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

Cassandra Higgins; Blair Smith; Keith Matthews

doi:10.1016/j.bja.2018.09.019

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

Population Health and Genomics

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88 Citations (Scopus)

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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.

Original language	English
Pages (from-to)	e114-e126
Number of pages	13
Journal	British Journal of Anaesthesia
Volume	122
Issue number	6
Early online date	25 Oct 2018
DOIs	https://doi.org/10.1016/j.bja.2018.09.019
Publication status	Published - Jun 2019

Keywords

analgesics, opioid
hyperalgesia
opioid-related disorders
pain
pain threshold
Pain Threshold/drug effects
Drug Administration Schedule
Humans
Chronic Pain/drug therapy
Analgesics, Opioid/administration & dosage
Pain Measurement/methods
Hyperalgesia/chemically induced

ASJC Scopus subject areas

Anesthesiology and Pain Medicine

Access to Document

10.1016/j.bja.2018.09.019

Author Accepted ManuscriptAccepted author manuscript, 981 KBLicence: CC BY-NC-ND

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 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.",

keywords = "analgesics, opioid, hyperalgesia, opioid-related disorders, pain, pain threshold, Pain Threshold/drug effects, Drug Administration Schedule, Humans, Chronic Pain/drug therapy, Analgesics, Opioid/administration & dosage, Pain Measurement/methods, Hyperalgesia/chemically induced",

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 = "2019",

month = jun,

doi = "10.1016/j.bja.2018.09.019",

language = "English",

volume = "122",

pages = "e114--e126",

journal = "British Journal of Anaesthesia",

issn = "0007-0912",

publisher = "Elsevier",

number = "6",

}

TY - JOUR

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 - 2019/6

Y1 - 2019/6

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 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.

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 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.

KW - analgesics, opioid

KW - hyperalgesia

KW - opioid-related disorders

KW - pain

KW - pain threshold

KW - Pain Threshold/drug effects

KW - Drug Administration Schedule

KW - Humans

KW - Chronic Pain/drug therapy

KW - Analgesics, Opioid/administration & dosage

KW - Pain Measurement/methods

KW - Hyperalgesia/chemically induced

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DO - 10.1016/j.bja.2018.09.019

M3 - Article

C2 - 30915985

AN - SCOPUS:85055585281

SN - 0007-0912

VL - 122

SP - e114-e126

JO - British Journal of Anaesthesia

JF - British Journal of Anaesthesia

IS - 6

ER -

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

Abstract

Keywords

ASJC Scopus subject areas

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Smith, Blair, FRSE MD MEd FRCGP FHEA FFPMRCA FRCP Edin

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

Abstract

Keywords

ASJC Scopus subject areas

Access to Document

Other files and links

Fingerprint

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Smith, Blair, FRSE MD MEd FRCGP FHEA FFPMRCA FRCP Edin

Cite this