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

Anna Kanemaru-Kawazoe1, Hideki Funahashi1, Yoichiro Kogoh1

  • 1Department of Psychiatry, Division of Clinical Neuroscience, Faculty of Medicine, University of Miyazaki, 5200 Kihara, Kiyotake, Miyazaki city, Miyazaki 889-1692, Japan.

Neuroscience Research
|August 29, 2025
PubMed

Insights

Orexin A (OX-A) effectively reduces itch responses to histamine and chloroquine (CQ) by acting on orexin receptors. This suggests orexin peptides play a key role in modulating itch signaling pathways.

Area of Science:

  • Neuroscience
  • Pruritus Research
  • Itch Signaling Pathways

Background:

  • Orexin peptides are known to influence pain (nociception).
  • Their specific role in itch (pruriception) processing remains largely unexplored.
  • Understanding orexin's function in itch could reveal novel therapeutic targets.

Purpose of the Study:

  • To investigate the role of orexin A (OX-A) and orexin B (OX-B) in itch processing.
  • To determine the involvement of orexin receptors (OX1 and OX2) in mediating these effects.
  • To elucidate how orexin peptides modulate itch signals induced by histamine and chloroquine (CQ).

Main Methods:

  • Administration of OX-A and OX-B prior to histamine or CQ injections in a model system.
  • Assessment of scratching behavior and neuronal activation (c-Fos expression).
  • Use of orexin receptor 1 (OX1) and orexin receptor 2 (OX2) antagonists (SB334867, JNJ10397049) and an OX2 agonist (YNT185) to probe receptor involvement.

Main Results:

  • OX-A, but not OX-B, significantly reduced scratching events and c-Fos expression induced by histamine and CQ.
  • The anti-pruritic effects of OX-A were reversed by OX1 and OX2 antagonists, indicating receptor mediation.
  • An OX2 receptor agonist (YNT185) attenuated histamine-induced, but not CQ-induced, itch and neuronal activation.

Conclusions:

  • Orexin A demonstrates significant anti-pruritic effects, modulating itch processing.
  • Histamine and CQ-induced itch signals are differentially regulated by OX1 and OX2 receptors.
  • Orexin signaling represents a potential pathway for controlling specific types of itch.

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