Role of orexin receptors in histamine- and chloroquine-induced pruriceptive processing

It is known that orexin peptides are involved in nociceptive processing, while little is known about the roles of these peptides in itch processing. To reveal the functions of orexin peptides in pruriceptive processing, orexin A (OX-A) and orexin B (OX-B) were applied before histamine or chloroquine (CQ). The administration of OX-A reduced the numbers of scratching events and c-Fos positive cells induced by histamine and CQ, but not OX-B. To clarify the involvement of orexin receptors in pruriceptive processing, OX-A was administered after the injection of an orexin receptor type 1 (OX₁) antagonist (SB334867) or an orexin receptor type 2 (OX₂) antagonist (JNJ10397049) before histamine and CQ injections. The attenuating effects of OX-A on histamine- and CQ-induced scratching events were reversed by JNJ1039 and SB334867, respectively. To confirm the role of OX₂ receptor, an OX₂ receptor agonist (YNT185) was applied before the injection of histamine or CQ. Scratching events and c-Fos expression induced by histamine, but not CQ, were attenuated by the pretreatment with YNT185. These results indicate that OX-A elicits the attenuating effects in pruriceptive processing and that itch signals induced by histamine and CQ appear to be differentially regulated by the OX₂ receptors and OX₁ receptors.