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Spinal astrocytes in superficial laminae gate brainstem descending control of mechanosensory hypersensitivity.
Journal article

Spinal astrocytes in superficial laminae gate brainstem descending control of mechanosensory hypersensitivity.

  • Kohro Y Department of Life Innovation, Graduate School of Pharmaceutical Sciences, Kyushu University, Fukuoka, Japan.
  • Matsuda T Department of Life Innovation, Graduate School of Pharmaceutical Sciences, Kyushu University, Fukuoka, Japan.
  • Yoshihara K Department of Life Innovation, Graduate School of Pharmaceutical Sciences, Kyushu University, Fukuoka, Japan.
  • Kohno K Department of Life Innovation, Graduate School of Pharmaceutical Sciences, Kyushu University, Fukuoka, Japan.
  • Koga K Department of Life Innovation, Graduate School of Pharmaceutical Sciences, Kyushu University, Fukuoka, Japan.
  • Katsuragi R Department of Life Innovation, Graduate School of Pharmaceutical Sciences, Kyushu University, Fukuoka, Japan.
  • Oka T Department of Life Innovation, Graduate School of Pharmaceutical Sciences, Kyushu University, Fukuoka, Japan.
  • Tashima R Department of Life Innovation, Graduate School of Pharmaceutical Sciences, Kyushu University, Fukuoka, Japan.
  • Muneta S Department of Life Innovation, Graduate School of Pharmaceutical Sciences, Kyushu University, Fukuoka, Japan.
  • Yamane T Department of Life Innovation, Graduate School of Pharmaceutical Sciences, Kyushu University, Fukuoka, Japan.
  • Okada S Department of Life Innovation, Graduate School of Pharmaceutical Sciences, Kyushu University, Fukuoka, Japan.
  • Momokino K Department of Life Innovation, Graduate School of Pharmaceutical Sciences, Kyushu University, Fukuoka, Japan.
  • Furusho A Department of Drug Discovery and Evolution, Graduate School of Pharmaceutical Sciences, Kyushu University, Fukuoka, Japan.
  • Hamase K Department of Drug Discovery and Evolution, Graduate School of Pharmaceutical Sciences, Kyushu University, Fukuoka, Japan.
  • Oti T Department of Life Innovation, Graduate School of Pharmaceutical Sciences, Kyushu University, Fukuoka, Japan.
  • Sakamoto H Ushimado Marine Institute, Graduate School of Natural Science and Technology, Okayama University, Setouchi, Japan.
  • Hayashida K Department of Neurophysiology, Graduate School of Medicine, Akita University, Akita, Japan.
  • Kobayashi R Laboratory of Genome Science, Biosignal Genome Resource Center, Institute for Molecular and Cellular Regulation, Gunma University, Maebashi, Japan.
  • Horii T Laboratory of Genome Science, Biosignal Genome Resource Center, Institute for Molecular and Cellular Regulation, Gunma University, Maebashi, Japan.
  • Hatada I Laboratory of Genome Science, Biosignal Genome Resource Center, Institute for Molecular and Cellular Regulation, Gunma University, Maebashi, Japan.
  • Tozaki-Saitoh H Department of Life Innovation, Graduate School of Pharmaceutical Sciences, Kyushu University, Fukuoka, Japan.
  • Mikoshiba K Shanghai Institute for Advanced Immunochemical Studies, ShanghaiTech University, Shanghai, China.
  • Taylor V Department of Biomedicine, University of Basel, Basel, Switzerland.
  • Inoue K Department of Molecular and System Pharmacology, Graduate School of Pharmaceutical Sciences, Kyushu University, Fukuoka, Japan.
  • Tsuda M Department of Life Innovation, Graduate School of Pharmaceutical Sciences, Kyushu University, Fukuoka, Japan. tsuda@phar.kyushu-u.ac.jp.
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  • 2020-10-06
Published in:
  • Nature neuroscience. - 2020
General Neuroscience
English Astrocytes are critical regulators of CNS function and are proposed to be heterogeneous in the developing brain and spinal cord. Here we identify a population of astrocytes located in the superficial laminae of the spinal dorsal horn (SDH) in adults that is genetically defined by Hes5. In vivo imaging revealed that noxious stimulation by intraplantar capsaicin injection activated Hes5+ SDH astrocytes via α1A-adrenoceptors (α1A-ARs) through descending noradrenergic signaling from the locus coeruleus. Intrathecal norepinephrine induced mechanical pain hypersensitivity via α1A-ARs in Hes5+ astrocytes, and chemogenetic stimulation of Hes5+ SDH astrocytes was sufficient to produce the hypersensitivity. Furthermore, capsaicin-induced mechanical hypersensitivity was prevented by the inhibition of descending locus coeruleus-noradrenergic signaling onto Hes5+ astrocytes. Moreover, in a model of chronic pain, α1A-ARs in Hes5+ astrocytes were critical regulators for determining an analgesic effect of duloxetine. Our findings identify a superficial SDH-selective astrocyte population that gates descending noradrenergic control of mechanosensory behavior.
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  • English
Open access status
closed
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Persistent URL
https://sonar.ch/global/documents/139175
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