Abnormal pain response in pain-sensitive opiate addicts after prolonged abstinence predicts increased drug craving
Open accessAbstract
Rationale Craving is a primary feature of opiate addiction and is clinically significant because of its potential to trigger opiate use and relapse. Opiate use can also produce abnormal pain perception. We predicted that for opiate addicts (OAs), there may be an association between these two major features of addiction (drug craving and abnormal pain responses).Objectives To examine pain responses in abstinent opiate addicts in comparison with healthy controls using a cold-pressor test (CPT) and investigate the correlations of cue-induced drug craving with pain responses.Material and methods Fifty-four abstinent OAs and 46 healthy subjects participated in the CPT, and the OAs were also exposed to heroin-related cues the day before the pain test. Outcome measures included pain-tolerance time, VAS ratings of pain intensity and distress, and (in the cue-exposure procedure) VAS ratings of heroin craving and anxiety.Results In the CPT, abstinent addicts showed shorter pain-tolerance time (85.1 +/- 14.1 s vs. 133.7 +/- 16.7 s, p < 0.05) and higher ratings of pain distress (61 +/- 3.2 vs. 45.6 +/- 3.2, p < 0.01) compared to healthy controls. When we divided the addicts and controls into pain-sensitive (PS) and pain-tolerant (PT) groups by dichotomizing each group in terms of pain-tolerance time, we again found differences between the two PS groups (37.3 +/- 3.5 s vs. 57.4 +/- 5.1 s, p < 0.01 for pain-tolerance time; 66.7 +/- 3.2 vs. 52.4 +/- 3.3, p < 0.01 for distress ratings). For all participants, pain-tolerance time was negatively correlated with VAS ratings for pain intensity and distress. More importantly, the PS addicts reported greater cue-induced craving than the PT addicts (17.8 +/- 2.2 vs. 4.5 +/- 4.2, p < 0.05). For the addict group as a whole, pain distress (the affective aspect of pain) was positively correlated with intensity of cue-induced craving measured on a different day (r = 0.33, p = 0.01).Conclusions A hyperalgesic state persists for at least 5 months in abstinent OAs and is predictive of cue-induced craving. Longitudinal research is needed to clarify the direction of causation between hyperalgesia and opiate addiction.
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Individuals with a history of opioid addiction show heightened pain perception.
“In humans, heightened pain perception has long been observed in individuals with a history of opioid addiction (Ho and Dole, 1979;Ren et al., 2009).”
From Drug Addiction: Hyperkatifeia/Negative Reinforcement as a Framework for Medications Development (2021) · cites this paper as Ren et al., 2009
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- Authors
- Ren, Z.-Y., Shi, J., Epstein, D. H., Wang, J., & Lu, L.
- Affiliations
- Peking University (CN)
- National Institutes of Health (US)
- Venue
- Psychopharmacology
- Published
- 2009-01-27
- Volume
- 204
- Issue
- 3
- Pages
- 423-429
- ISSN
- 0033-3158 (ISSN-L)
- 1432-2072
- PMC
- PMC3697848
- OpenAlex
- W1991055198
- Cited by
- 101
- References
- 46
- Citations by year
- 2026: 4 · 2025: 4 · 2024: 3 · 2023: 9 · 2022: 7 · 2021: 7 · 2020: 5 · 2019: 9 · 2018: 5 · 2017: 4 · 2016: 7 · 2015: 5 · 2014: 7 · 2013: 8 · 2012: 7
- FWCI
- 5.69
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Psychopharmacology (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health (Z99 DA999999)
- Topics
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Opioid Use Disorder Treatment
- Health Sciences › Medicine › Epidemiology › Substance Abuse Treatment and Outcomes
- Health Sciences › Medicine › Anesthesiology and Pain Medicine › Pain Management and Opioid Use
- Keywords
- opioid use disorder, drug craving, pain sensitivity, pain tolerance, cold pressor test, heroin, cue-induced craving, hyperalgesia, pain-related distress, opioid withdrawal, relapse, pain perception, anxiety, pain intensity
- MeSH terms
- Adult, Anxiety, Cold Temperature, Cues, Exercise Test, Humans, Male, Motivation, Opioid-Related Disorders, Pain, Pain Measurement, Predictive Value of Tests, Recurrence
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