Stress and pain: modality-specific opioid mediation of stress-induced analgesia

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Preclinical research has demonstrated that exposure to acute stress is associated with attenuated pain perception, so called stress-induced analgesia (SIA). Mechanisms of SIA in humans have not been reliably demonstrated. This study examined the role of the endogenous opioid system in the impact of combined interpersonal and mental stressors on evoked pain responses in 84 participants (34 women). Using a within-subject, double-blinded, counterbalanced design, participants were administered either oral placebo or the opioid antagonist naltrexone (50 mg) across two testing sessions. In each session, they experienced two evoked pain stimuli (cold pressor test [CPT], heat pain) after an extended rest period (rest condition) and after exposure to an acute stressor (a combination of public speaking and mental arithmetic challenge; stress condition). Results showed that both stress and opioid blockade produced significant changes in hormonal and cardiovascular measures, consistent with successful induction of acute stress. Stress was associated with attenuated pain perception (SIA) as indicated by significantly increased CPT tolerance. These effects were particularly pronounced in individuals experiencing the stress condition first. More importantly, SIA effects on CPT tolerance were abolished by opioid blockade. There were no significant SIA effects on heat pain responses. This study demonstrates that the endogenous opioid system may mediate effects of acute stress on pain perception, although this effect seems to be qualified by the type of evoked pain stimuli experienced.

Original languageEnglish (US)
Pages (from-to)1397-1407
Number of pages11
JournalJournal of Neural Transmission
Issue number9
StatePublished - Sep 2021

Bibliographical note

Funding Information:
This work was supported by grants R01DA16351 and R01DA027232 (MA), and R01AG048915 and R01DA050334 (SB) from the National Institute of Health, and an AHA-Grant-in-Aid (MA) from the American Heart Association—Minnesota.

Publisher Copyright:
© 2021, The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.


  • Endogenous opioid
  • Naltrexone
  • Opioid blockade
  • Pain
  • Stress
  • Stress-induced analgesia


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