• Matthew Wooten, Hao-Jui Weng, Timothy V Hartke, Jasenka Borzan, Amanda H Klein, Brian Turnquist, Xinzhong Dong, Richard A Meyer, and Matthias Ringkamp.
• Department of Neurosurgery, School of Medicine, Johns Hopkins University, Baltimore, Maryland 21287, USA.
• Nat Commun. 2014 Jun 20; 5: 4122.

AbstractIn 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.

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