A subpopulation of nociceptors specifically linked to itch
Top Cited Papers
Open Access
- 23 December 2012
- journal article
- research article
- Published by Springer Science and Business Media LLC in Nature Neuroscience
- Vol. 16 (2), 174-182
- https://doi.org/10.1038/nn.3289
Abstract
Dorsal root ganglion neurons respond to both painful and itchy stimuli, but whether itch-specific neurons exist was, up until now, unknown. Here the authors describe a group of MrgprA3-expressing neurons that innervate the superficial layers of the skin and selectively sense itch. 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.Keywords
This publication has 51 references indexed in Scilit:
- Sensory responses to injection and punctate application of capsaicin and histamine to the skinPain, 2011
- VGLUT2-Dependent Glutamate Release from Nociceptors Is Required to Sense Pain and Suppress ItchNeuron, 2010
- VGLUT2-Dependent Sensory Neurons in the TRPV1 Population Regulate Pain and ItchNeuron, 2010
- In vivo visualization and functional characterization of primary somatic neuronsJournal of Neuroscience Methods, 2010
- Loss of Inhibitory Interneurons in the Dorsal Spinal Cord and Elevated Itch in Bhlhb5 Mutant MiceNeuron, 2010
- Sensory Neuron-Specific GPCR Mrgprs Are Itch Receptors Mediating Chloroquine-Induced PruritusCell, 2009
- Cellular and Molecular Mechanisms of PainCell, 2009
- Similar itch and nociceptive sensations evoked by punctate cutaneous application of capsaicin, histamine and cowhagePain, 2009
- Behavioral differentiation between itch and pain in mousePain, 2008
- Topographically Distinct Epidermal Nociceptive Circuits Revealed by Axonal Tracers Targeted to MrgprdNeuron, 2005