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

Daniel J. Cavanaugh, Hyosang Lee, Liching Lo, Shannon D. Shields, Mark J. Zylka, Allan I. Basbaum, David J. Anderson

Research output: Contribution to journalArticlepeer-review

559 Scopus citations

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.

Original languageEnglish
Pages (from-to)9075-9080
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume106
Issue number22
DOIs
StatePublished - 2 Jun 2009

Keywords

  • Mrgprd
  • Nociception
  • TRPV1

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