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Cited by 131Pain Management and Opioid UseOpioid Use Disorder TreatmentPain Mechanisms and Treatments

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Evidence of opioid-induced hyperalgesia in clinical populations after chronic opioid exposure: a systematic review and meta-analysis

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Higgins, C., Smith, B.H., Matthews, K.·2019·British Journal of Anaesthesia
DOI 10.1016/j.bja.2018.09.019
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Abstract

Background Opioid-induced hyperalgesia (OIH) is well documented in preclinical studies, but findings of clinical studies are less consistent. The objective was to undertake a systematic review and meta-analysis of studies examining evidence for OIH in humans after opioid exposure. Methods Systematic electronic searches utilised six research databases (Embase, Medline, PubMed, CINAHL Plus, Web of Science, and OpenGrey). Manual 'grey' literature searches were also undertaken. The Population, Interventions, Comparators, Outcomes, and Study design (PICOS) framework was used to develop search strategies, and findings are reported in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) Statement. Data synthesis and subgroup analyses were undertaken using a random effects model (DerSimonian-Laird method). Results A total of 6167 articles were identified. After abstract and full-text reviews, 26 articles (involving 2706 participants) were included in the review. There was evidence of OIH, assessed by pain tolerance, in response to noxious thermal (hot and cold) stimuli, but not electrical stimuli. There was no evidence of OIH when assessing pain detection thresholds. OIH was more evident in patients with opioid use disorder than in patients with pain, and in patient groups treated with N-methyl-d-aspartate receptor antagonists (primarily evidenced in methadone-maintained populations). Conclusions OIH was evident in patients after chronic opioid exposure, but findings were dependent upon pain modality and assessment measures. Further studies should consider evaluating both pain threshold and pain tolerance across a range of modalities to ensure assessment validity. Significant subgroup findings suggest that potential confounders of pain judgements, such as illicit substance use, affective characteristics, or coping styles, should be rigorously controlled in future studies.

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  • Medications such as opioids carry increased risks, including adverse side effects, opioid-induced hyperalgesia, abuse, and overdose.

    “Moreover, medications such as opioids carry increased risks, including adverse side effects, opioid-induced hyperalgesia, abuse, and overdose [11–13].”

    From Feasibility and Acceptability of an Abbreviated, Four-Week Mindfulness Program for Chronic Pain Management. (2020) · cites this paper as [13]

    The Conclusions describe debilitating opioid side effects, including the potential for abuse, and identify opioid-induced hyperalgesia as an additional concern. Our copy does not identify overdose as a risk, so it supports only part of the attributed list. (LLM, conf=0.88)

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Metadata

Authors
Higgins, C., Smith, B. H., & Matthews, K.
Affiliations
University of Dundee (GB)
Corresponding author
Higgins, C.
ORCID
Venue
British Journal of Anaesthesia
Publisher
Elsevier BV
Published
2019-06
Volume
122
Issue
6
Pages
e114-e126
ISSN
0007-0912 (ISSN-L)
DOI
10.1016/j.bja.2018.09.019
OpenAlex
W2898102757
Cited by
131
References
5
Citations by year
2026: 10 · 2025: 21 · 2024: 24 · 2023: 24 · 2022: 16 · 2021: 22 · 2020: 11 · 2019: 3
FWCI
2.23
Type
journal article
Language
en
Open access
Licence
Locations
  • British Journal of Anaesthesia (publishedVersion)
  • PubMed (publishedVersion)
  • Discovery Research Portal (University of Dundee) (submittedVersion, cc-by-nc-nd)
Funders
  • St. Jude Medical
  • Schering-Plough
  • Medtronic
  • Tenovus
Topics
  • Health Sciences › Medicine › Anesthesiology and Pain Medicine › Pain Management and Opioid Use
  • Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Opioid Use Disorder Treatment
  • Health Sciences › Medicine › Physiology (medical) › Pain Mechanisms and Treatments
Keywords
opioid-induced hyperalgesia, chronic opioid exposure, opioid use disorder, pain tolerance, pain detection threshold, NMDA receptor antagonists, methadone maintenance treatment, pain assessment validity, opioid analgesia
MeSH terms
Analgesics, Opioid, Drug Administration Schedule, Humans, Hyperalgesia, Pain Measurement, Pain Threshold, Chronic Pain

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