ArticlePain2018
Peripherally administered calcitonin gene-related peptide induces spontaneous pain in mice: implications for migraine.
Article in Pain, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 57 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
57 citing papers in PubMed, 2 syntheses or guidelines pooled it, 98 citations in OpenAlex.
- Administration of meloxicam to improve the welfare of mice in research: a systematic review (2000 - 2020).Veterinary research communications · 2022Pooled 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
- Calcitonin gene-related peptide induces headache attacks in people with idiopathic intracranial hypertension.Brain : a journal of neurology · 2026Trial
- Article
- 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
- Glymphatic function restored by α1-noradrenergic antagonism alleviates headache allodynia in mice.bioRxiv : the preprint server for biology · 2026Article
- Neuro-Immune Crosstalk: Molecular Mechanisms, Biological Functions, Diseases, and Therapeutic Targets.MedComm · 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
- Article
- Article
- PACAP versus CGRP in migraine: From mouse models to clinical translation.Cephalalgia : an international journal of headache · 2025Review
- Pretreatment with an anti-CGRP monoclonal antibody attenuates mild TBI-induced tactile hypersensitivity in mice.The journal of headache and pain · 2025Article
- Activation of δ-opioid receptors blocks allodynia in a model of headache induced by PACAP.British journal of pharmacology · 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
- An Automated Squint Method for Time-syncing Behavior and Brain Dynamics in Mouse Pain Studies.Journal of visualized experiments : JoVE · 2024Article
- Meningeal brain borders and migraine headache genesis.Trends in neurosciences · 2024Review
- Molecular nociceptive mechanisms in migraine: The migraine cascade.European journal of neurology · 2024Review
- A Vestibular Challenge Combined with Calcitonin Gene-Related Peptide (CGRP) Promotes Anxiety-Like Behaviors.eNeuro · 2024Article
- Rare GPR37L1 Variants Reveal Potential Association between GPR37L1 and Disorders of Anxiety and Migraine.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2024Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
16 authors at 3 institutions in 1 country.
Funding
Abstract
Migraine is the third most common disease in the world (behind dental caries and tension-type headache) with an estimated global prevalence of 15%, yet its etiology remains poorly understood. Recent clinical trials have heralded the potential of therapeutic antibodies that block the actions of the neuropeptide calcitonin gene-related peptide (CGRP) or its receptor to prevent migraine. Calcitonin gene-related peptide is believed to contribute to trigeminal nerve hypersensitivity and photosensitivity in migraine, but a direct role in pain associated with migraine has not been established. In this study, we report that peripherally administered CGRP can act in a light-independent manner to produce spontaneous pain in mice that is manifested as a facial grimace. As an objective validation of the orbital tightening action unit of the grimace response, we developed a squint assay using a video-based measurement of the eyelid fissure, which confirmed a significant squint response after CGRP injection, both in complete darkness and very bright light. These indicators of discomfort were completely blocked by preadministration of a monoclonal anti-CGRP-blocking antibody. However, the nonsteroidal anti-inflammatory drug meloxicam failed to block the effect of CGRP. Interestingly, an apparent sex-specific response to treatment was observed with the antimigraine drug sumatriptan partially blocking the CGRP response in male, but not female mice. These results demonstrate that CGRP can induce spontaneous pain, even in the absence of light, and that the squint response provides an objective biomarker for CGRP-induced pain that is translatable to humans.
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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.