The role of stress pathways in regulating central and peripheral mechanisms of chronic pain and alcohol dependence is also discussed. Further studies are necessary to understand how these neural circuits are regulated in comorbid conditions of alcoholism and chronic pain. An association between chronic pain conditions and alcohol dependence has been revealed in numerous studies with episodes of alcohol abuse antedating chronic pain in some people and alcohol dependence emerging after the onset of chronic pain in others. An improved understanding of the effects of alcohol on pain, the role of pain in alcohol misuse, and potential interactions between alcohol and opioids during pain treatment hopefully will improve treatment outcomes for patients in pain. Recent studies suggest that around 1 in 4 adults in chronic pain reports self-medicating with alcohol, and 43–73 percent of people with alcohol use disorder (AUD) report experiencing chronic pain. A comprehensive approach to the treatment ofalcohol addiction, which considers chronic conditions like chronic pain, is necessary for effective treatment of both.
Comorbidity of Problematic Alcohol Use and Pain
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 . Early theories explaining pain in terms of direct dedicated pathways for nociception began to be questioned by paradoxical observations such as the observation of less than severe pain or no pain in soldiers with extensive wounds . For example, sucrose-fading procedure exposed rats to mixtures of ethanol and sucrose to drive high levels of consumption followed by the gradual reduction of sucrose to zero 148, 149. The possible involvement of alcohol’s effect on inflammation and inflammatory cytokines acting on µ-opioid receptor regulation also needs further investigation . For example, rats show a greater consumption of alcohol over water immediately after an expected highly preferred reward is omitted or reduced to a less preferred value 136–138.
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 . 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) . The PB is one critical structure receiving nociceptive input that appears to diverge into at least two distinct pathways. The neurotransmitters involved in excitatory interactions include glutamate and substance P, while inhibitory neurotransmitters include GABA. Representative components of the pain system identified in the narrative review and the 3 dimensions of physical and psychological pain .
These findings provide evidence of the participation of DORs (and α2-adrenergic receptors in the spinal cord) in mediating alcohol withdrawal-induced allodynia. The pharmacological blockade of DORs with naltrindole in alcohol-naïve mice produced an allodynic effect, and a low dose of naltrindole that did not produce allodynia per se prolonged the duration of alcohol withdrawal-induced allodynia. The intrathecal administration of clonidine, an α2-adrenergic receptor agonist that is used to treat alcohol withdrawal in humans, reversed alcohol withdrawal-induced allodynia. These findings suggest that alcohol withdrawal-induced allodynia depends on the amount of alcohol exposure. Mechanical hypersensitivity in alcohol-exposed rats increased at 5 weeks after the cessation of alcohol, indicating the long-lasting allodynic effects of alcohol withdrawal. Equally effective in producing alcohol dependence is the chronic, intermittent alcohol vapor exposure model, where animals are typically exposed to alcohol vapor for 14 hours/day (intoxication), followed by 10 hour with vapor off (withdrawal).
Evidence indicating a complex association between alcohol use and health includes several decades of evidence for the protective benefits of moderate alcohol use on cardiometabolic health, for example, 122, 123. Notwithstanding our current knowledge of alcohol misuse as a leading risk factor for disease burden, since antiquity there has been an enduring belief in the medicinal power of alcohol. Acute but excessive amounts of alcohol may also interfere with the innate immune system defense against bacterial infection by injuring hematopoietic tissue and impairing bone marrow production of granylocytes (including neutrophils, eosinophils, and basophils) increasing vulnerably to bacterial infection and sepsis . Chronic alcohol consumption often leads to reduced intake of dietary thiamine (Vitamin B1) which is further exacerbated by alcohol-induced malabsorption of this essential vitamin.
Nociception and nociceptive-pain
The goal of this critical review is to extend recent reviews on the topic of alcohol and pain (Egli et al., 2012, Zale et al., 2015). Riley III, J.L., and King, C. Self-report of alcohol use for pain in a multi-ethnic community sample. If you’re taking medications to manage your pain, talk to your doctor or pharmacist about any reactions that may result from mixing them with alcohol.
Association between alcohol consumption and chronic pain: a systematic review and meta-analysis
As such, NHANES is particularly well-suited for examining the intersection of these two important public health issues in a comprehensive and population-level manner. This aligns with previous research which suggests ketamine withdrawal ketamine detox that marital status may influence substance use behaviors due to differences in social support systems33. Substance use can alter the brain’s reward system, increasing pain sensitivity and amplifying discomfort32.
