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_1A-adrenoceptors (α_1A-ARs) through descending noradrenergic signaling from the locus coeruleus. Intrathecal norepinephrine induced mechanical pain hypersensitivity via α_1A-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_1A-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.

星形胶质细胞是 CNS 功能的关键调节器，并且被认为在发育中的大脑和脊髓中是异质的。在这里，我们确定了位于成人脊髓背角 (SDH) 浅层的星形胶质细胞群，其基因由Hes5定义。体内成像显示，足底内注射辣椒素的有害刺激可通过 α _{1A -}肾上腺素能受体 (α _1A -ARs) 通过降低来自蓝斑的去甲肾上腺素能信号传导激活Hes5 ⁺ SDH 星形胶质细胞。鞘内注射去甲肾上腺素通过Hes5 ⁺星形胶质细胞中的α _1A -ARs诱导机械性疼痛超敏反应，以及Hes5 的化学刺激⁺ SDH 星形胶质细胞足以产生超敏反应。此外，通过抑制Hes5 ⁺星形胶质细胞上的蓝斑下降位点 - 去甲肾上腺素能信号传导来防止辣椒素诱导的机械超敏反应。此外，在慢性疼痛模型中，Hes5 ⁺星形胶质细胞中的α _1A -ARs是确定度洛西汀镇痛作用的关键调节因子。我们的研究结果确定了一个表面的 SDH 选择性星形胶质细胞群，它控制机械感觉行为的降去甲肾上腺素能控制。