In humans, intradermal administration of β-alanine (ALA) and bovine adrenal medulla peptide 8-22 (BAM8-22) evokes the sensation of itch. Currently, it is unknown which human dorsal root ganglion (DRG) neurons express the receptors of these pruritogens, MRGPRD and MRGPRX1, respectively, and which cutaneous afferents these pruritogens activate in primate. In situ hybridization studies revealed that MRGPRD and MRGPRX1 are co-expressed in a subpopulation of TRPV1+ human DRG neurons. In electrophysiological recordings in nonhuman primates ( Macaca nemestrina), subtypes of polymodal C-fiber nociceptors are preferentially activated by ALA and BAM8-22, with significant overlap. When pruritogens ALA, BAM8-22, and histamine, which activate different subclasses of C-fiber afferents, are administered in combination, human volunteers report itch and nociceptive sensations similar to those induced by a single pruritogen. Our results provide evidence for differences in pruriceptive processing between primates and rodents, and do not support the spatial contrast theory of coding of itch and pain.
Bibliographical noteFunding Information:
National Institute of Arthritis and Musculoskeletal and Skin DiseasesR01070875 Robert H LaMotte Matthias Ringkamp. National Institute on Drug AbuseK01 DA042902 Amanda Klein. Deutsche Forschungsgemeinschaft FOR 2690 Hans J?rgen Solinski. Deutsche Forschungsgemeinschaft Fellowship grant 326726541 Nathalie Malewicz. National Institute of Dental and Craniofacial Research ZIADE000721-18 Mark A Hoon. National Institute of Neurological Disorders and Stroke T32NS070201 Elizabeth I Sypek
This study was supported by NIH grants R01 AR070875 (MR, RHL) and K01 DA042902 (AHK) and 2T32NS070201 (EIS) and U42OD013117 (Johns Hopkins, NIH-supported pigtailed macaque breeding colony); by the German Research Foundation (DFG): project grant FOR 2690 (HJS) and Research Fellowship grant 326726541 (NMM), the intramural research program of the National Institute of Dental and Craniofacial Research, National Institutes of Health, project ZIADE000721-18 (MAH), and the Neurosurgery Pain Research Institute at the Johns Hopkins University. Human tissue was obtained from the NIH NeuroBioBank at the University of Maryland, Baltimore, MD.
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