The spinal dorsal horn (SDH) receives somatosensory inputs from the periphery and descending pain modulatory inputs from several brain regions including the locus coeruleus (LC). Recent progress has been made in understanding neuronal circuits in the SDH, but the role of astrocytes, one type of glial cells, in somatosensory information processing and behavior under physiological conditions is entirely unknown. Here, by establishing a method to monitor SDH astrocytic activities using an in vivo Ca2+ imaging technique, we revealed that superficial SDH astrocytes were activated following noxious stimulation by intraplantar capsaicin injection and that the astrocytic responses required activation of a1A-adrenergic receptors (a1A-AR) through descending noradrenergic signaling from the LC. Pharmacological inhibition of LC–SDH noradrenergic pathway and selective knockdown of a1A-AR in superficial SDH astrocytes prevented capsaicin-induced pain hypersensitivity to light mechanical stimulation. Moreover, pharmacological activation of a1-AR in superficial SDH astrocytes was sufficient to induce mechanical pain hypersensitivity. Our findings demonstrate for the first time the potential ability of superficial SDH astrocytes to modulate mechanosensory behavior as a non-neuronal gate for the descending noradrenergic pathway from the brain.

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