title: A subpopulation of nociceptors specifically linked to itch.
abstract: Itch-specific neurons have been sought for decades. The existence of such neurons has been doubted recently as a result of the observation that itch-mediating neurons also respond to painful stimuli. We genetically labeled and manipulated MrgprA3(+) neurons in the dorsal root ganglion (DRG) and found that they exclusively innervated the epidermis of the skin and responded to multiple pruritogens. Ablation of MrgprA3(+) neurons led to substantial reductions in scratching evoked by multiple pruritogens and occurring spontaneously under chronic itch conditions, whereas pain sensitivity remained intact. Notably, mice in which TRPV1 was exclusively expressed in MrgprA3(+) neurons exhibited itch, but not pain, behavior in response to capsaicin. Although MrgprA3(+) neurons were sensitive to noxious heat, activation of TRPV1 in these neurons by noxious heat did not alter pain behavior. These data suggest that MrgprA3 defines a specific subpopulation of DRG neurons mediating itch. Our study opens new avenues for studying itch and developing anti-pruritic therapies.
authors.affiliation: The Solomon H. Snyder Department of Neuroscience, Center for Sensory Biology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
authors.forename: Liang
authors.initials: L
authors.lastname: Han
authors.forename: Chao
authors.initials: C
authors.lastname: Ma
authors.forename: Qin
authors.initials: Q
authors.lastname: Liu
authors.forename: Hao-Jui
authors.initials: HJ
authors.lastname: Weng
authors.forename: Yiyuan
authors.initials: Y
authors.lastname: Cui
authors.forename: Zongxiang
authors.initials: Z
authors.lastname: Tang
authors.forename: Yushin
authors.initials: Y
authors.lastname: Kim
authors.forename: Hong
authors.initials: H
authors.lastname: Nie
authors.forename: Lintao
authors.initials: L
authors.lastname: Qu
authors.forename: Kush N
authors.initials: KN
authors.lastname: Patel
authors.forename: Zhe
authors.initials: Z
authors.lastname: Li
authors.forename: Benjamin
authors.initials: B
authors.lastname: McNeil
authors.forename: Shaoqiu
authors.initials: S
authors.lastname: He
authors.forename: Yun
authors.initials: Y
authors.lastname: Guan
authors.forename: Bo
authors.initials: B
authors.lastname: Xiao
authors.forename: Robert H
authors.initials: RH
authors.lastname: Lamotte
authors.forename: Xinzhong
authors.initials: X
authors.lastname: Dong
mesh_terms: D000200:Action Potentials / Q000187:drug effects / Q000235:genetics; D000818:Animals; D018501:Antirheumatic Agents / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D002211:Capsaicin / Q000494:pharmacology; D002478:Cells, Cultured; D002738:Chloroquine / Q000494:pharmacology; D004817:Epidermis / Q000294:innervation; D005727:Ganglia, Spinal / Q000166:cytology; D005786:Gene Expression Regulation / Q000502:physiology; D049452:Green Fluorescent Proteins / Q000235:genetics; D006632:Histamine / Q000009:adverse effects; D006358:Hot Temperature / Q000009:adverse effects; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009043:Motor Activity / Q000187:drug effects; D009412:Nerve Fibers / Q000502:physiology; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009619:Nociceptors / Q000145:classification* / Q000502:physiology*; D010147:Pain Measurement; D017288:Pain Threshold / Q000502:physiology; D018408:Patch-Clamp Techniques; D010446:Peptide Fragments / Q000009:adverse effects; D037121:Plant Lectins / Q000378:metabolism; D011506:Proteins / Q000235:genetics; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D011537:Pruritus / Q000139:chemically induced / Q000235:genetics / Q000473:pathology*; D022661:RNA, Untranslated; D018004:Receptors, Bombesin / Q000378:metabolism; D043562:Receptors, G-Protein-Coupled / Q000235:genetics; D045442:Rotarod Performance Test; D011984:Sensory Receptor Cells / Q000187:drug effects / Q000502:physiology*; D018689:Sensory System Agents / Q000494:pharmacology; D013116:Spinal Cord / Q000166:cytology; D050916:TRPV Cation Channels / Q000172:deficiency / Q000378:metabolism
chemical_list: D018501:Antirheumatic Agents; C110853:Gt(ROSA)26Sor non-coding RNA, mouse; C546475:MrgprA3 protein, mouse; D009419:Nerve Tissue Proteins; D010446:Peptide Fragments; D037121:Plant Lectins; D011506:Proteins; D016760:Proto-Oncogene Proteins c-fos; D022661:RNA, Untranslated; D018004:Receptors, Bombesin; D043562:Receptors, G-Protein-Coupled; D018689:Sensory System Agents; D050916:TRPV Cation Channels; C493921:TRPV1 protein, mouse; C571042:bovine adrenal medulla 8-22; C034981:tomato lectin; D049452:Green Fluorescent Proteins; D006632:Histamine; D002738:Chloroquine; D002211:Capsaicin; D002118:Calcium