Journal article
Genetic Enhancement of Calcitonin Gene-Related Peptide-Induced Central Sensitization to Mechanical Stimuli in Mice
The journal of pain, Vol.10(9), pp.992-1000
2009
DOI: 10.1016/j.jpain.2009.03.018
PMCID: PMC2752439
PMID: 19628434
Abstract
Calcitonin gene-related peptide (CGRP) is a key player in migraine. To address the role of CGRP in mechanical allodynia, which is a common feature of migraine, we used CGRP-sensitized transgenic mice. These mice have elevated nervous-system expression of the human receptor activity-modifying protein-1 (hRAMP1) subunit of the CGRP receptor. Under baseline conditions, the nestin/hRAMP1 mice and control littermates had similar hindpaw withdrawal thresholds to von Frey filaments. The effect of CGRP was tested using a filament that elicited a withdrawal response on 20% of its presentations. Following intrathecal injection of 1 nmol CGRP in the nestin/hRAMP1 mice, the response frequency was 80% within 30 minutes. The antagonist CGRP(8-37) blocked the increased response. In control littermates, a 5-fold higher dose of CGRP was required to elicit a similar response. In contrast to intrathecal injection, peripheral CGRP did not increase the mechanical responses. Intraplantar injection of capsaicin was used to test the efficacy of endogenous CGRP. Capsaicin increased mechanical responses in the nestin/hRAMP1 and control mice, although a higher dose was required in controls. In contrast to control mice, there was also a contralateral paw response in nestin/hRAMP1 mice, which is consistent with central sensitization.
In this study we show central CGRP-induced mechanical allodynia that is enhanced by overexpression of RAMP1 in nervous system. These data suggest that hypersensitivity to CGRP could be a potential mechanism underlying central sensitization in migraine and point to CGRP-receptor antagonists as a possible therapy for other pain disorders.
Details
- Title: Subtitle
- Genetic Enhancement of Calcitonin Gene-Related Peptide-Induced Central Sensitization to Mechanical Stimuli in Mice
- Creators
- Blanca Marquez de Prado - Department of Molecular Physiology and Biophysics, University of Iowa, Iowa City, IowaDonna L Hammond - Department of Anesthesiology, University of Iowa, Iowa City, IowaAndrew F Russo - Department of Molecular Physiology and Biophysics, University of Iowa, Iowa City, Iowa
- Resource Type
- Journal article
- Publication Details
- The journal of pain, Vol.10(9), pp.992-1000
- DOI
- 10.1016/j.jpain.2009.03.018
- PMID
- 19628434
- PMCID
- PMC2752439
- NLM abbreviation
- J Pain
- ISSN
- 1526-5900
- eISSN
- 1528-8447
- Publisher
- Elsevier Inc
- Language
- English
- Date published
- 2009
- Academic Unit
- Neurology; Molecular Physiology and Biophysics; Iowa Neuroscience Institute; Craniofacial Anomalies Research Center; Nursing; Anesthesia; Neuroscience and Pharmacology
- Record Identifier
- 9984007162402771
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