ArticlePloS one2014
An improved model of heat-induced hyperalgesia--repetitive phasic heat pain causing primary hyperalgesia to heat and secondary hyperalgesia to pinprick and light touch.
Article in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers, 1 of them a synthesis that pooled it.
What it found
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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.
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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.
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Who cites it
18 citing papers in PubMed, 1 synthesis or guideline pooled it, 40 citations in OpenAlex.
- Human surrogate models of central sensitization: A critical review and practical guide.European journal of pain (London, England) · 2021Pooled it
- The Effect ofNutrients · 2026Trial
- Presenting a sham treatment as personalised increases the placebo effect in a randomised controlled trial.eLife · 2023Trial
- Trial
- Placebo Effect on Pain-Related Autonomic Responses in a State of Experimentally-Induced Sensitization.European journal of pain (London, England) · 2026Observational
- Nocebo Effect on Pain-Related Autonomic Responses in a State of Experimentally-Induced Sensitization.European journal of pain (London, England) · 2025Article
- Article
- Assessing signs of central sensitization: A critical review of physiological measures in experimentally induced secondary hyperalgesia.European journal of pain (London, England) · 2025Review
- Article
- Priming of the autonomic nervous system after an experimental human pain model.Journal of neurophysiology · 2023Article
- Pain Experience and Sensory Changes in Astronauts During and After Short-Lasting Commercial Spaceflight: A Proof-of-Concept Study.Journal of pain research · 2023Article
- Signaling via the FLP-14/FRPR-19 neuropeptide pathway sustains nociceptive response to repeated noxious stimuli in C. elegans.PLoS genetics · 2021Article
- A Novel Diagnostic Test for End-Stage Sensory Failure Associated With Diabetic Foot Ulceration: Proof-of-Principle Study.Journal of diabetes science and technology · 2021Article
- Article
- Reliability of temporal summation, thermal and pressure pain thresholds in a healthy cohort and musculoskeletal trauma population.PloS one · 2020Article
- Pain catastrophizing may moderate the association between pain and secondary hyperalgesia.Journal of applied biobehavioral research · 2017Article
- Functional magnetic resonance imaging of the cervical spinal cord during thermal stimulation across consecutive runs.NeuroImage · 2016Article
- Article
Corrections and comments
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Authors and funding
5 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
This study tested a modified experimental model of heat-induced hyperalgesia, which improves the efficacy to induce primary and secondary hyperalgesia and the efficacy-to-safety ratio reducing the risk of tissue damage seen in other heat pain models. Quantitative sensory testing was done in eighteen healthy volunteers before and after repetitive heat pain stimuli (60 stimuli of 48°C for 6 s) to assess the impact of repetitive heat on somatosensory function in conditioned skin (primary hyperalgesia area) and in adjacent skin (secondary hyperalgesia area) as compared to an unconditioned mirror image control site. Additionally, areas of flare and secondary hyperalgesia were mapped, and time course of hyperalgesia determined. After repetitive heat pain conditioning we found significant primary hyperalgesia to heat, and primary and secondary hyperalgesia to pinprick and to light touch (dynamic mechanical allodynia). Acetaminophen (800 mg) reduced pain to heat or pinpricks only marginally by 11% and 8%, respectively (n.s.), and had no effect on heat hyperalgesia. In contrast, the areas of flare (-31%) and in particular of secondary hyperalgesia (-59%) as well as the magnitude of hyperalgesia (-59%) were significantly reduced (all p<0.001). Thus, repetitive heat pain induces significant peripheral sensitization (primary hyperalgesia to heat) and central sensitization (punctate hyperalgesia and dynamic mechanical allodynia). These findings are relevant to further studies using this model of experimental heat pain as it combines pronounced peripheral and central sensitization, which makes a convenient model for combined pharmacological testing of analgesia and anti-hyperalgesia mechanisms related to thermal and mechanical input.
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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.