BB2 bombesin receptor-expressing spinal neurons transmit herpes-associated itch by BB2 receptor-independent signaling.

Although spinal neurons expressing BB2 bombesin receptors are suggested to be involved in itch transmission, their role in pathological itch remains unknown. Because itch is often observed in patients with herpes zoster, we examined the role of BB2 receptor-expressing spinal neurons in herpes-associated itch in mice. Transdermal inoculation of human herpes virus 1 on the midflank produced herpes zoster-like skin lesions and caused the mice to scratch (itch-related behavior) and lick (pain-related behavior) the affected skin. Ablation of BB2 receptor-expressing spinal neurons by intrathecal treatment with a bombesin-saporin conjugate decreased the scratching but not the licking. Intrathecal administration of the BB2 receptor antagonist Leu13-ψ-(CH2NH)Leu14-bombesin decreased BB2 receptor agonist GRP(18-27)-induced scratching in naive mice but not herpes-associated scratching. The present results suggest that BB2 receptor-expressing spinal neurons transmit herpes-associated itch by BB2 receptor-independent signaling.