Cell Reports
Volume 17, Issue 11, 13 December 2016, Pages 3049-3061
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Article
Reversible Induction of Pain Hypersensitivity following Optogenetic Stimulation of Spinal Astrocytes

https://doi.org/10.1016/j.celrep.2016.11.043Get rights and content
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Highlights

  • Optogenetics applied to spinal astrocytes in live animals

  • Optogenetic stimulation of spinal astrocytes induces pain hypersensitivity

  • Spinal astrocytic activation necessary/sufficient for optogenetic pain induction

  • Suggests possible basis for therapeutic strategy for chronic pain

Summary

While glial activation is an integral part of pain pathogenesis, the existence of a causal relationship between glia and pain processing has yet to be demonstrated in vivo. Here, we have investigated whether the activation of spinal astrocytes could directly evoke pain hypersensitivity in vivo via the use of optogenetic techniques. Optogenetic stimulation of channelrhopdopsin-2 (ChR)-expressing spinal astrocytes induced pain hypersensitivity in a reversible and time-dependent manner, which was accompanied by glial activation, NR1 phosphorylation, ATP release, and the production of proalgesic mediators. Photostimulation of ChR2-expressing astrocytes in culture and spinal slices recapitulated in vivo findings, demonstrating the release of proalgesic mediators and electrophysiological disinhibition of spinal projection neurons. These findings deepen our understanding of the role of astrocytes in pain pathogenesis and provide the scientific basis for an astrocyte-oriented pain treatment.

Keywords

pain
astrocytes
neuroinflammation
optogenetics
spinal cord
central sensitization

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