ArticlePloS one2015
Endogenous Opioid-Masked Latent Pain Sensitization: Studies from Mouse to Human.
Article in PloS one, 2015. 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 27 papers, 1 of them a synthesis 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
27 citing papers in PubMed, 1 synthesis or guideline pooled it, 54 citations in OpenAlex.
- Methodology and applicability of the human contact burn injury model: A systematic review.PloS one · 2021Pooled it
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- The pharmacotherapeutic potential of neuropeptide Y for chronic pain.Journal of internal medicine · 2025Review
- Neuropeptide Y Y2 receptors in acute and chronic pain and itch.Neuropeptides · 2024Review
- Neuropeptide Y Y2 Receptors in Sensory Neurons Tonically Suppress Nociception and Itch but Facilitate Postsurgical and Neuropathic Pain Hypersensitivity.Anesthesiology · 2024Article
- The mechanisms and management of persistent postsurgical pain.Frontiers in pain research (Lausanne, Switzerland) · 2023Review
- HDAC6 Inhibition Reverses Cisplatin-Induced Mechanical Hypersensitivity via Tonic Delta Opioid Receptor Signaling.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2022Article
- Postsurgical Latent Pain Sensitization Is Driven by Descending Serotonergic Facilitation and Masked by µ-Opioid Receptor Constitutive Activity in the Rostral Ventromedial Medulla.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2022Article
- Developmental mechanisms of CPSP: Clinical observations and translational laboratory evaluations.Canadian journal of pain = Revue canadienne de la douleur · 2022Review
- Sex Differences in Protein Kinase A Signaling of the Latent Postoperative Pain Sensitization That Is Masked by Kappa Opioid Receptors in the Spinal Cord.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2021Article
- Sex differences in kappa opioid receptor inhibition of latent postoperative pain sensitization in dorsal horn.Neuropharmacology · 2020Article
- 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
- Morphine immunomodulation prolongs inflammatory and postoperative pain while the novel analgesic ZH853 accelerates recovery and protects against latent sensitization.Journal of neuroinflammation · 2019Article
- Opioid receptors inhibit the spinal AMPA receptor CaExperimental neurology · 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
- Subliminal (latent) processing of pain and its evolution to conscious awareness.Neuroscience and biobehavioral reviews · 2018Review
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 2 institutions in 2 countries.
Funding
Abstract
unlabelledFollowing the resolution of a severe inflammatory injury in rodents, administration of mu-opioid receptor inverse agonists leads to reinstatement of pain hypersensitivity. The mechanisms underlying this form of latent pain sensitization (LS) likely contribute to the development of chronic pain, but LS has not yet been demonstrated in humans. Using a C57BL/6 mouse model of cutaneous mild heat injury (MHI) we demonstrated a dose-dependent reinstatement of pain sensitization, assessed as primary (P < 0.001) and secondary hyperalgesia (P < 0.001) by naloxone (0.3–10 mg/kg), 168 hrs after the induction of MHI. Forward-translating the dose data to a human MHI model (n = 12) we could show that LS does indeed occur after naloxone 2 mg/kg, 168 hrs after a MHI. Our previous unsuccessful efforts to demonstrate unmasking of LS in humans are thus likely explained by an insufficient naloxone dose (0.021 mg/kg). However, while LS was consistently demonstrated in 21/24 mice, LS was only seen in 4/12 subjects. This difference is likely due to selection bias since the C57BL/6 mouse strain exhibits markedly enhanced pain sensitivity in assays of acute thermal nociception. Future exploratory studies in humans should prioritize inclusion of “high-sensitizers” prone to develop LS and use post-surgical models to elucidate markers of vulnerability to chronic postsurgical pain.
trial registrationEudraCT 2012-005663-27.
Indexed as
Identifiers
What OpenQuestion holds
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.