Benfotiamine for the treatment of alcohol related peripheral neuropathy
Preclinical (for reviews see Neugebauer et al., 2004, 2009) and clinical (reviewed in Simons et al., 2012) studies established a close correlation between amygdala activity and pain. Projection neurons in the lateral regions of the CeA, including CeLC neurons interconnected with the substantia innominata, form connections with the brainstem and forebrain areas involved in the expression of aversive behaviors and pain modulation such as the periaqueductal gray (Bourgeais et al., 2001; Neugebauer et al., 2004). Importantly, this strength remained invariant over the longitudinal study period (over 4 measurements in about 12 weeks, 3, 6, and 12 months from onset of acute/sub-acute back pain). This notion was confirmed by showing that, during the thermal stimulus, back pain patients experienced a simultaneous decrease of their own ongoing back pain, and thus these patients actually enjoyed the thermal pain only if their attention was directed to their own pain. The latter observations led to the use of the new technology, which was just becoming available, of quantifying brain gray matter density and comparing it between patients and healthy subjects. The National Institute of Alcohol Abuse and Alcoholism organized a satellite symposium that highlighted central and peripheral mechanisms involved in pain transmission and in the development of alcohol and drug dependence.
The serotonin/norepinephrine re-uptake inhibitors (SNRIs), duloxetine and venlafaxine, have a well-documented efficacy in painful polyneuropathy 117, 118. They have central effects on pain transmission and block the active re-uptake of norepinephrine and serotonin. Tricyclic antidepressants (TCAs) are often the first line drugs to alleviate neuropathic pain symptoms. A mechanism of cisplatin chemotherapy-induced peripheral neuropathy was elucidated in an in vitro mouse model. Clinical trials of methylcobalamin alone or vitamin B12 combined with other B vitamins found overall symptomatic relief of neuropathy symptoms was more pronounced than electrophysiological findings .
- The study, therefore, demonstrates that, for chronic pain patients, the value of acute painful stimuli is determined in relation to their chronic pain.
- Over 88,000 people die each year in the U.S. due to alcohol-related causes, making alcohol the fourth leading cause of preventable death in the U.S. (Stahre et al., 2014).
- 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.
- The link between alcohol consumption and chronic pain is complex.
- In this installment, Jonathan Stoever, MD, a pulmonologist with Confluence Health in Wenatchee, Washington, discusses bronchitis and what patients should know.
- They also help patients to engage with their own reasons or needs, which make attempting change worthwhile, and to aid in the formulation of realistic, achievable plans for change that inspire confidence and hope.
Yet, there is also evidence that men with chronic pain may be more at risk of AUD and depression, as well as report a stronger association between pain, depression, and alcohol use, as compared to women (Barry et al., 2013, Brown, 2015, Manubay et al., 2015). Women are more likely to develop chronic pain, are more sensitive to pain in controlled laboratory studies, and may be at higher risk of developing persistent pain after injury (Linnstaedt et al., 2015, Rosen et al., 2017, Sorge and Totsch, 2017). Individuals with chronic pain tend to report higher levels of alcohol use and AUD than the general population (Hoffmann et al., 1995, Vowles et al., 2018) and also report using alcohol to medicate acute pain symptoms (Alford et al., 2016, Brennan et al., 2011, Riley and King, 2009). Alcohol is a popular choice for those who turn to substances to mitigate their pain; however, its effects on the body can be especially destructive for those with chronic pain. However, while the prevalence of specific substances or treatment approaches may have evolved, the underlying association between chronic pain and substance use is likely to remain relevant and be the same.
- He wants them to instead focus on their health span.
- Once Ms B recovered and was medically stable, she was started on oral buprenorphine for pain control.
- An improved understanding of the effects of alcohol on pain, the role of pain in alcohol misuse, and potential interactions between alcohol and opioids during pain treatment hopefully will improve treatment outcomes for patients in pain.
- This has been attributed to neuroadaptive changes in the extended amygdala resulting from chronic alcohol intoxication and withdrawal.
- These resources provide a comprehensive approach to addressing the physical, psychological, and social aspects of addiction, helping individuals build a strong foundation for long-term sobriety.
