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Papers of the Week

Papers: 3 Oct 2020 - 9 Oct 2020

Animal Studies

2020 Oct 05

Nat Neurosci

Editor's Pick

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


Kohro Y, Matsuda T, Yoshihara K, Kohno K, Koga K, Katsuragi R, Oka T, Tashima R, Muneta S, Yamane T, Okada S, Momokino K, Furusho A, Hamase K, Oti T, Sakamoto H, Hayashida K, Kobayashi R, Horii T, Hatada I, et al.
Nat Neurosci. 2020 Oct 05.
PMID: 33020652.


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 α-adrenoceptors (α-ARs) through descending noradrenergic signaling from the locus coeruleus. Intrathecal norepinephrine induced mechanical pain hypersensitivity via α-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, α-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.