For humans, the nociceptive flexion reflex (NFR) is a popular objective neurophysiological tool for the assessment of nociception and nociceptive-pain. This polysynaptic reflex is activated involuntarily by noxious stimuli applied to a limb causing a protective withdrawal response. Because the NFR is moderately positively correlated with verbal reports of pain this measure is also used as an indicator of nociceptive-pain 14. However, there are reports of the dissociation between the NFR and nociceptive-pain under clinically relevant (e.g., chronic pain syndromes) and normal situations 15–17. It has also been shown under experimental contexts that stimulus-dependent withdrawal reflexes are influenced by cognitive and emotional factors modulating descending control of spinal circuits 18.

While based on these studies, it seems reasonable to conclude that chronic pain causes memory problems, it is also likely that chronic pain and memory problems may occur in parallel due to damage in brain structures (such as hippocampus) shared between the two, and caused by something else, without either necessarily causing the other. The prefrontal cortex, amygdala, and nucleus accumbens are all essential components of the alcoholism/addiction circuitry (Volkow & McLellan, 2016). Recurrent pain is highly prevalent among treatment seeking problem drinkers (Boissoneault, Lewis, & Nixon, 2018; Sheu et al., 2008), and alcoholism is considered a risk factor, both for the development of chronic pain in patients who suffer from AUD, and for relapse in those attempting to remain abstinent. But despite numerous reports on the associations between chronic pain and AUD, the underlying mechanisms involved in linking them remain elusive. AUD may share common neural pathways with chronic pain, which may facilitate pain affecting alcohol use patterns, or facilitate modulatory effects of alcohol on pain processing, thereby precipitating the risk of chronic pain development. It is influenced by a host of familial, biological, environmental, and socioeconomic mediators that affect drinking behavior and susceptibility to pain disorders.

Influences of Alcohol on Processes Involved in Pain Perception

• The prefrontal cortex, amygdala, and nucleus accumbens are all essential components of the alcoholism/addiction circuitry (Volkow & McLellan, 2016).
• The possible involvement of alcohol’s effect on inflammation and inflammatory cytokines acting on µ-opioid receptor regulation also needs further investigation 141.
• It not only affects pain directly but can also interact with pain medications, impact sleep, increase stress, and reduce our quality of life.
• This sensitization of nociceptors results in increased sensitivity at the site of exposure to the noxious stimulus (primary hyperalgesia) and to the surrounding area (secondary hyperalgesia) and can also induce the sensation of pain from thermal or mechanical stimuli that are normally innocuous (i.e., allodynia) 3, 4.

That’s because alcohol can interact negatively with a number of medications, including acetaminophen (Tylenol), aspirin and opioids. Mixing opioids and alcohol can be particularly dangerous since both substances suppress respiration and can cause a person to stop breathing. It’s been estimated that alcohol–medication interactions may be a factor in at least 25 percent of emergency room visits. In the meantime, while chronic pain should always be evaluated by a medical professional, there are many options for medication/opioid-based treatment, drawing on complementary and alternative approaches. Alcohol Use Disorder and pain are complex conditions having multiple additional etiological impacts reviewed elsewhere (Oscar-Berman et al., 2014; Zale et al., 2015).

The terms analgesia and antinociception are often used synonymously with hypoalgesia, however the former is more appropriately defined as the absence of pain in response to a stimulus that would otherwise be subjectively experienced as painful whereas hypoalgesia and antinociception refer to diminished pain. Some ways we can relieve chronic pain include medications, alternative medicine practices, and physical therapy. So, it’s not that we’re any less hurt or that alcohol makes the pain go away, it’s that the messaging within our brain and body get disrupted, and we don’t register the signal of pain as well. Even some of the non-dependent mice — 40% of non-dependent male mice and 50% of non-dependent female mice — showed allodynia compared to the alcohol-naïve control group.

Molecular aspects of nociception

Placebo reduction of nociceptive processing at the level of the spinal cord shows the role of cognition in modulating nociceptive-pain at the level of sensory-discrimination dimension 153. As seen in other sensory modalities, top-down processing is fundamental to the construction of percepts resulting in individual differences in why alcohol worsens chronic pain perceptions of the external world as revealed by ambiguous stimuli. As an example, consider the image of “the dress” that took the internet by storm in 2015 generating substantial interest among the public and the vision science community.

