Trial reportPloS one2013
Does naloxone reinstate secondary hyperalgesia in humans after resolution of a burn injury? A placebo-controlled, double-blind, randomized, cross-over study.
Trial report in PloS one, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 2 registered trials, which are not on this map. Cited by 14 papers, 2 of them syntheses that pooled 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.
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.
Effect of High-dose Target-controlled Naloxone Infusion on Pain and Hyperalgesia During a Burn Injury. A Randomized, Placebo-controlled, Double-blind Crossover Study
Effect of High-dose Target-controlled Naloxone Infusion on Pain and Hyperal-gesia in Patients Following Recovery From Impacted Mandibular Third Molar Extraction. A Randomized, Placebo-controlled, Double-blind Crossover Study.
Who cites it
14 citing papers in PubMed, 2 syntheses or guidelines pooled it, 20 citations in OpenAlex.
- Methodology and applicability of the human contact burn injury model: A systematic review.PloS one · 2021Pooled it
- Endogenous opioid antagonism in physiological experimental pain models: a systematic review.PloS one · 2015Pooled it
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- Is heat pain detection threshold associated with the area of secondary hyperalgesia following brief thermal sensitization? A study of healthy volunteers - design and detailed plan of analysis.BMC anesthesiology · 2016Trial
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- Tissue damage-induced axon injury-associated responses in sensory neurons: requirements, prevention, and potential role in persistent post-surgical pain.Frontiers in pain research (Lausanne, Switzerland) · 2025Article
- Recent advances toward understanding the mysteries of the acute to chronic pain transition.Current opinion in physiology · 2019Article
- High-dose naloxone, an experimental tool uncovering latent sensitisation: pharmacokinetics in humans.British journal of anaesthesia · 2019Article
- Article
- Corticotropin-Releasing Factor in the Brain and Blocking Spinal Descending Signals Induce Hyperalgesia in the Latent Sensitization Model of Chronic Pain.Neuroscience · 2018Article
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- Management of persistent postsurgical inguinal pain.Langenbeck's archives of surgery · 2014Review
- Endogenous analgesia, dependence, and latent pain sensitization.Current topics in behavioral neurosciencesArticle
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 3 institutions in 2 countries.
Funding
Abstract
introductionDevelopment of secondary hyperalgesia following a cutaneous injury is a centrally mediated, robust phenomenon. The pathophysiological role of endogenous opioid signalling to the development of hyperalgesia is unclear. Recent animal studies, carried out after the resolution of inflammatory pain, have demonstrated reinstatement of tactile hypersensitivity following administration of μ-opioid-receptor-antagonists. In the present study in humans, we analyzed the effect of naloxone when given after the resolution of secondary hyperalgesia following a first-degree burn injury.
methodsTwenty-two healthy volunteers were included in this placebo-controlled, randomized, double-blind, cross-over study. Following baseline assessment of thermal and mechanical thresholds, a first-degree burn injury (BI; 47°C, 7 minutes, thermode area 12.5 cm(2)) was induced on the lower leg. Secondary hyperalgesia areas around the BI-area, and separately produced by brief thermal sensitization on the contralateral thigh (BTS; 45°C, 3 minutes, area 12.5 cm(2)), were assessed using a polyamide monofilament at pre-BI and 1, 2, and 3 hours post-BI. At 72 hrs, BI and BTS secondary hyperalgesia areas were assessed prior to start of a 30 minutes intravenous infusion of naloxone (total dose 21 microg/kg) or placebo. Fifteen minutes after start of the infusion, BI and BTS secondary hyperalgesia areas were reassessed, along with mechanical and thermal thresholds.
resultsSecondary hyperalgesia areas were demonstrable in all volunteers 1-3 hrs post-BI, but were not demonstrable at 72 hrs post-burn in 73-86% of the subjects. Neither magnitude of secondary hyperalgesia areas nor the mechanical and thermal thresholds were associated with naloxone-treated compared to placebo-treated subjects.
conclusionNaloxone (21 microg/kg) did not reinstate secondary hyperalgesia when administered 72 hours after a first-degree burn injury and did not increase BTS-generated hyperalgesia. The negative results may be due to the low dose of naloxone or insufficient tissue injury to generate latent sensitization.
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Registered trials
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.