title: Targeted ablation, silencing, and activation establish glycinergic dorsal horn neurons as key components of a spinal gate for pain and itch.
abstract: The gate control theory of pain proposes that inhibitory neurons of the spinal dorsal horn exert critical control over the relay of nociceptive signals to higher brain areas. Here we investigated how the glycinergic subpopulation of these neurons contributes to modality-specific pain and itch processing. We generated a GlyT2::Cre transgenic mouse line suitable for virus-mediated retrograde tracing studies and for spatially precise ablation, silencing, and activation of glycinergic neurons. We found that these neurons receive sensory input mainly from myelinated primary sensory neurons and that their local toxin-mediated ablation or silencing induces localized mechanical, heat, and cold hyperalgesia; spontaneous flinching behavior; and excessive licking and biting directed toward the corresponding skin territory. Conversely, local pharmacogenetic activation of the same neurons alleviated neuropathic hyperalgesia and chloroquine- and histamine-induced itch. These results establish glycinergic neurons of the spinal dorsal horn as key elements of an inhibitory pain and itch control circuit.
authors: Institute of Pharmacology and Toxicology, University of Zurich, Winterthurerstrasse 190, 8057 Zürich, Switzerland.
authors: Edmund
authors: E
authors: Foster
authors: Institute of Pharmacology and Toxicology, University of Zurich, Winterthurerstrasse 190, 8057 Zürich, Switzerland.
authors: Hendrik
authors: H
authors: Wildner
authors: Institute of Pharmacology and Toxicology, University of Zurich, Winterthurerstrasse 190, 8057 Zürich, Switzerland; Institute of Pharmaceutical Sciences, Swiss Federal Institute of Technology (ETH) Zürich, Vladimir Prelog Weg 4, 8093 Zürich, Switzerland.
authors: Laetitia
authors: L
authors: Tudeau
authors: Institute of Pharmacology and Toxicology, University of Zurich, Winterthurerstrasse 190, 8057 Zürich, Switzerland; Institute of Pharmaceutical Sciences, Swiss Federal Institute of Technology (ETH) Zürich, Vladimir Prelog Weg 4, 8093 Zürich, Switzerland.
authors: Sabine
authors: S
authors: Haueter
authors: Institute of Pharmacology and Toxicology, University of Zurich, Winterthurerstrasse 190, 8057 Zürich, Switzerland.
authors: William T
authors: WT
authors: Ralvenius
authors: Institute of Pharmacology and Toxicology, University of Zurich, Winterthurerstrasse 190, 8057 Zürich, Switzerland; Institute of Pharmaceutical Sciences, Swiss Federal Institute of Technology (ETH) Zürich, Vladimir Prelog Weg 4, 8093 Zürich, Switzerland.
authors: Monika
authors: M
authors: Jegen
authors: Institute of Pharmacology and Toxicology, University of Zurich, Winterthurerstrasse 190, 8057 Zürich, Switzerland.
authors: Helge
authors: H
authors: Johannssen
authors: Institute of Pharmacology and Toxicology, University of Zurich, Winterthurerstrasse 190, 8057 Zürich, Switzerland.
authors: Ladina
authors: L
authors: Hösli
authors: Institute of Pharmacology and Toxicology, University of Zurich, Winterthurerstrasse 190, 8057 Zürich, Switzerland; Institute of Pharmaceutical Sciences, Swiss Federal Institute of Technology (ETH) Zürich, Vladimir Prelog Weg 4, 8093 Zürich, Switzerland.
authors: Karen
authors: K
authors: Haenraets
authors: Gene Center, Ludwig Maximilians University Munich, Max von Pettenkofer Institute of Virology, Feodor Lynen Strasse 25, 81377 Munich, Germany.
authors: Alexander
authors: A
authors: Ghanem
authors: Gene Center, Ludwig Maximilians University Munich, Max von Pettenkofer Institute of Virology, Feodor Lynen Strasse 25, 81377 Munich, Germany.
authors: Karl-Klaus
authors: KK
authors: Conzelmann
authors: Experimental Biomedicine, University of Würzburg, Josef Schneider Strasse 2, 97080 Würzburg, Germany.
authors: Michael
authors: M
authors: Bösl
authors: Institute of Pharmacology and Toxicology, University of Zurich, Winterthurerstrasse 190, 8057 Zürich, Switzerland; Institute of Pharmaceutical Sciences, Swiss Federal Institute of Technology (ETH) Zürich, Vladimir Prelog Weg 4, 8093 Zürich, Switzerland. Electronic address: zeilhofer@pharma.uzh.ch.
authors: Hanns Ulrich
authors: HU
authors: Zeilhofer
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D005998:Glycine / Q000378:metabolism; D006930:Hyperalgesia / Q000473:pathology; D051379:Mice; D008822:Mice, Transgenic; D009415:Nerve Net / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D009474:Neurons / Q000166:cytology*; D010146:Pain / Q000503:physiopathology*; D010523:Peripheral Nervous System Diseases / Q000235:genetics / Q000473:pathology / Q000503:physiopathology; D020671:Posterior Horn Cells / Q000502:physiology; D011537:Pruritus / Q000503:physiopathology*; D066148:Spinal Cord Dorsal Horn / Q000166:cytology*
chemical_list: D005998:Glycine