alcohol addiction resulting from chronic alcohol and stress (Breese et al., 2011; Uhart and Wand, 2009), as well as comorbidity between depression and pain disorders (Robinson et al., 2009). We propose a model (Fig. 3) where alcohol, stressors and injury are similarly capable of dysregulating a common set of neural substrates (including the CeA, NAc, ACC, and insula; symbolized by the outer oval in Fig. 3) to engender a heightened state of sensitivity to emotional and sensory pain. Under normal, homeostatic conditions (symbolized by the upper inner oval), alcohol intoxication produces emotional and sensory pain though a compensatory opponent response (i.e., withdrawal) to an initial rewarding and analgesic action whereas emotional and sensory pain comprise the initial response to trauma and injury.

In cases where pain among AUD individuals results from a comorbid condition (e.g., cancer, neuralgia, fibromyalgia), abstinence of any duration can reveal the presence and intensity of pain that was previously being masked by the analgesic effects of alcohol. This dynamic can present unique challenges for recovering individuals suffering from acute and/or chronic pain, as well as for the physicians responsible for treating both conditions. It depends on the blood alcohol concentration (BAC) and shows an exponential dose-response relationship (Taylor et al. 2010). However, the epidemiological literature shows that even at lower BACs, injury risk is increased compared with no alcohol consumption (Taylor et al. 2010). A recent review on the topic of alcohol withdrawal and hyperalgesia in animal models identified down-regulation of adenosine receptors, and up-regulation of L-type calcium channels, as likely mediators of alcohol withdrawal-induced hyperalgesia (Gatch, 2009).

How does alcohol make chronic pain worse?

Indeed, a recent consensus meeting determined that there is not yet sufficient evidence to conclude that alcohol has a causal impact on HIV infection (Parry et al. 2009). However, it can be argued that experimental studies in which alcohol consumption led to a greater inclination to engage in unsafe sex indicate that some causal relationship between alcohol and HIV infection exists (e.g., George et al. 2009; Norris et al. 2009). Understanding the similarities and differences between the ALC and CTRL cohorts in depressive disorders is particularly intriguing because alcohol abuse is more prevalent in men than in women 31, while chronic pain disorders and depressive disorders tend to have a higher prevalence in women 32. Moreover, in a longitudinal study, Boissoneault and colleagues 33, found that depression was predictive of alcohol problems only in women but not in men. Potential mechanisms of the acute pain inhibitory effects of alcohol include activation of the endogenous opioid system and response expectancies.

Health Topics: Pain and Alcohol

Among the problem drinkers who experienced moderate to severe pain, almost 57% of men and 59% of women reported using alcohol for pain management, compared to 21% of nonproblem-drinking men and women with the same level of pain. Research designs that allow for naturalistic assessment of covariation between pain and alcohol consumption would yield important information regarding event-level temporal associations. For example, ecological momentary assessment (EMA) may provide an optimal method for assessing such covariation in near-real-time.

Dysfunction in descending pain modulatory circuits is thought to play an important role in the chronification of pain (Ossipov et al., 2014). This circuit, which controls top-down modulation of pain, receives inputs arising from multiple regions in the brain, including the hypothalamus, amygdala, and the rostral anterior cingulate cortex (Figure 2). These regions feed into the rostral ventromedial medulla, which includes the midline nucleus raphe and periaqueductal gray matter that have neural pathways to the spinal dorsal horn. Together, they form the descending pain modulatory system from the brain to the spinal cord and can modulate nociceptive processing by providing a substrate for cortical and subcortical structures to exert their influence.

1. Nevertheless, laboratory studies suggest that the presence of hyperkatifeia and enhanced responsiveness to painful stimulation may not always be sufficient to increase alcohol drinking.
2. These individuals would be in a situation that is analogous to what has been described for opioid analgesic misuse risk in chronic, low-back pain patients who had been prescribed opioid analgesics (Marino et al., 2013).
3. While not a prominent trait in chronic pain patients, impulsivity may be especially relevant to individuals with AUD who suffer from chronic pain.
4. We then review studies examining both the effects of alcohol on pain and the effects of pain on alcohol use, and integrate these findings to conceptualize a series of reciprocal interrelations between pain and alcohol.

Evidence of Curvilinear Associations between Alcohol Consumption and Pain Conditions

In this review, we highlight common neural and psychosocial mechanisms underlying pain and alcohol use and identify current gaps in the literature regarding alcohol/pain interactions. The prevalence of chronic excessive alcohol use is relatively high among adult patients with CP conditions, and the prevalence of CP is increased in patients with AUD. Much evidence suggests that the mechanisms underlying AUD and the processes involved in the dysregulation of pain signaling potentially intersect. There is overlap in some nonpharmacological treatments that are used for treating both AUD and CP, specifically those that involve cognitive and behavioral interventions. Several classes of prescribed pain medications can interact with alcohol, including anti-inflammatory agents, muscle relaxants, and opioid analgesics; these therapies can be harmful to patients with AUD.

Studies utilizing representative population-based and clinical samples are needed to generate prevalence estimates that account for varying definitions of pain (e.g., chronic pain duration, type of pain condition) and alcohol use (e.g., amount consumed, AUD). Future research would benefit from a more detailed and consistent approach to the quantification and operationalization of self-reported alcohol consumption. Future research should also attempt to differentiate between lifetime abstainers and those who abstain later in life (e.g., due to illness that prohibits alcohol use or recovery from AUD), as pain-related outcomes may vary as a function of alcohol exposure. The current review also identified numerous sociodemographic, psychiatric, and environmental factors common to both pain and alcohol use (e.g., socioeconomic status, anxiety and depressive disorders, tobacco smoking). As these factors may confound the study of relations between pain and alcohol, future research would benefit from accounting for these relevant third variables. Future research may also examine other relevant third variables (e.g., comorbid medical conditions, emotional distress) that could further inform our evolving conceptualization of reciprocal relations between pain and alcohol use.