Spinal Glycine Receptor Alpha 3 Cells Communicate Sensations of Chemical Itch in Hairy Skin

Abstract

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 inGlra3-Cre female and male mice.Glra3-Cre(+) neurons expressGlra3, are located mainly in laminae III–VI, and respond to glycine. Chemogenetic activation of spinalGlra3-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 expressGlra3, further supporting the phenotype. Retrograde tracing revealed that spinalGlra3-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 spinalGlra3(+) neurons contribute to acute communication of compound 48/80- and chloroquine-induced itch in hairy skin.