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

Cassandra Higgins (Lead / Corresponding author), Blair Smith, Keith Matthews

Research output: Contribution to journalReview article

1 Citation (Scopus)

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 metaanalysis of studies examining evidence for OIH in humans following 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 PICOS framework was used to develop search strategies and findings are reported in accordance the 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. Following 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 NMDA receptor antagonists (primarily evidenced in methadone-maintained populations).

Conclusions: OIH was evident in patients following 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.
Original languageEnglish
Number of pages13
JournalBritish Journal of Anaesthesia
Early online date25 Oct 2018
DOIs
Publication statusE-pub ahead of print - 25 Oct 2018

Fingerprint

Hyperalgesia
Opioid Analgesics
Meta-Analysis
Population
Pain
Pain Threshold
Literature
Methadone
Pain Measurement
N-Methyl-D-Aspartate Receptors
PubMed
Hot Temperature
Databases

Keywords

  • analgesics, opioid
  • hyperalgesia
  • opioid-related disorders
  • pain
  • pain threshold

Cite this

@article{ad318c275e9e4abb9ed9e5d18ff20297,
title = "Evidence of opioid-induced hyperalgesia in clinical populations after chronic opioid exposure: a systematic review and meta-analysis",
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 metaanalysis of studies examining evidence for OIH in humans following 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 PICOS framework was used to develop search strategies and findings are reported in accordance the 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. Following 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 NMDA receptor antagonists (primarily evidenced in methadone-maintained populations). Conclusions: OIH was evident in patients following 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.",
keywords = "analgesics, opioid, hyperalgesia, opioid-related disorders, pain, pain threshold",
author = "Cassandra Higgins and Blair Smith and Keith Matthews",
note = "K.M. has chaired advisory boards for studies of deepbrain stimulation for obsessiveecompulsive disorder spon-sored by Medtronic. He has received educational grants from Cyberonics Inc. and Schering-Plough, and has receivedresearch project funding from Merck Serono, Lundbeck,Reckitt Benckiser, St Jude Medical, and Indivior. He hasreceived travel and accommodation support from Medtronicand St Jude Medical to attend scientific meetings. C.H. was inreceipt of funding from Tenovus Scotland, within the past 36months, for research into the impact of prescribing on opioid-related mortality.",
year = "2018",
month = "10",
day = "25",
doi = "10.1016/j.bja.2018.09.019",
language = "English",
journal = "British Journal of Anaesthesia",
issn = "0007-0912",

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T1 - Evidence of opioid-induced hyperalgesia in clinical populations after chronic opioid exposure

T2 - a systematic review and meta-analysis

AU - Higgins, Cassandra

AU - Smith, Blair

AU - Matthews, Keith

N1 - K.M. has chaired advisory boards for studies of deepbrain stimulation for obsessiveecompulsive disorder spon-sored by Medtronic. He has received educational grants from Cyberonics Inc. and Schering-Plough, and has receivedresearch project funding from Merck Serono, Lundbeck,Reckitt Benckiser, St Jude Medical, and Indivior. He hasreceived travel and accommodation support from Medtronicand St Jude Medical to attend scientific meetings. C.H. was inreceipt of funding from Tenovus Scotland, within the past 36months, for research into the impact of prescribing on opioid-related mortality.

PY - 2018/10/25

Y1 - 2018/10/25

N2 - 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 metaanalysis of studies examining evidence for OIH in humans following 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 PICOS framework was used to develop search strategies and findings are reported in accordance the 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. Following 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 NMDA receptor antagonists (primarily evidenced in methadone-maintained populations). Conclusions: OIH was evident in patients following 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.

AB - 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 metaanalysis of studies examining evidence for OIH in humans following 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 PICOS framework was used to develop search strategies and findings are reported in accordance the 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. Following 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 NMDA receptor antagonists (primarily evidenced in methadone-maintained populations). Conclusions: OIH was evident in patients following 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.

KW - analgesics, opioid

KW - hyperalgesia

KW - opioid-related disorders

KW - pain

KW - pain threshold

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U2 - 10.1016/j.bja.2018.09.019

DO - 10.1016/j.bja.2018.09.019

M3 - Review article

JO - British Journal of Anaesthesia

JF - British Journal of Anaesthesia

SN - 0007-0912

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