Optogenetic activation of non-nociceptive aβ fibers induces neuropathic pain-like sensory and emotional behaviors after nerve injury in rats

Ryoichi Tashima, Keisuke Koga, Misuzu Sekine, Kensho Kanehisa, Yuta Koro, Keiko Tominaga, Katsuyuki Matsushita, Hidetoshi Saitoh, Yugo Fukazawa, Kazuhide Inoue, Hiromu Yawo, Hidemasa Furue, Tsuda Makoto

研究成果: ジャーナルへの寄稿記事

8 引用 (Scopus)

抄録

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 and produced an aversion to illumination. Thus, these findings provide the first evidence that optogenetic activation of primary afferent Aβ fibers in PNI rats produces excitation of Lamina I neurons and neuropathic pain-like behaviors that were resistant to morphine treatment. This approach may provide a new path for investigating circuits and behaviors of Aβ fiber-mediated neuropathic allodynia with sensory and emotional aspects after PNI and for discovering novel drugs to treat neuropathic pain.

元の言語英語
記事番号e0450-17.2018
ジャーナルeNeuro
5
発行部数1
DOI
出版物ステータス出版済み - 1 1 2018

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Optogenetics
Peripheral Nerve Injuries
Neuralgia
Myelinated Nerve Fibers
Wounds and Injuries
Neurons
Hyperalgesia
Lighting
Light
Morphine
Transgenic Rats
Pain
Skin
Extracellular Signal-Regulated MAP Kinases
Patch-Clamp Techniques
Protein Kinases

All Science Journal Classification (ASJC) codes

  • Neuroscience(all)

これを引用

Optogenetic activation of non-nociceptive aβ fibers induces neuropathic pain-like sensory and emotional behaviors after nerve injury in rats. / Tashima, Ryoichi; Koga, Keisuke; Sekine, Misuzu; Kanehisa, Kensho; Koro, Yuta; Tominaga, Keiko; Matsushita, Katsuyuki; Saitoh, Hidetoshi; Fukazawa, Yugo; Inoue, Kazuhide; Yawo, Hiromu; Furue, Hidemasa; Makoto, Tsuda.

:: eNeuro, 巻 5, 番号 1, e0450-17.2018, 01.01.2018.

研究成果: ジャーナルへの寄稿記事

Tashima, Ryoichi ; Koga, Keisuke ; Sekine, Misuzu ; Kanehisa, Kensho ; Koro, Yuta ; Tominaga, Keiko ; Matsushita, Katsuyuki ; Saitoh, Hidetoshi ; Fukazawa, Yugo ; Inoue, Kazuhide ; Yawo, Hiromu ; Furue, Hidemasa ; Makoto, Tsuda. / Optogenetic activation of non-nociceptive aβ fibers induces neuropathic pain-like sensory and emotional behaviors after nerve injury in rats. :: eNeuro. 2018 ; 巻 5, 番号 1.
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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 and produced an aversion to illumination. Thus, these findings provide the first evidence that optogenetic activation of primary afferent Aβ fibers in PNI rats produces excitation of Lamina I neurons and neuropathic pain-like behaviors that were resistant to morphine treatment. This approach may provide a new path for investigating circuits and behaviors of Aβ fiber-mediated neuropathic allodynia with sensory and emotional aspects after PNI and for discovering novel drugs to treat neuropathic pain.",
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AU - Tashima, Ryoichi

AU - Koga, Keisuke

AU - Sekine, Misuzu

AU - Kanehisa, Kensho

AU - Koro, Yuta

AU - Tominaga, Keiko

AU - Matsushita, Katsuyuki

AU - Saitoh, Hidetoshi

AU - Fukazawa, Yugo

AU - Inoue, Kazuhide

AU - Yawo, Hiromu

AU - Furue, Hidemasa

AU - Makoto, Tsuda

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N2 - 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 and produced an aversion to illumination. Thus, these findings provide the first evidence that optogenetic activation of primary afferent Aβ fibers in PNI rats produces excitation of Lamina I neurons and neuropathic pain-like behaviors that were resistant to morphine treatment. This approach may provide a new path for investigating circuits and behaviors of Aβ fiber-mediated neuropathic allodynia with sensory and emotional aspects after PNI and for discovering novel drugs to treat neuropathic pain.

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