Activation of spinal dorsal horn astrocytes by noxious stimuli involves descending noradrenergic signaling

Astrocytes are critical regulators of neuronal function in the central nervous system (CNS). We have previously shown that astrocytes in the spinal dorsal horn (SDH) have increased intracellular Ca 2+ levels following intraplantar injection of the noxious irritant, formalin. However, the underlying mechanisms remain unknown. We investigated these mechanisms by focusing on the role of descending noradrenergic (NAergic) signaling because our recent study revealed the essential role of the astrocytic Ca 2+ responses evoked by intraplantar capsaicin. Using in vivo SDH imaging, we found that the Ca 2+ level increase in SDH astrocytes induced by intraplantar formalin injection was suppressed by ablation of SDH-projecting locus coeruleus (LC)-NAergic neurons. Furthermore, the formalin-induced Ca 2+ response was dramatically decreased by the loss of α 1A -adrenaline receptors (ARs) in astrocytes located in the superficial laminae of the SDH. Moreover, similar inhibition was observed in mice pretreated intrathecally with an α 1A -AR-specific antagonist. Therefore, activation of α 1A -ARs via descending LC-NAergic signals may be a common mechanism underlying astrocytic Ca 2+ responses in the SDH evoked by noxious stimuli, including chemical irritants.