Optogenetic Activation of Non-Nociceptive Aβ Fibers Induces Neuropathic Pain-Like Sensory and Emotional Behaviors after Nerve Injury in Rats

ENeuro
Ryoichi TashimaMakoto Tsuda

Abstract

Neuropathic pain is caused by peripheral nerve injury (PNI). One hallmark symptom is allodynia (pain caused by normally innocuous stimuli), but its mechanistic underpinning remains elusive. Notably, whether selective stimulation of non-nociceptive primary afferent Aβ fibers indeed evokes neuropathic pain-like sensory and emotional behaviors after PNI is unknown, because of the lack of tools to manipulate Aβ fiber function in awake, freely moving animals. In this study, we used a transgenic rat line that enables stimulation of non-nociceptive Aβ fibers by a light-activated channel (channelrhodopsin-2; ChR2). We found that illuminating light to the plantar skin of these rats with PNI elicited pain-like withdrawal behaviors that were resistant to morphine. Light illumination to the skin of PNI rats increased the number of spinal dorsal horn (SDH) Lamina I neurons positive to activity markers (c-Fos and phosphorylated extracellular signal-regulated protein kinase; pERK). Whole-cell recording revealed that optogenetic Aβ fiber stimulation after PNI caused excitation of Lamina I neurons, which were normally silent by this stimulation. Moreover, illuminating the hindpaw of PNI rats resulted in activation of central amygdaloid neurons ...Continue Reading

Citations

Sep 12, 2019·International Journal of Molecular Sciences·Yuhua YinDong Woon Kim
Nov 30, 2018·Open Biology·Kazuhide Inoue
Mar 4, 2020·Neuromodulation : Journal of the International Neuromodulation Society·Takeshi Uno
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Jun 26, 2020·Physiological Reviews·Nanna Brix FinnerupTroels Staehelin Jensen
Jan 13, 2021·Proceedings of the National Academy of Sciences of the United States of America·Ryoichi TashimaMakoto Tsuda
Oct 24, 2020·Frontiers in Cellular Neuroscience·Peter A Smith
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Methods Mentioned

BETA
transgenic

Software Mentioned

pCLAMP
GraphPad Prism
Clampfit
ImageJ

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