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© 2019, Smith et al. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.

Abstract

Nociceptive information is relayed through the spinal cord dorsal horn, a critical area in sensory processing. The neuronal circuits in this region that underpin sensory perception must be clarified to better understand how dysfunction can lead to pathological pain. This study used an optogenetic approach to selectively activate spinal interneurons that express the calcium-binding protein calretinin (CR). We show that these interneurons form an interconnected network that can initiate and sustain enhanced excitatory signaling, and directly relay signals to lamina I projection neurons. Photoactivation of CR interneurons in vivo resulted in a significant nocifensive behavior that was morphine sensitive, caused a conditioned place aversion, and was enhanced by spared nerve injury. Furthermore, halorhodopsin-mediated inhibition of these interneurons elevated sensory thresholds. Our results suggest that dorsal horn circuits that involve excitatory CR neurons are important for the generation and amplification of pain and identify these interneurons as a future analgesic target.

Details

Title
Calretinin positive neurons form an excitatory amplifier network in the spinal cord dorsal horn
Author
Smith, Kelly M; Browne, Tyler J; Davis, Olivia C; Coyle, A; Boyle, Kieran A; Watanabe, Masahiko; Dickinson, Sally A; Iredale, Jacqueline A; Gradwell, Mark A; Jobling, Phillip; Callister, Robert J; Dayas, Christopher V; Hughes, David I; Graham, Brett A
University/institution
U.S. National Institutes of Health/National Library of Medicine
Publication year
2019
Publication date
2019
Publisher
eLife Sciences Publications Ltd.
e-ISSN
2050084X
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
2331591412
Copyright
© 2019, Smith et al. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.