- This suggests that these pathways are potential targets for novel pharmacological agents for the treatment of inflammatory as well as neuropathic pain .
- Furthermore, chronic mifepristone treatment decreased alcohol drinking in humans with alcohol use disorder (Vendruscolo et al., 2015).
As yet there is no effective therapeutic intervention available for relieving the neuropathic pain due to chronic alcohol consumption. Thus there is a need to investigate all the above mentioned agents in animal models of alcoholic neuropathy as well clinically in patients suffering from this disorder. Valproate demonstrated varying effects in different studies of neuropathic pain, with three studies from one group reporting high efficacy 125–127 and others failing to find an effect 128, 129. Lamotrigine was effective in relieving central post stroke pain and painful diabetic polyneuropathy , but recent larger studies have failed to show a pain relieving effect in mixed neuropathic pain and painful polyneuropathy . Thus, further preclinical and clinical studies are required to assess of this molecule in alcoholic neuropathy.
It remains to be determined whether CRFR1 effects in CeA on hyperalgesia can be attributed to their expression on specific subsets of CeA projection cells. The corticotropin-releasing factor type-1 receptor (CRFR1) may be similarly leveraged to modulate specific circuits for reducing pain in individuals with AUD. If specific receptor subtypes are preferentially enriched on specific sets of projection neurons, then pharmacological modulation of those receptors may present a unique opportunity to modulate that circuit for reducing pain-like outcomes with minimal off-target effects. Recent work from our group showed that alcohol dependent rats exhibit weaker connectivity between the central amygdala (CeA) and ventrolateral periaqueductal gray during withdrawal.
However, future studies are necessary to understand how these neural circuits are regulated in comorbid conditions of alcoholism and chronic pain. The reward and emotional pathways mediate chronic pain and drug addiction and the interaction between stress hormones and alcohol use influence neuropathic pain. Thus, targeting dysregulated brain stress signaling, with a focus on CRF systems (Logrip et al., 2011) may represent a valuable therapeutic avenue for severing the destructive intersection of chronic pain, affective disorders, and alcoholism. maverick sober living And, while, the combined local administration of alcohol to the peripheral nervous system, with and without stress axis hormones, may provide a model system to study the independent effects of stress and alcohol, a considerable number of parametric studies will be required to establish an in vitro model of the combined effects of alcohol, catecholamines and glucocorticoids on nociceptor function. Given the recent development of a model in which alcohol is applied to the peripheral nervous system in such a way as to exclude actions in the central nervous system, it should be possible to determine if PKCε mediates the alcohol and/or stress hormone contribution to alcohol-induced painful peripheral neuropathy.
It also has potential to decrease cravings for alcohol, which is in line with the patient’s goals. Pregabalin was selected as a preferred therapeutic alternative for the management of the patient’s primarily neuropathic pain. Because of the patient’s reported ongoing use of alcohol, acetaminophen and NSAIDs are not considered safe alternatives. Opioids are not a preferred alternative because of the patient’s high risk profile for misuse. Use of cannabinoids (eg, nabilone, dronabinol, nabiximols) may affect alcohol-related dopamine release, influencing alcohol consumption.44–46 This may worsen alcohol dependence in the context of concurrent cannabinoid use. In the active comparison study, pregabalin was not different characteristics of an enabler from lorazepam but better than tiapride from survival function of time to dropout.
It’s also important to note that the data were collected over a decade ago, and patterns of both chronic pain and substance use may have changed since. The cross-sectional nature of the NHANES data limits the ability to determine temporal and causal relationships between chronic pain and substance use. This gender disparity may reflect various biological, psychological, and socio-cultural factors, including greater social acceptance of substance use among men, increased opportunities for exposure, differences in stress-coping strategies, and higher risk-taking behaviors35. Finally, like several previous studies our study revealed that men were at a higher risk of engaging in polysubstance use compared to women.
In fact, alcohol can interact badly with a number of medications. Many over-the-counter and prescription medications carry warnings not to take drugs with alcohol. This can change the quality of our experience in ways that change the subjective experience of pain as well as the suffering precipitated by it. ACT emphasizes building psychological flexibility and emphasizes values-congruent practices, while DBT emphasizes the development of emotional regulation and distress tolerance skills. This suggests that different molecular mechanisms may drive the two types of pain. While conventional medicine can offer some relief, the potential side effects or addictive nature of many of the medications render long term use undesirable.
