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Variable sensitivity to noxious heat is mediated by differential expression of the CGRP gene
Open accessAbstract
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.
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Cited by
Calcitonin Gene-Related Peptide: Physiology and Pathophysiology
Russell, F. A., King, R., Smillie, S.-J., Kodji, X., & Brain, S. D. (2014) · Physiological Reviews · doi:10.1152/physrev.00034.2013 · Cited by 1,258
Animal models of pain: progress and challenges
Mogil, J. S. (2009) · Nature Reviews Neuroscience · doi:10.1038/nrn2606 · Cited by 1,120
Self-citationSex differences in pain and pain inhibition: multiple explanations of a controversial phenomenon
Mogil, J. S. (2012) · Nature Reviews Neuroscience · doi:10.1038/nrn3360 · Cited by 1,065
Self-citationQualitative sex differences in pain processing: emerging evidence of a biased literature
Mogil, J. S. (2020) · Nature Reviews Neuroscience · doi:10.1038/s41583-020-0310-6 · Cited by 691
Self-citationResearch progress in calcitonin gene-related peptide and bone repair
Wang, Q., Qin, H., Deng, J., Xu, H., Liu, S., Weng, J., & Zeng, H. (2023) · Biomolecules · doi:10.3390/biom13050838 · Cited by 58
Metadata
- Authors
- Mogil, J. S., Miermeister, F., Seifert, F., Strasburg, K., Zimmermann, K., Reinold, H., Austin, J.-S., Bernardini, N., Chesler, E. J., Hofmann, H. A., Hordo, C., Messlinger, K., Nemmani, K. V. S., Rankin, A. L., Ritchie, J., Siegling, A., Smith, S. B., Sotocinal, S., Vater, A., Lehto, S. G., Klussmann, S., Quirion, R., Michaelis, M., Devor, M., & Reeh, P. W.
- Venue
- Proceedings of the National Academy of Sciences
- Published
- 2005-08-23
- Volume
- 102
- Issue
- 36
- Pages
- 12938-12943
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- OpenAlex
- W2096847273
- Cited by
- 160
- References
- 0
- FWCI
- 8.03
- Type
- journal article
- Language
- en
- Open access
- green
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- Mogil, J. S., Miermeister, F., Seifert, F., Strasburg, K., Zimmermann, K., Reinold, H., Austin, J.-S., Bernardini, N., Chesler, E. J., Hofmann, H. A., Hordo, C., Messlinger, K., Nemmani, K. V. S., Rankin, A. L., Ritchie, J., Siegling, A., Smith, S. B., Sotocinal, S., Vater, A., . . . Reeh, P. W. (2005). Variable sensitivity to noxious heat is mediated by differential expression of the CGRP gene. Proceedings of the National Academy of Sciences. https://doi.org/10.1073/pnas.0503264102
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
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