The Convergent Neuroscience of Affective Pain and Substance Use Disorder

Abstract

Opioids and alcohol are widely used to relieve pain, with their analgesic efficacy stemming from rapid actions on both spinal and supraspinal nociceptive centers. As an extension of these relationships, both substances can be misused in attempts to manage negative affective symptoms stemming from chronic pain. Moreover, excessive use of opioids or alcohol facilitates the development of substance use disorder (SUD) as well as hyperalgesia, or enhanced pain sensitivity. Shared neurobiological mechanisms that promote hyperalgesia development in the context of SUD represent viable candidates for therapeutic intervention, with the ideal strategy capable of reducing both excessive substance use as well as pain symptoms simultaneously. Neurocognitive symptoms associated with SUD, ranging from poor risk management to the affective dimension of pain, are likely mediated by altered activities of key anatomical elements that modulate executive and interoceptive functions, including contributions from key frontocortical regions. To aid future discoveries, novel and translationally valid animal models of chronic pain and SUD remain under intense development and continued refinement. With these tools, future research strategies targeting severe SUD should focus on the common neurobiology between negative reinforcement and affective elements of pain, possibly by reducing excessive stress hormone and neurotransmitter activity within shared circuitry.

Effects of ethanol on mechanical allodynia and dynamic weight bearing in male and female mice with spared nerve injury

“…However, the effectiveness of this strategy is short‐lived as chronic alcohol intake can lead to worsened pain outcomes in the form of alcohol‐induced polyneuropathy and, upon cessation, alcohol‐induced hyperalgesia (Gatch, 2009; Sommer et al, 2018). Thus, alcohol use and chronic pain interact in a positive feedback loop, whereby chronic pain increases excessive alcohol use, which in turn worsens pain outcomes (Cucinello‐Ragland & Edwards, 2021; Ditre et al, 2018; Edwards et al, 2020; Egli et al, 2012; Pahng & Edwards, 2021). However, in clinical populations, it is difficult to assess the directionality of this interaction and dissect the contributing mechanisms, thus necessitating the use of animal models to elucidate directional interactions between the effects of alcohol on pain and vice versa.…”

Transcriptomic signature, bioactivity and safety of a non-hepatoxic analgesic generating AM404 in the mid-brain PAG region

“…Narcotics for pain management is linked to opioid use disorder (OUD) due to its abuse potential 40 . Drug overdose deaths have risen over the past two decades in the U.S. and, in 2021, accounted for 107,000 deaths 41 .…”

Mechanical and Heat Hyperalgesia upon Withdrawal from Chronic Intermittent Ethanol Vapor depends on Sex, Exposure Duration and Blood Alcohol Concentration in Mice

“…Pain is a hallmark symptom in 43–73% of individuals with AUD, and manifests as increased hyperalgesia during alcohol withdrawal due to sensitized central and peripheral mechanisms (Apkarian et al, 2013; Edwards et al, 2020; Maleki et al, 2019; Robins et al, 2019; Zale et al, 2015). Conversely, escalation of alcohol consumption contributes to the development of hyperalgesia and chronic pain (Pahng & Edwards, 2021). Individuals with AUD often drink to relieve or prevent alcohol withdrawal-induced pain (Ditre et al, 2019; Egli et al, 2012; Jakubczyk et al, 2016; Maleki et al, 2019; Witkiewitz et al, 2015).…”