Journal
NATURE COMMUNICATIONS
Volume 5, Issue -, Pages -Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/ncomms5122
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Funding
- NIH [P01 NS47399, R01DE022750, R01GM087369]
- Blaustein Pain Research and Education Fund
- Brain Science Institute
- Neurosurgery Pain Research Institute at the Johns Hopkins University
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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 beta-alanine, an MrgprD agonist, excite vigorously all QCs. Only 40% of SCs respond to beta-alanine, and their response is only half that of QCs. Mechanically insensitive C-fibres (C-MIAs) are beta-alanine insensitive but vigorously respond to capsaicin and histamine with distinct discharge patterns. Calcium imaging reveals that b-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 beta-alanine responsive QC fibres likely corresponding to murine MrgprD-expressing, non-peptidergic nociceptive afferents.
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