title: Three functionally distinct classes of C-fibre nociceptors in primates.
abstract: In primates, C-fibre polymodal nociceptors are broadly classified into two groups based on mechanosensitivity. Here we demonstrate that mechanically sensitive polymodal nociceptors that respond either quickly (QC) or slowly (SC) to a heat stimulus differ in responses to a mild burn, heat sensitization, conductive properties and chemosensitivity. Superficially applied capsaicin and intradermal injection of β-alanine, an MrgprD agonist, excite vigorously all QCs. Only 40% of SCs respond to β-alanine, and their response is only half that of QCs. Mechanically insensitive C-fibres (C-MIAs) are β-alanine insensitive but vigorously respond to capsaicin and histamine with distinct discharge patterns. Calcium imaging reveals that β-alanine and histamine activate distinct populations of capsaicin-responsive neurons in primate dorsal root ganglion. We suggest that histamine itch and capsaicin pain are peripherally encoded in C-MIAs, and that primate polymodal nociceptive afferents form three functionally distinct subpopulations with β-alanine responsive QC fibres likely corresponding to murine MrgprD-expressing, non-peptidergic nociceptive afferents.
authors.affiliation: Department of Neurosurgery, School of Medicine, Johns Hopkins University, Baltimore, Maryland 21287, USA.
authors.forename: Matthew
authors.initials: M
authors.lastname: Wooten
authors.affiliation: Department of Neuroscience, School of Medicine, Johns Hopkins University, Baltimore, Maryland 21205, USA.
authors.forename: Hao-Jui
authors.initials: HJ
authors.lastname: Weng
authors.affiliation: Department of Neurosurgery, School of Medicine, Johns Hopkins University, Baltimore, Maryland 21287, USA.
authors.forename: Timothy V
authors.initials: TV
authors.lastname: Hartke
authors.affiliation: Department of Anesthesiology and Critical Care Medicine, School of Medicine, Johns Hopkins University, Baltimore, Maryland 21287, USA.
authors.forename: Jasenka
authors.initials: J
authors.lastname: Borzan
authors.affiliation: Department of Neurosurgery, School of Medicine, Johns Hopkins University, Baltimore, Maryland 21287, USA.
authors.forename: Amanda H
authors.initials: AH
authors.lastname: Klein
authors.affiliation: Department of Mathematics and Computer Science, Bethel University, St Paul, Minnesota 55112, USA.
authors.forename: Brian
authors.initials: B
authors.lastname: Turnquist
authors.affiliation: Department of Neuroscience, School of Medicine, Johns Hopkins University, Baltimore, Maryland 21205, USA.
authors.forename: Xinzhong
authors.initials: X
authors.lastname: Dong
authors.affiliation: Department of Neurosurgery, School of Medicine, Johns Hopkins University, Baltimore, Maryland 21287, USA.
authors.forename: Richard A
authors.initials: RA
authors.lastname: Meyer
authors.affiliation: Department of Neurosurgery, School of Medicine, Johns Hopkins University, Baltimore, Maryland 21287, USA.
authors.forename: Matthias
authors.initials: M
authors.lastname: Ringkamp
mesh_terms: D000200:Action Potentials / Q000502:physiology*; D000818:Animals; D002211:Capsaicin / Q000494:pharmacology; D005727:Ganglia, Spinal / Q000166:cytology* / Q000187:drug effects; D006632:Histamine / Q000494:pharmacology; D006358:Hot Temperature; D007271:Injections, Intradermal; D008251:Macaca; D008297:Male; D036421:Nerve Fibers, Unmyelinated / Q000502:physiology*; D009619:Nociceptors / Q000145:classification* / Q000187:drug effects / Q000502:physiology*; D010812:Physical Stimulation; D018709:Statistics, Nonparametric; D013268:Stimulation, Chemical; D015091:beta-Alanine / Q000008:administration & dosage / Q000494:pharmacology
chemical_list: D015091:beta-Alanine; D006632:Histamine; D002211:Capsaicin