ArticlePain2009
A possible neural basis for stress-induced hyperalgesia.
Article in Pain, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 58 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.
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.
Who cites it
58 citing papers in PubMed, 1 synthesis or guideline pooled it, 157 citations in OpenAlex.
- 2015 AAHA/AAFP pain management guidelines for dogs and cats.Journal of feline medicine and surgery · 2015Guideline
- Mindfulness-oriented recovery enhancement for chronic pain and prescription opioid misuse: results from an early-stage randomized controlled trial.Journal of consulting and clinical psychology · 2014Trial
- Trial
- Suppression of anger and subsequent pain intensity and behavior among chronic low back pain patients: the role of symptom-specific physiological reactivity.Journal of behavioral medicine · 2012Trial
- The role of mu opioid receptors on excitatory and inhibitory neurons in the rostral ventromedial medulla in neuropathic pain.bioRxiv : the preprint server for biology · 2026Article
- Role of GIRK2 channels in morphine-induced metabolite changes in the rostral ventromedial medulla.Magnetic resonance imaging · 2026Article
- Involvement of the hypothalamus-raphe magnus-spinal defecation center axis in stress-induced defecation in rats.Communications biology · 2026Article
- A JNK-Regulated and IL-1β-Dependent Astrocyte-Neuron Signaling Pathway in the Spinal Dorsal Horn is Essential for Stress-Induced Hyperalgesia.Neural plasticity · 2026Article
- Multi-timescale Rhythmic Dynamics in Rostral Ventromedial Medulla Neurons.bioRxiv : the preprint server for biology · 2025Article
- Blood Sampling in Göttingen Minipigs-A Case Study of Two Standard Methods and Clicker Training as a Restraint-Free Alternative.Animals : an open access journal from MDPI · 2025Article
- The 'in's and out's' of descending pain modulation from the rostral ventromedial medulla.Trends in neurosciences · 2024Review
- The potent analgesia of intrathecal 2R, 6R-HNK via TRPA1 inhibition in LF-PENS-induced chronic primary pain model.The journal of headache and pain · 2023Article
- Direct and Indirect Nociceptive Input from the Trigeminal Dorsal Horn to Pain-Modulating Neurons in the Rostral Ventromedial Medulla.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2023Article
- The Role of The Rostral Ventromedial Medulla in Stress Responses.Brain sciences · 2023Review
- Bulbospinal nociceptive ON and OFF cells related neural circuits and transmitters.Frontiers in pharmacology · 2023Review
- Persistent muscle hyperalgesia after adolescent stress is exacerbated by a mild-nociceptive input in adulthood and is associated with microglia activation.Scientific reports · 2022Article
- Stress, hypoglycemia, and the autonomic nervous system.Autonomic neuroscience : basic & clinical · 2022Review
- Cellular and circuit diversity determines the impact of endogenous opioids in the descending pain modulatory pathway.Frontiers in systems neuroscience · 2022Review
- Shifting the Balance: How Top-Down and Bottom-Up Input Modulate PainFrontiers in pain research (Lausanne, Switzerland) · 2022Review
- D2 Receptors in the Periaqueductal Gray/Dorsal Raphe Modulate Peripheral Inflammatory Hyperalgesia via the Rostral Ventral Medulla.Neuroscience · 2021Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
3 authors at 2 institutions in 1 country.
Funding
Abstract
Intense stress and fear have long been known to give rise to a suppression of pain termed "stress-induced analgesia", mediated by brainstem pain-modulating circuitry, including pain-inhibiting neurons of the rostral ventromedial medulla. However, stress does not invariably suppress pain, and indeed, may exacerbate it. Although there is a growing support for the idea of "stress-induced hyperalgesia", the neurobiological basis for this effect remains almost entirely unknown. Using simultaneous single-cell recording and functional analysis, we show here that stimulation of the dorsomedial nucleus of the hypothalamus, known to be a critical component of central mechanisms mediating neuroendocrine, cardiovascular and thermogenic responses to mild or "emotional" stressors such as air puff, also triggers thermal hyperalgesia by recruiting pain-facilitating neurons, "ON-cells", in the rostral ventromedial medulla. Activity of identified RVM ON-cells, OFF-cells and NEUTRAL cells, nociceptive withdrawal thresholds, rectal temperature, and heart rate were recorded in lightly anesthetized rats. In addition to the expected increases in body temperature and heart rate, disinhibition of the DMH induced a robust activation of ON-cells, suppression of OFF-cell firing and behavioral hyperalgesia. Blocking ON-cell activation prevented hyperalgesia, but did not interfere with DMH-induced thermogenesis or tachycardia, pointing to differentiation of neural substrates for autonomic and nociceptive modulation within the RVM. These data demonstrate a top-down activation of brainstem pain-facilitating neurons, and suggest a possible neural circuit for stress-induced hyperalgesia.
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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.