Targeted ablation, silencing, and activation establish glycinergic dorsal horn neurons as key components of a spinal gate for pain and itch.

Neuron 2015 Mar 18

filter terms:

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.

Citation

Edmund Foster, Hendrik Wildner, Laetitia Tudeau, Sabine Haueter, William T Ralvenius, Monika Jegen, Helge Johannssen, Ladina Hösli, Karen Haenraets, Alexander Ghanem, Karl-Klaus Conzelmann, Michael Bösl, Hanns Ulrich Zeilhofer. Targeted ablation, silencing, and activation establish glycinergic dorsal horn neurons as key components of a spinal gate for pain and itch. Neuron. 2015 Mar 18;85(6):1289-304