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Updated: Sep 9, 2025

Cheek Injection Model for Simultaneous Measurement of Pain and Itch-related Behaviors
Published on: September 27, 2019
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.
Abstract:
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.
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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