Peripherally administered calcitonin gene-related peptide induces spontaneous pain in mice: implications for migraine.

Autor:	Rea BJ; Department of Molecular Physiology and Biophysics, University of Iowa Carver College of Medicine, University of Iowa, Iowa City, IA, United States., Wattiez AS; Department of Molecular Physiology and Biophysics, University of Iowa Carver College of Medicine, University of Iowa, Iowa City, IA, United States.; Center for the Prevention and Treatment of Visual Loss, Iowa VA Medical Center, Iowa City, IA, United States., Waite JS; Department of Molecular Physiology and Biophysics, University of Iowa Carver College of Medicine, University of Iowa, Iowa City, IA, United States., Castonguay WC; Department of Molecular Physiology and Biophysics, University of Iowa Carver College of Medicine, University of Iowa, Iowa City, IA, United States., Schmidt CM; Department of Molecular Physiology and Biophysics, University of Iowa Carver College of Medicine, University of Iowa, Iowa City, IA, United States., Fairbanks AM; Department of Molecular Physiology and Biophysics, University of Iowa Carver College of Medicine, University of Iowa, Iowa City, IA, United States., Robertson BR; Department of Molecular Physiology and Biophysics, University of Iowa Carver College of Medicine, University of Iowa, Iowa City, IA, United States., Brown CJ; Department of Molecular Physiology and Biophysics, University of Iowa Carver College of Medicine, University of Iowa, Iowa City, IA, United States., Mason BN; Department of Molecular and Cellular Biology Program, University of Iowa Carver College of Medicine, University of Iowa, Iowa City, IA, United States., Moldovan-Loomis MC; Alder BioPharmaceuticals, Inc, Bothell, WA, United States., Garcia-Martinez LF; Alder BioPharmaceuticals, Inc, Bothell, WA, United States., Poolman P; Center for the Prevention and Treatment of Visual Loss, Iowa VA Medical Center, Iowa City, IA, United States.; Department of Ophthalmology and Visual Sciences, University of Iowa Carver College of Medicine, University of Iowa, Iowa City, IA, United States., Ledolter J; Center for the Prevention and Treatment of Visual Loss, Iowa VA Medical Center, Iowa City, IA, United States.; Department of Statistics and Actuarial Sciences, Tippie College of Business, University of Iowa, Iowa City, IA, United States., Kardon RH; Center for the Prevention and Treatment of Visual Loss, Iowa VA Medical Center, Iowa City, IA, United States.; Department of Ophthalmology and Visual Sciences, University of Iowa Carver College of Medicine, University of Iowa, Iowa City, IA, United States., Sowers LP; Department of Molecular Physiology and Biophysics, University of Iowa Carver College of Medicine, University of Iowa, Iowa City, IA, United States.; Center for the Prevention and Treatment of Visual Loss, Iowa VA Medical Center, Iowa City, IA, United States., Russo AF; Department of Molecular Physiology and Biophysics, University of Iowa Carver College of Medicine, University of Iowa, Iowa City, IA, United States.; Center for the Prevention and Treatment of Visual Loss, Iowa VA Medical Center, Iowa City, IA, United States.; Department of Neurology, University of Iowa Carver College of Medicine, University of Iowa, Iowa City, IA, United States.
Jazyk:	angličtina
Zdroj:	Pain [Pain] 2018 Nov; Vol. 159 (11), pp. 2306-2317.
DOI:	10.1097/j.pain.0000000000001337
Abstrakt:	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.
Databáze:	MEDLINE
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