Three functionally distinct classes of C-fibre nociceptors in primates

Nat Commun. 2014 Jun 20:5:4122. doi: 10.1038/ncomms5122.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Action Potentials / physiology*
  • Animals
  • Capsaicin / pharmacology
  • Ganglia, Spinal / cytology*
  • Ganglia, Spinal / drug effects
  • Histamine / pharmacology
  • Hot Temperature*
  • Injections, Intradermal
  • Macaca
  • Male
  • Nerve Fibers, Unmyelinated / physiology*
  • Nociceptors / classification*
  • Nociceptors / drug effects
  • Nociceptors / physiology*
  • Physical Stimulation
  • Statistics, Nonparametric
  • Stimulation, Chemical
  • beta-Alanine / administration & dosage
  • beta-Alanine / pharmacology

Substances

  • beta-Alanine
  • Histamine
  • Capsaicin