Factors mediating pain-related risk for opioid use disorder

Neuropharmacology. 2021 Mar 15;186:108476. doi: 10.1016/j.neuropharm.2021.108476. Epub 2021 Jan 30.


Pain is a complex experience with far-reaching organismal influences ranging from biological factors to those that are psychological and social. Such influences can serve as pain-related risk factors that represent susceptibilities to opioid use disorder. This review evaluates various pain-related risk factors to form a consensus on those that facilitate opioid abuse. Epidemiological findings represent a high degree of co-occurrence between chronic pain and opioid use disorder that is, in part, driven by an increase in the availability of opioid analgesics and the diversion of their use in a non-medical context. Brain imaging studies in individuals with chronic pain that use/abuse opioids suggest abuse-related mechanisms that are rooted within mesocorticolimbic processing. Preclinical studies suggest that pain states have a limited impact on increasing the rewarding effects of opioids. Indeed, many findings indicate a reduction in the rewarding and reinforcing effects of opioids during pain states. An increase in opioid use may be facilitated by an increase in the availability of opioids and a decrease in access to non-opioid reinforcers that require mobility or social interaction. Moreover, chronic pain and substance abuse conditions are known to impair cognitive function, resulting in deficits in attention and decision making that may promote opioid abuse. A better understanding of pain-related risk factors can improve our knowledge in the development of OUD in persons with pain conditions and can help identify appropriate treatment strategies. This article is part of the special issue on 'Vulnerabilities to Substance Abuse.'.

Keywords: Abuse; Cognition; Opioid; Pain; Reward; Vulnerability.

Publication types

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

MeSH terms

  • Analgesics, Opioid / administration & dosage*
  • Analgesics, Opioid / adverse effects*
  • Animals
  • Chronic Pain / drug therapy*
  • Chronic Pain / metabolism
  • Chronic Pain / psychology*
  • Conditioning, Psychological / drug effects
  • Conditioning, Psychological / physiology
  • Humans
  • Opioid-Related Disorders / metabolism*
  • Opioid-Related Disorders / psychology*
  • Reinforcement, Psychology
  • Risk Factors


  • Analgesics, Opioid