Other studies suggest that people who do not have drinking problems, but have a positive family history of alcoholism (FHP), are more sensitive to painful stimulation than those having no family history of alcoholism (FHN; Stewart et al., 1995). Likewise, people with chronic pain conditions are more likely to have family members with drinking problems (Goldberg et al., 1999; Katon et al., 1985). Another facet of this relationship is revealed in studies showing that people experiencing chronic pain turn to alcohol presumably for relief (e.g., Brennan et al., 2005; Riley and King, 2009). The findings of this study indicated that the incidence of MDE carries a substantial burden in ALC men and women, independently of whether or not they suffer from chronic back/neck pain or frequent/severe headaches. We also found that, although the incidence of PDD was comparable in men and women with ALC, and significantly higher than in CTRL men and women, the incidence of MDE was higher in ALC women independently of the presence or absence of chronic pain. The age of onset of depressive disorders, independently of pain status, was younger for ALC individuals.
Chronic alcohol use itself can produce a characteristic painful neuropathy, while the regular analgesic use of alcohol in the context of nociceptive sensitization and heightened affective pain sensitivity may promote negative reinforcement mechanisms that underlie AUD maintenance and progression. The goal of this review was to provide a broad translational framework that communicates research findings spanning preclinical and clinical studies, including a review of genetic, molecular, behavioral, and social mechanisms that facilitate interactions between persistent pain and alcohol use. We also consider recent evidence that will shape future investigations into novel treatment mechanisms for pain in individuals suffering from AUD. As noted in previous sections, alcohol has been shown to have acute analgesic effects (e.g., Perrino et al., 2008).
Estimates of Co-Occurring Pain and Alcohol Use
Individuals may come to hold beliefs that alcohol will help them manage pain if they have previously perceived a reduction in their pain (or pain-related distress) when drinking. Given evidence that alcohol expectancies may be influenced by socially shared and transmitted beliefs (Donovan, Molina, & Kelly, 2009), it is possible that expectancies for alcohol-induced analgesia may be shaped by social depictions of alcohol as a stress-coping agent. However, we are not aware of any studies that have attempted to assess whether participants held expectancies that drinking may mitigate pain in the context of laboratory pain induction. Future research is needed to identify the levels of alcohol consumption at which the direction of effects changes (e.g., positive to negative).
International Patients
Overall, even though AUDs in themselves do not rank high as a cause of death globally, they are the fourth-most disabling disease category in low- to middle-income countries and the third-most disabling disease category in high-income countries (WHO 2008). Thus, AUDs account for 18.4 million years of life lost to disability (YLDs), or 3.5 percent of all YLDs, in low- and middle-income countries and for 3.9 million YLDs, or 5.7 percent of all YLDs, in high-income countries. However, AUDs do not affect all population subgroups equally; for example, they mainly affect men, globally representing the second-most disabling disease and injury condition for men. In contrast, AUDs are not among the 10 most important causes of disabling disease and injury in women (WHO 2008). We also reviewed evidence that persons seeking treatment for AUD demonstrated hyperalgesia to a pain induction task during the initial stages of alcohol abstinence (Jochum et al., 2010). Although this finding is consistent with evidence of abstinence-induced hyperalgesia derived from animal models, additional research among humans is sorely needed.
Researchers have noted a need for integrated treatments that are informed by knowledge of reciprocal relations between pain and substance use, and initial pilot data suggest that integrated treatments may be beneficial for treating co-occurring pain and substance use disorders (Ilgen et al., 2011). Future work is needed to develop and test integrated interventions for pain and alcohol use across a range of health-care settings. For example, persons with co-occurring pain disorders who engage in treatment for AUD may benefit from taking additional measures to manage their pain during the early stages of alcohol abstinence.
Neural dysregulation, alcohol dependence and chronic pain
Accordingly, we include information pertaining to the strengths and limitations of individual studies as they are discussed within the current review. Finally, we propose future research directions that were directly informed by our assessment of the strengths and limitations of the extant empirical literature. Chronic pain produces multiple electrophysiological and molecular neuroadaptations in the CeA, a number of which are lateralized to the right CeA (e.g., Carrasquillo and Gereau, 2008; Ji and Neugebauer, 2009). The CeA receives functionally distinct inputs from the pontine parabrachial area (PB, nociceptive information) and basolateral amygdala (BLA, sensory-affective information) that are magnified in chronic pain states (Ikeda et al., 2007; Neugebauer et al., 2003). This plasticity is driven in part by an enhancement of glutamatergic systems, most notably activation of group I metabotropic glutamate receptors (mGluR1/mGluR5; Kolber et al., 2010; Li and Neugebauer, 2004; Neugebauer et al., 2003; Ren and Neugebauer, 2010). Neugebauer (2007) speculated that the amygdala facilitates nociceptive signaling in persistent pain states.
