1. Targeted ablation, silencing, and activation establish glycinergic dorsal horn neurons as key components of a spinal gate for pain and itch.
- Author
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Foster E, Wildner H, Tudeau L, Haueter S, Ralvenius WT, Jegen M, Johannssen H, Hösli L, Haenraets K, Ghanem A, Conzelmann KK, Bösl M, and Zeilhofer HU
- Subjects
- Animals, Disease Models, Animal, Glycine metabolism, Hyperalgesia pathology, Mice, Mice, Transgenic, Nerve Net metabolism, Nerve Net pathology, Peripheral Nervous System Diseases genetics, Peripheral Nervous System Diseases pathology, Peripheral Nervous System Diseases physiopathology, Posterior Horn Cells physiology, Nerve Net physiopathology, Neurons cytology, Pain physiopathology, Pruritus physiopathology, Spinal Cord Dorsal Horn cytology
- 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., (Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.)
- Published
- 2015
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