Department of Neurosurgery, Neurosurgery Pain Research Institute, School of Medicine, Johns Hopkins University, Baltimore, United States; Department of Pharmacy Practice and Pharmaceutical Sciences, University of Minnesota, Duluth, United States
Molecular Genetics Section, National Institute of Dental and Craniofacial Research, Bethesda, United States; Department of Experimental Pain Research, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany
Department of Anesthesiology, School of Medicine, Yale University, New Haven, United States; Department of Anesthesiology, Intensive Care Medicine and Pain Management, Medical Faculty of Ruhr-University Bochum, BG University Hospital Bergmannsheil, Bochum, Germany
The Solomon H. Snyder Department of Neuroscience, School of Medicine, Johns Hopkins University, Baltimore, United States; Howard Hughes Medical Institute, Johns Hopkins University School of Medicine, Baltimore, United States
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.
