Glycinergic neurons regulate nociceptive and pruriceptive signaling in the spinal cord, but the identity and role of the glycine-regulated neurons are not fully known. Herein, we have characterized spinal glycine receptor alpha 3 (Glra3) subunit-expressing neurons in Glra3-Cre female and male mice. Glra3-Cre(+) neurons express Glra3, are located mainly in laminae III–VI, and respond to glycine. Chemogenetic activation of spinal Glra3-Cre(+) neurons induced biting/licking, stomping, and guarding behaviors, indicative of both a nociceptive and pruriceptive role for this population. Chemogenetic inhibition did not affect mechanical or thermal responses but reduced behaviors evoked by compound 48/80 and chloroquine, revealing a pruriceptive role for these neurons. Spinal cells activated by compound 48/80 or chloroquine express Glra3, further supporting the phenotype. Retrograde tracing revealed that spinal Glra3-Cre(+) neurons receive input from afferents associated with pain and itch, and dorsal root stimulation validated the monosynaptic input. In conclusion, these results show that spinal Glra3(+) neurons contribute to acute communication of compound 48/80- and chloroquine-induced itch in hairy skin.

甘氨酸能神经元调节脊髓中的伤害性和瘙痒性信号传导，但甘氨酸调节神经元的身份和作用尚不完全清楚。在此，我们对Glra3 -Cre 雌性和雄性小鼠中脊髓甘氨酸受体 α 3 ( Glra3 ) 亚基表达神经元进行了表征。 Glra3 -Cre(+) 神经元表达Glra3，主要位于 III-VI 层，并对甘氨酸有反应。脊髓Glra3 -Cre(+) 神经元的化学遗传学激活诱导咬/舔、跺脚和守卫行为，表明该群体具有伤害性和瘙痒性作用。化学抑制不会影响机械或热反应，但会减少化合物 48/80 和氯喹引起的行为，揭示了这些神经元的瘙痒作用。被化合物 48/80 或氯喹激活的脊髓细胞表达Glra3，进一步支持了该表型。逆行追踪显示脊髓Glra3 -Cre(+) 神经元接收来自与疼痛和瘙痒相关的传入神经的输入，并且背根刺激验证了单突触输入。总之，这些结果表明脊髓Glra3 (+) 神经元有助于化合物 48/80 和氯喹引起的多毛皮肤瘙痒的急性通讯。