Another family history study on prepubertal children suggested that the risk of prepubertal onset of major depressive disorder in families with a high aggregation of affective disorders is higher when there also is a high prevalence of AUD in the families (Puig-Antich et al., 1989). Alcohol Use Disorder (AUD) and chronic pain are widespread conditions with extensive public health burden. This review seeks to describe neuroanatomical links and major mediating influences between AUD and chronic pain, in the service of identifying factors that predict the risk of chronic pain in precipitating or facilitating AUD. To date, the lack of preclinical, or animal, models of alcoholic neuropathic pain limited the investigation of pathological mechanisms underlying the onset of neuropathic pain in people with alcohol use disorder. Recent scientific, political, and legal developments are rapidly shifting how health professionals recommend and prescribe analgesic medications and other interventions to combat what will be a continuing (if not growing) global epidemic of chronic pain (Global Burden of Diseases and Injuries Collaborators, 2020).

The phenomena of phantom limb (persistent sensations in a missing or amputated limb) and placebo hypoalgesia (pain relief from the expectation of a beneficial or therapeutic outcome) inspired Melzack to include the evaluative-cognitive dimension in the neuromatrix theory of pain perception 66. Brain structures implicated in the cognitive modulation of pain include the anterior insular cortex (IC) and anterior cingulate cortex (ACC), structures shared with circuitry implicated in emotion, reward, and drug and alcohol addiction 73, 152. The PAG along the caudal rostral axis of the midbrain is the most well-characterized pathway involved in descending pain modulation through its connection with the dorsolateral PFC, rostral ACC, hypothalamus, and ventromedial medulla, and spinal cord 71, 153. Experimental human studies on placebo hypoalgesia and expectation effects show that the descending modulation of pain pathways are mediated primarily through endogenous opioids and dopaminergic signaling mediating negatively reinforcing pain relief or expectations of pain persistence, for example 154–156. In this narrative review, we aimed to present an overview of the current understanding of the mechanisms of nociception, the sensation of nociceptive-pain, and pain perception to inform and guide research on the contribution of the pain system in alcohol use, misuse, and dependence. Conventional wisdom influenced by the centuries-old Cartesian model of pain views physical hurt as a nociceptive experience that is directly translated into the sensation and perception of pain.

Dysregulation of the Mesocorticolimbic Reward Network.

These findings indicate that the PB is involved in the aversive and rewarding properties of alcohol. Although alcohol exposure (by experimental treatment or self-administration procedures) is initially aversive, the aversive properties decline with repeated exposure to ethanol and the rewarding properties increase. Indeed, c-FOS activation following acute ethanol administration causes c-FOS activation to decline (desensitize) in the PB and other alcohol-sensitive brain structures at different rates with the EW showing more sustained sensitivity than the other nuclei 91. When we add pain relief to that, our desire to drink can increase, heightening our risk of dependence. In this way, the consequences of drinking with chronic pain become greater, and our goal — relieving our pain — becomes all the more remote. It’s not unusual for people with chronic pain to consume alcohol to self-medicate—to drink to help sand down the sharp edges of their pain and turn down the volume of their discomfort.

General Health

• Paradoxically, while acute alcohol drinking reduces sensitivity to pain repeated administration of alcohol, like opioids and other analgesic drugs, results in greater sensitivity to physical nociceptive-pain-inducing stimuli (hyperalgesia).
• Because pain has a negative impact on alcohol overconsumption among individuals in treatment for AUD, researchers have investigated whether addressing pain within the context of treatment for alcohol or substance use disorders may be beneficial for drinking outcomes.
• Or it may be negative reinforcement as a result of the temporary reduction of an unpleasant experience such as transient relief of physical or psychological pain.
• ACT emphasizes building psychological flexibility and emphasizes values-congruent practices, while DBT emphasizes the development of emotional regulation and distress tolerance skills.
• Figure 1 shows several of the components of the pain system identified in this review as it relates to Melzack’s conceptualization of the “neuromatrix”.

