Evidence map›Paper›PMID 33180816›Full record

Trial reportPloS one2020

High-dose naloxone: Effects by late administration on pain and hyperalgesia following a human heat injury model. A randomized, double-blind, placebo-controlled, crossover trial with an enriched enrollment design.

Anders Deichmann Springborg, Elisabeth Kjær Jensen, Mads Kreilgaard, Morten Aagaard Petersen, Theodoros Papathanasiou, Trine Meldgaard Lund, Bradley Kenneth Taylor, Mads Utke Werner

Open access · goldAbstract readRandomized Controlled Trial
In one paragraph

Trial report in PloS one, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed
0.6field-weighted citation impact, top 32% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

6 citing papers in PubMed, 11 citations in OpenAlex.

  1. Review
  2. Review
  3. Article
  4. Review
  5. French-Canadian Translation and Cultural Adaptation of the Clinical Opiate Withdrawal Scale: The COWS-FC.Canadian journal of psychiatry. Revue canadienne de psychiatrie · 2022
    Article
  6. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

8 authors at 4 institutions in 3 countries.

Anders Deichmann SpringborgNeuroscience Center, Copenhagen University Hospitals, Copenhagen, Denmark.ORCID 0000-0003-2203-7050
Elisabeth Kjær JensenNeuroscience Center, Copenhagen University Hospitals, Copenhagen, Denmark.
Mads KreilgaardDepartment of Drug Design and Pharmacology, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
Morten Aagaard PetersenThe Research Unit, Department of Palliative Medicine, Copenhagen University Hospitals, Copenhagen, Denmark.
Theodoros PapathanasiouDepartment of Drug Design and Pharmacology, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
Trine Meldgaard LundDepartment of Drug Design and Pharmacology, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.ORCID 0000-0001-8598-2880
Bradley Kenneth TaylorDepartment of Anesthesiology, Pittsburgh Center for Pain Research, and the Pittsburgh Project to End Opioid Misuse, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America.
Mads Utke WernerNeuroscience Center, Copenhagen University Hospitals, Copenhagen, Denmark.
Copenhagen University Hospital · DKUniversity of Copenhagen · DKLund University · SEUniversity of Pittsburgh · US

Funding

Long-term activation of spinal opioid analgesia after inflammationR01DA037621 · NIDA · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI TAYLOR, BRADLEY K. · 2015 to 2019
$3.4M
NIDA NIH HHS R01 DA037621
6 · The paper itself

Abstract

Severe chronic postsurgical pain has a prevalence of 4-10% in the surgical population. The underlying nociceptive mechanisms have not been well characterized. Following the late resolution phase of an inflammatory injury, high-dose μ-opioid-receptor inverse agonists reinstate hypersensitivity to nociceptive stimuli. This unmasking of latent pain sensitization has been a consistent finding in rodents while only observed in a limited number of human volunteers. Latent sensitization could be a potential triggering venue in chronic postsurgical pain. The objective of the present trial was in detail to examine the association between injury-induced secondary hyperalgesia and naloxone-induced unmasking of latent sensitization. Healthy volunteers (n = 80) received a cutaneous heat injury (47°C, 420 s, 12.5 cm2). Baseline secondary hyperalgesia areas were assessed 1 h post-injury. Utilizing an enriched enrollment design, subjects with a magnitude of secondary hyperalgesia areas in the upper quartile ('high-sensitizers' [n = 20]) and the lower quartile ('low-sensitizers' [n = 20]) were selected for further study. In four consecutive experimental sessions (Sessions 1 to 4), the subjects at two sessions (Sessions 1 and 3) received a cutaneous heat injury followed 168 h later (Sessions 2 and 4) by a three-step target-controlled intravenous infusion of naloxone (3.25 mg/kg), or normal saline. Assessments of secondary hyperalgesia areas were made immediately before and stepwise during the infusions. Simple univariate statistics revealed no significant differences in secondary hyperalgesia areas between naloxone and placebo treatments (P = 0.215), or between 'high-sensitizers' and 'low-sensitizers' (P = 0.757). In a mixed-effects model, secondary hyperalgesia areas were significantly larger following naloxone as compared to placebo for 'high-sensitizers' (P < 0.001), but not 'low-sensitizers' (P = 0.651). Although we could not unequivocally demonstrate naloxone-induced reinstatement of heat injury-induced hyperalgesia, further studies in clinical postsurgical pain models are warranted.

Indexed as

Hot TemperatureHumansHyperalgesiaInfusions, IntravenousMaleNaloxoneNarcotic AntagonistsNociceptionPainYoung AdultNaloxoneNarcotic Antagonists

Identifiers

PMID33180816
PMCPMC7660513
OpenAlexW3101849764

What OpenQuestion holds

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LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.