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Distinct subsets of unmyelinated primary sensory fibers mediate behavioral responses to noxious thermal and mechanical stimuli

Cavanaugh, Daniel J. and Lee, Hyosang and Lo, Liching and Shields, Shannon D. and Zylka, Mark J. and Basbaum, Allan I. and Anderson, David J. (2009) Distinct subsets of unmyelinated primary sensory fibers mediate behavioral responses to noxious thermal and mechanical stimuli. Proceedings of the National Academy of Sciences of the United States of America, 106 (22). pp. 9075-9080. ISSN 0027-8424. http://resolver.caltech.edu/CaltechAUTHORS:20090814-100042259

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Abstract

Behavioral responses to painful stimuli require peripheral sensory neurons called nociceptors. Electrophysiological studies show that most C-fiber nociceptors are polymodal (i.e., respond to multiple noxious stimulus modalities, such as mechanical and thermal); nevertheless, these stimuli are perceived as distinct. Therefore, it is believed that discrimination among these modalities only occurs at spinal or supraspinal levels of processing. Here, we provide evidence to the contrary. Genetic ablation in adulthood of unmyelinated sensory neurons expressing the G protein-coupled receptor Mrgprd reduces behavioral sensitivity to noxious mechanical stimuli but not to heat or cold stimuli. Conversely, pharmacological ablation of the central branches of TRPV1+ nociceptors, which constitute a nonoverlapping population, selectively abolishes noxious heat pain sensitivity. Combined elimination of both populations yielded an additive phenotype with no additional behavioral deficits, ruling out a redundant contribution of these populations to heat and mechanical pain sensitivity. This double-dissociation suggests that the brain can distinguish different noxious stimulus modalities from the earliest stages of sensory processing.


Item Type:Article
Related URLs:
URLURL TypeDescription
http://dx.doi.org/10.1073/pnas.0901507106DOIUNSPECIFIED
http://www.pnas.org/content/106/22/9075.full.pdf+htmlPublisherUNSPECIFIED
Additional Information:© 2009 National Academy of Sciences. Freely available online through the PNAS open access option. Contributed by David J. Anderson, February 12, 2009 (sent for review December 22, 2008). Published online before print May 18, 2009, doi: 10.1073/pnas.0901507106 This work was supported, in part, by National Institutes of Health Grants PO1NS048499 (to D.J.A. and A.I.B.) and NS14627 (to A.I.B.); by awards from the National Alliance for Research on Schizophrenia and Depression, the Searle Scholars Program, and the Whitehall, Klingenstein, Sloan, and Rita Allen Foundations (to M.J.Z.); and by an award from the Christopher and Dana Reeve Foundation to (H.L.). We thank Kenji Kohno for the DTR (TRECK-1) cDNA clone, Joao Braz for help with retrograde tracing, Noritaka Imamachi for help with intrathecal injections, and Shirley Pease and staff for assistance with genetically modified mice. D.J.A. is an Investigator of the Howard Hughes Medical Institute. Author contributions: D.J.C., H.L., S.D.S., M.J.Z., A.I.B., and D.J.A. designed research; D.J.C., H.L., L.L., S.D.S., and M.J.Z. performed research; D.J.C., H.L., L.L., S.D.S., M.J.Z., A.I.B., and D.J.A. analyzed data; and D.J.C., A.I.B., and D.J.A. wrote the paper. The authors declare no conflict of interest. This article contains supporting information online at www.pnas.org/cgi/content/full/0901507106/DCSupplemental.
Funders:
Funding AgencyGrant Number
NIHPO1NS048499
NIHNS14627
National Alliance for Research on Schizophrenia and DepressionUNSPECIFIED
Searle Scholars ProgramUNSPECIFIED
Howard Hughes Medical InstituteUNSPECIFIED
Record Number:CaltechAUTHORS:20090814-100042259
Persistent URL:http://resolver.caltech.edu/CaltechAUTHORS:20090814-100042259
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:15026
Collection:CaltechAUTHORS
Deposited By: Ruth Sustaita
Deposited On:14 Aug 2009 17:55
Last Modified:14 Nov 2014 19:20

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