title: Distinct subsets of unmyelinated primary sensory fibers mediate behavioral responses to noxious thermal and mechanical stimuli.
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.
authors.affiliation: Department of Anatomy, University of California, San Francisco CA 94158, USA.
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Cavanaugh
authors.forename: Hyosang
authors.initials: H
authors.lastname: Lee
authors.forename: Liching
authors.initials: L
authors.lastname: Lo
authors.forename: Shannon D
authors.initials: SD
authors.lastname: Shields
authors.forename: Mark J
authors.initials: MJ
authors.lastname: Zylka
authors.forename: Allan I
authors.initials: AI
authors.lastname: Basbaum
authors.forename: David J
authors.initials: DJ
authors.lastname: Anderson
mesh_terms: D000818:Animals; D001522:Behavior, Animal; D001921:Brain / Q000502:physiology*; D003080:Cold Temperature; D004167:Diphtheria Toxin / Q000494:pharmacology; D006358:Hot Temperature; D051379:Mice; D008817:Mice, Mutant Strains; D036421:Nerve Fibers, Unmyelinated / Q000502:physiology*; D010146:Pain / Q000503:physiopathology*; D043562:Receptors, G-Protein-Coupled / Q000235:genetics; D013314:Stress, Mechanical; D050916:TRPV Cation Channels / Q000037:antagonists & inhibitors
chemical_list: D004167:Diphtheria Toxin; C497098:Mrgprd protein, mouse; D043562:Receptors, G-Protein-Coupled; D050916:TRPV Cation Channels; C493921:TRPV1 protein, mouse