Journal article
Peripherally administered calcitonin gene-related peptide induces spontaneous pain in mice: Implications for migraine
Pain, Vol.159(11), pp.2306-2317
2018
DOI: 10.1097/j.pain.0000000000001337
PMID: 29994995
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.
Details
- Title: Subtitle
- Peripherally administered calcitonin gene-related peptide induces spontaneous pain in mice: Implications for migraine
- Creators
- Brandon J ReaAnne Sophie WattiezJayme S WaiteWilliam C CastonguayChantel M SchmidtAaron M FairbanksBennett R RobertsonCameron J Brown - University of IowaLevi P SowersAndrew F RussoPieter PoolmanJohannes LedolterRandy H KardonBianca N MasonMaria Cristina Moldovan-LoomisLeon F Garcia-Martinez
- Resource Type
- Journal article
- Publication Details
- Pain, Vol.159(11), pp.2306-2317
- DOI
- 10.1097/j.pain.0000000000001337
- PMID
- 29994995
- NLM abbreviation
- Pain
- ISSN
- 0304-3959
- eISSN
- 1872-6623
- Language
- English
- Date published
- 2018
- Academic Unit
- Statistics and Actuarial Science; Neurology; Molecular Physiology and Biophysics; Stead Family Department of Pediatrics; Iowa Neuroscience Institute; Craniofacial Anomalies Research Center; Business Analytics; Neurology (Pediatrics); Ophthalmology and Visual Sciences
- Record Identifier
- 9983985823002771
Metrics
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