Variable Sensitivity to Noxious Heat Is Mediated by Differential Expression of the CGRP Gene

Heat sensitivity shows considerable functional variability in humans and laboratory animals, and is fundamental to inflammatory and possibly neuropathic pain. In the mouse, at least, much of this variability is genetic because inbred strains differ robustly in their behavioral sensitivity to noxious...

Full description

Saved in:
Bibliographic Details
Published inProceedings of the National Academy of Sciences - PNAS Vol. 102; no. 36; pp. 12938 - 12943
Main Authors Mogil, Jeffrey S., Miermeister, Frank, Seifert, Frank, Strasburg, Kate, Zimmermann, Katharina, Reinold, Heiko, Austin, Jean-Sebastien, Bernardini, Nadia, Chesler, Elissa J., Hofmann, Heiko A., Hordo, Christian, Messlinger, Karl, Kumar V. S. Nemmani, Rankin, Andrew L., Ritchie, Jennifer, Siegling, Angela, Smith, Shad B., Sotocinal, Susana, Vater, Axel, Lehto, Sonya G., Klussmann, Sven, Quirion, Remi, Michaelis, Martin, Devor, Marshall, Reeh, Peter W., McEwen, Bruce S.
Format Journal Article
LanguageEnglish
Published United States National Academy of Sciences 06.09.2005
National Acad Sciences
Subjects
Animals
BASIC BIOLOGICAL SCIENCES
Biological Sciences
Calcitonin gene related peptide receptors
Calcitonin Gene-Related Peptide - genetics
Chromosomes
Electrophysiology
Female
FUNCTIONALS
Gene expression
Gene Expression Regulation
GENES
Genetic linkage
GENETICS
Heat
Hot Temperature - adverse effects
Hyperalgesia
INACTIVATION
Inbred strains
LABORATORY ANIMALS
Male
Mice
Mice, Inbred Strains
Neurology
Nociceptors
Nociceptors - metabolism
Pain
Pain Measurement
Pain Threshold - physiology
Peptides
SENSITIVITY
Sensitization
Skin
Species Specificity
STIMULI
STRAINS
Online AccessGet full text

Cover

More Information
Summary:Heat sensitivity shows considerable functional variability in humans and laboratory animals, and is fundamental to inflammatory and possibly neuropathic pain. In the mouse, at least, much of this variability is genetic because inbred strains differ robustly in their behavioral sensitivity to noxious heat. These strain differences are shown here to reflect differential responsiveness of primary afferent thermal nociceptors to heat stimuli. We further present convergent behavioral and electrophysiological evidence that the variable responses to noxious heat are due to strain-dependence of CGRP expression and sensitivity. Strain differences in behavioral response to noxious heat could be abolished by peripheral injection of CGRP, blockade of cutaneous and spinal CGRP receptors, or long-term inactivation of CGRP with a CGRP-binding Spiegelmer. Linkage mapping supports the contention that the genetic variant determining variable heat pain sensitivity across mouse strains affects the expression of the Calca gene that codes for CGRPα.
Bibliography:ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
content type line 23
DE-AC05-00OR22725
USDOE Office of Science (SC)
To whom correspondence should be sent at the present address: Institute of Physiology and Pathophysiology, University Erlangen-Nuremberg, D-91054 Erlangen, Germany. E-mail: reeh@physiologie1.uni-erlangen.de.
Author contributions: J.S.M., M.D., and P.W.R. designed research; J.S.M., F.M., F.S., K.S., K.Z., H.R., J.-S.A., N.B., H.A.H., C.H., K.V.S.N., A.L.R., J.R., A.S., S.B.S., S.S., S.G.L., M.M., and P.W.R. performed research; K.M., A.V., S.K., and R.Q. contributed new reagents/analytic tools; J.S.M., E.J.C., and P.W.R. analyzed data; and J.S.M., R.Q., M.D., and P.W.R. wrote the paper.
This paper was submitted directly (Track II) to the PNAS office.
Edited by Bruce S. McEwen, The Rockefeller University, New York, NY, and approved July 26, 2005
Abbreviations: CGRP, calcitonin gene-related peptide; iCGRP, immunoreactive CGRP; DRG, dorsal root ganglion; PWL, paw-withdrawal latency.
F.M., F. S., K.S., K.Z., and H.R. contributed equally to this work.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.0503264102