ArticlePain2020
Repetitive stress in mice causes migraine-like behaviors and calcitonin gene-related peptide-dependent hyperalgesic priming to a migraine trigger.
Article in Pain, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
48 citing papers in PubMed, 2 syntheses or guidelines pooled it, 114 citations in OpenAlex.
- Sleep macro- and microstructure in migraine and cluster headache: a systematic review of objective assessments.The journal of headache and pain · 2026Pooled it
- An underrepresented majority: A systematic review utilizing allodynic criteria to examine the present scarcity of discrete animal models for episodic migraine.Cephalalgia : an international journal of headache · 2021Pooled it
- Early life stress induces brain-wide electrical network predisposition to migraine.The journal of headache and pain · 2026Article
- From bench to bedside: relevant animal models across the migraine attack phases.The journal of headache and pain · 2026Review
- Masticatory myalgia to headache-like secondary hypersensitivity induces gene plasticity at dura mater.The journal of headache and pain · 2026Article
- MRGPRX2 as a novel therapeutic target in headache.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2026Review
- Light-aversion and cephalic allodynia in an intravenous CGRP model of migraine-like behaviour in male and female rats.The journal of headache and pain · 2026Article
- Restraint stress prolongs Diestrus phase of mouse Estrous cycle.Oxford open neuroscience · 2026Article
- Macrophages and iNOS contribute to the effects of dural prolactin and repeated stress in mouse migraine models.The journal of headache and pain · 2025Article
- Symptoms of allodynia and pain thresholds amongst those with acute post-traumatic headache attributed to mild traumatic brain injury: a prospective, longitudinal study.The journal of headache and pain · 2025Article
- Restraint Stress Prolongs Diestrus Phase of Mouse Estrous Cycle.bioRxiv : the preprint server for biology · 2025Article
- Symptoms of Allodynia and Pain Thresholds Amongst Those with Acute Post-Traumatic Headache Attributed to Mild Traumatic Brain Injury: A Prospective, Longitudinal Study.Research square · 2025Article
- Oral atogepant mitigates spreading depolarization-induced pain and anxiety behavior in mice.The journal of headache and pain · 2025Article
- Sex differences in the transition to chronic pain.The Journal of clinical investigation · 2025Review
- The role and interaction of hypothalamic-related neurotransmitters in migraine.The journal of headache and pain · 2025Review
- Meningeal K ATP channels contribute to behavioral responses in preclinical migraine models.Pain · 2025Article
- Sex differences in the effects of calcitonin gene-related peptide signaling on migraine-like behavior in animal models: a narrative review.Frontiers in neurology · 2025Review
- Disentangling sex-specific mechanisms in neuropathic and nociplastic chronic pain: a review.Frontiers in neurology · 2025Review
- Harnessing Miniscope Imaging in Freely Moving Animals to Unveil Migraine Pathophysiology and Validate Novel Therapeutic Strategies.Synapse (New York, N.Y.) · 2024Review
- Effects of Stress Exposure to Pain Perception in Pre-Clinical Studies: Focus on the Nociceptin/Orphanin FQ-NOP Receptor System.Brain sciences · 2024Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
12 authors at 3 institutions in 1 country.
Funding
Abstract
Migraine is one of the most disabling disorders worldwide but the underlying mechanisms are poorly understood. Stress is consistently reported as a common trigger of migraine attacks. Here, we show that repeated stress in mice causes migraine-like behaviors that are responsive to a migraine therapeutic. Adult female and male mice were exposed to 2 hours of restraint stress for 3 consecutive days, after which they demonstrated facial mechanical hypersensitivity and facial grimace responses that were resolved by 14 days after stress. Hypersensitivity or grimace was not observed in either control animals or those stressed for only 1 day. After return to baseline, the nitric oxide donor sodium nitroprusside (SNP; 0.1 mg/kg) elicited mechanical hypersensitivity in stressed but not in control animals, demonstrating the presence of hyperalgesic priming. This suggests the presence of a migraine-like state, because nitric oxide donors are reliable triggers of attacks in migraine patients but not controls. The stress paradigm also caused priming responses to dural pH 7.0 treatment. The presence of this primed state after stress is not permanent because it was no longer present at 35 days after stress. Finally, mice received either the calcitonin gene-related peptide monoclonal antibody ALD405 (10 mg/kg) 24 hours before SNP or a coinjection of sumatriptan (0.6 mg/kg). ALD405, but not sumatriptan, blocked the facial hypersensitivity due to SNP. This stress paradigm in mice and the subsequent primed state caused by stress allow further preclinical investigation of mechanisms contributing to migraine, particularly those caused by common triggers of attacks.
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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.