The Convergent Neuroscience of Affective Pain and Substance Use Disorder

Alcohol Res. 2021 Dec 16;41(1):14. doi: 10.35946/arcr.v41.1.14. eCollection 2021.


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.

Keywords: alcohol; cingulate cortex; insula; opioids; pain; reinforcement.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Review

MeSH terms

  • Analgesics, Opioid / therapeutic use
  • Animals
  • Chronic Pain*
  • Hyperalgesia
  • Neurosciences*
  • Substance-Related Disorders* / complications


  • Analgesics, Opioid