Many other inflammatory signals also impact on nociceptors as downstream targets by inducing upregulation of ion channels including histamine, bradykinins, prostaglandin E2, nerve growth factor (NGF), and protons H+. Hypersensitivity of neural circuitry also occurs in the spinal and supraspinal circuits of the central nervous system (CNS) and by consensus is conceptualized as central sensitization 2, 5. The neurotransmitters involved in excitatory interactions include glutamate and substance P, while inhibitory neurotransmitters include GABA. The secondary neurons cross the midline and project to supraspinal structures via two primary paths through the thalamus as part of the anterolateral system (except for nociceptors of the face which follows a separate route to the thalamus via the trigeminal nerve). A separate medial route carries information to the periaqueductal gray (PAG) and the parabrachial nucleus (PB) at the junction of the pons and midbrain in route to the amygdala and other forebrain structures attributed to the affective-motivational and evaluative-cognitive dimensions of the neuromatrix 67, 68. Interestingly, experiments with decerebrate animals which remove the integration of forebrain structures with the hindbrain by surgical separation of the connection with the brainstem and spinal cord have demonstrated intact escape-like behaviors (i.e., nocifensive behaviors) to specific noxious stimuli 69.

Alcohol interacts with various neurotransmitters such as gamma-aminobutyric acid (GABA), glutamate, dopamine, acetylcholine, and serotonin, or their receptors in the central nervous system, particularly within the descending pain modulatory system interfering with the balance between excitatory and inhibitory neurotransmitters (Valenzuela, 1997). For instance, while alcohol consumption initially potentiates GABA, a major inhibitory neurotransmitter, the number of GABA receptors declines with excessive drinking over a long period of time (Davies, 2003; Oscar-Berman & Marinkovic, 2003; Valenzuela, 1997). This also may interfere with efficiency in descending pain inhibition at the midbrain level and precipitate development of chronic pain conditions in which deficiency in descending pain modulatory system is thought to be a central cause (Ossipov et al., 2014). Occasional acute physical disturbances or infrequent experiences that may be a potential threat (stressor) result in an adaptive protective response followed by the return to a static but “normal” homeostatic function. Homeostasis makes sense within a physical system that maintains stable features to match an environment that is unchanging notwithstanding irregular and temporary perturbations. However, with the emergence of a chronic environmental stressor or persistent repeated exposures to physical insults the maintenance of a “normal” homeostatic baseline no longer makes sense.

Affective-emotional brain structures and alcohol

When levels of inflammatory proteins were measured, the researchers discovered that while inflammation pathways were elevated in both dependent and non-dependent mice, specific molecules were only increased in dependent mice. It also indicates which inflammatory proteins may be useful as potential targets for intervention to combat alcohol-related pain. Follow-up studies are focused on how these molecules might be used to diagnose and more effectively treat alcohol-related chronic pain conditions.

Chronic alcohol drinking makes pain worse

Alcohol can temporarily reduce our perception of pain by slowing down messaging in our brain, but it doesn’t actually make the pain go away. Let’s say we’re sick and tired of the constant pain, and we decide to have a drink to take the edge off. When we drink, our brain releases serotonin and dopamine (our brain’s “feel good” hormones), which help us relax in the moment and feel a sense of pleasure. Alcohol can also help us relax physiologically by slowing down our heartbeat and releasing tension in our muscles (again, temporarily).

The PB is one critical structure receiving nociceptive input that appears to diverge into at least two distinct pathways. One neural pathway for the direct activation of nocifensive behavior (via the ventromedial hypothalamus or lateral PAG) and another pathway for the experience of pain and learning involving the forebrain structures, bed nucleus of the stria terminalis (BNST) or central nucleus of the amygdala (CeA) 70. Thus, ascending nociceptive information (along with descending modulating influences) is integrated at many levels of the neuroaxis resulting in neural pathways that mediate many nociception-related functions – from the activation of nocifensive behaviors to the integration of nociceptive information with affect, emotion, cognition and learning 71.