Journal article
Heat hyperalgesia and mechanical hypersensitivity induced by calcitonin gene-related peptide in a mouse model of neurofibromatosis
PloS one, Vol.9(9), pp.e106767-e106767
2014
DOI: 10.1371/journal.pone.0106767
PMCID: PMC4153688
PMID: 25184332
Abstract
This study examined whether mice with a deficiency of neurofibromin, a Ras GTPase activating protein, exhibit a nociceptive phenotype and probed a possible contribution by calcitonin gene-related peptide. In the absence of inflammation, Nf1+/- mice (B6.129S6 Nf1/J) and wild type littermates responded comparably to heat or mechanical stimuli, except for a subtle enhanced mechanical sensitivity in female Nf1+/- mice. Nociceptive phenotype was also examined after inflammation induced by capsaicin and formalin, which release endogenous calcitonin gene-related peptide. Intraplantar injection of capsaicin evoked comparable heat hyperalgesia and mechanical hypersensitivity in Nf1+/- and wild type mice of both genders. Formalin injection caused a similar duration of licking in male Nf1+/- and wild type mice. Female Nf1+/- mice licked less than wild type mice, but displayed other nociceptive behaviors. In contrast, intraplantar injection of CGRP caused greater heat hyperalgesia in Nf1+/- mice of both genders compared to wild type mice. Male Nf1+/- mice also exhibited greater mechanical hypersensitivity; however, female Nf1+/- mice exhibited less mechanical hypersensitivity than their wild type littermates. Transcripts for calcitonin gene-related peptide were similar in the dorsal root ganglia of both genotypes and genders. Transcripts for receptor activity-modifying protein-1, which is rate-limiting for the calcitonin gene-related peptide receptor, in the spinal cord were comparable for both genotypes and genders. The increased responsiveness to intraplantar calcitonin gene-related peptide suggests that the peripheral actions of calcitonin gene-related peptide are enhanced as a result of the neurofibromin deficit. The analgesic efficacy of calcitonin gene-related peptide receptor antagonists may therefore merit investigation in neurofibromatosis patients.
Details
- Title: Subtitle
- Heat hyperalgesia and mechanical hypersensitivity induced by calcitonin gene-related peptide in a mouse model of neurofibromatosis
- Creators
- Stephanie White - University of IowaBlanca Marquez de Prado - Department of Anesthesia, University of Iowa, Iowa City, Iowa, United States of America; Department of Molecular Physiology and Biophysics, University of Iowa, Iowa City, Iowa, United States of AmericaAndrew F Russo - Department of Molecular Physiology and Biophysics, University of Iowa, Iowa City, Iowa, United States of AmericaDonna L Hammond - Department of Anesthesia, University of Iowa, Iowa City, Iowa, United States of America; Department of Pharmacology, University of Iowa, Iowa City, Iowa, United States of America
- Resource Type
- Journal article
- Publication Details
- PloS one, Vol.9(9), pp.e106767-e106767
- DOI
- 10.1371/journal.pone.0106767
- PMID
- 25184332
- PMCID
- PMC4153688
- NLM abbreviation
- PLoS One
- ISSN
- 1932-6203
- eISSN
- 1932-6203
- Publisher
- Public Library of Science; United States
- Grant note
- R01 NS075599 / NINDS NIH HHS
- Language
- English
- Date published
- 2014
- Academic Unit
- Neurology; Molecular Physiology and Biophysics; Iowa Neuroscience Institute; Craniofacial Anomalies Research Center; Anesthesia; Neuroscience and Pharmacology; Internal Medicine
- Record Identifier
- 9984006365202771
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