Mechanisms of itch evoked by β-alanine.
β-Alanine, a popular supplement for muscle building, induces itch and tingling after consumption, but the underlying molecular and neural mechanisms are obscure. Here we show that, in mice, β-alanine elicited itch-associated behavior that requires MrgprD, a G-protein-coupled receptor expressed by a subpopulation of primary sensory neurons. These neurons exclusively innervate the skin, respond to β-alanine, heat, and mechanical noxious stimuli but do not respond to histamine. In humans, intradermally injected β-alanine induced itch but neither wheal nor flare, suggesting that the itch was not mediated by histamine. Thus, the primary sensory neurons responsive to β-alanine are likely part of a histamine-independent itch neural circuit and a target for treating clinical itch that is unrelieved by anti-histamines.
The Solomon H. Snyder Department of Neuroscience, Center for Sensory Biology, and Howard Hughes Medical Institute, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.
Qin
Q
Liu
Parul
P
Sikand
Chao
C
Ma
Zongxiang
Z
Tang
Liang
L
Han
Zhe
Z
Li
Shuohao
S
Sun
Robert H
RH
LaMotte
Xinzhong
X
Dong
D000328:Adult; D000818:Animals; D005260:Female; D005727:Ganglia, Spinal / Q000378:metabolism / Q000502:physiology; D055879:Gene Knock-In Techniques; D006801:Humans; D007271:Injections, Intradermal / Q000379:methods; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008875:Middle Aged; D011537:Pruritus / Q000209:etiology* / Q000235:genetics / Q000378:metabolism*; D043562:Receptors, G-Protein-Coupled / Q000096:biosynthesis* / Q000172:deficiency / Q000502:physiology; D011984:Sensory Receptor Cells / Q000378:metabolism / Q000473:pathology; D055815:Young Adult; D015091:beta-Alanine / Q000633:toxicity*
C497098:Mrgprd protein, mouse; D043562:Receptors, G-Protein-Coupled; D015091:beta-Alanine