When alcohol is administered to rats in a liquid diet for 10 days, analgesic effects peak within 2–4 days and subside with continued administration until pain responses return to baseline levels by day 10 (Gatch, 2009). For example, rats receiving alcohol injections in a distinct environment developed tolerance to alcohol’s analgesic effects regardless of whether they also received tail-flick tests in the same environment (Tiffany et al., 1987). Learning mechanisms do not appear to influence tolerance development when rats receive alcohol in a liquid diet, however, because comparable tolerance effects were observed regardless of whether repeated pain tests were given during alcohol administration (Gatch and Lal, 1999). These studies suggest that conditions for developing tolerance to alcohol analgesia vary, and that experiencing sustained or exaggerated analgesic effects in response to what is amp test alcohol may involve learning mechanisms as observed with tolerance to other actions of alcohol.
- It also predicts that drugs (such as CRF-1 receptor antagonists) acting upon the shared neurocircuits would likely be effective for treating alcohol dependence and pain disorders whereas other pharmacotherapies targeting disorder-specific mechanisms would be effective for one disorder, but not the others.
- Finally, studies that have examined pain-inhibitory effects of oral alcohol administration typically utilized beverages containing sugar to conceal alcohol dosage (e.g., Brown & Cutter, 1977).
- Our review of the literature identified a range of biopsychosocial factors and health-related behaviors (e.g., tobacco use, illicit drug use) that may covary with both alcohol use and pain.
- The onset of chronic pain may precede memory problems, and chronic pain has been shown to increase the risk of dementia in older adults (Whitlock et al., 2017).
- Studies in rodents selectively bred for differences in alcohol preference also provide partial evidence alcohol preference and pain response covary (Chester et al., 2002; Kampov-Polevoy et al., 1996; but see Kimpel et al., 2003).
There is substantial evidence that alcohol consumption can cause unprovoked seizures, and researchers have identified plausible biological pathways that may underlie this relationship (Samokhvalov et al. 2010a). Most of the relevant studies found that a high percentage of heavy alcohol users with epilepsy meet the criteria of alcohol dependence. We also explored the breakdown of incidence by sex, and the results are presented in Figure 3. Overall, we found that the incidence of depressive disorders was the highest among ALC women and the lowest among CTRL men. However, PDD was higher in ALC women than in ALC men, in both groups with no history of chronic pain. The incidence of PDD was comparable in ALC men and ALC women with a history of back/neck pain or severe headaches.
Regarding the age of onset of the various conditions, we found that the onset of MDE in the ALC group was younger than in the CTRL group, whether or not either group experienced pain. We looked at the temporal relations between the ages of onset of each of the depressive disorders to determine if onset of ALC, preceded onset of MDE, MDD, or PDD. We found that there were no significantly different temporal patterns in onset of any of the depressive disorders relative to ALC onset. The comparability between ages of onset of alcohol abuse and depressive disorders may be suggestive of overlapping genetic predispositions for these disorders 34. Pain sensitivity and alcohol analgesia are enhanced in alcohol dependent patients and FHP individuals and may also be altered in animal models of genetic vulnerability for alcohol dependence.
It is influenced by a host of familial, biological, environmental, and socioeconomic mediators that affect drinking behavior and susceptibility to pain disorders. To our knowledge, all of the studies that examined prospective relations between pain and subsequent alcohol consumption were limited to samples consisting of older adults who reported low levels of baseline drinking and did not necessarily have chronic pain (Bobo et al., 2012; Brennan et al., 2011; Brennan & Soohoo, 2013). Future work in this area should test relations between pain and subsequent patterns of alcohol consumption using representative samples drawn from the general population, treatment-seeking chronic pain patients, and persons seeking treatment for AUD. For example, longitudinal studies may test whether persons with chronic pain are at greater risk for the development or persistence of AUD. Given evidence that pain may motivate alcohol consumption, researchers have hypothesized that recurring pain may increase alcohol consumption over time (Egli et al., 2012), and further research is needed to identify pain-related factors that may contribute to this transition (e.g., pain frequency, pain duration, affective disturbance). Additionally, researchers have suggested that persons who utilize effective pain coping strategies may experience reduced pain and pain-related distress, which, in turn, could result in decreased motivation to use substances (Ditre, Heckman, Butts, & Brandon, 2010).
In the following section, we briefly examine a selection of biopsychosocial factors that are relevant to both pain and alcohol use. The link between alcohol and almost all kinds of unintentional injuries has long been established. 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). We also compared ALC and CTRL cohorts on age of onset of depressive disorders for each pain condition.
