The opposite roles of orexin neurons in pain and itch neural processing

• Published in: Peptides (New York, N.Y. : 1980) N.Y. : 1980), 2023-02, Vol.160, p.170928-170928, Article 170928
• Main Authors: Kaneko, Tatsuroh, Kuwaki, Tomoyuki
• Format: Article
• Language: English
• Subjects: Animals; Defense response; Hypothalamus - metabolism; Itch; Lateral hypothalamus; Neurons - metabolism; Orexin neuron; Orexins - metabolism; Pain; Pruritus; Stress
• ISSN: 0196-9781; 1873-5169
• DOI: 10.1016/j.peptides.2022.170928

Pain and itch are antagonistically regulated sensations; pain suppresses itch, and inhibition of pain enhances itch. Understanding the central neural circuit of antagonistic regulation between pain and itch is required to develop new therapeutics better to manage these two feelings in a clinical situation. However, evidence of the neural mechanism underlying the pain-itch interaction in the central nervous system (CNS) is still insufficient. To pave the way for this research area, our laboratory has focused on orexin (ORX) producing neurons in the hypothalamus, which is known as a master switch that induces various defense responses when animals face a stressful environment. This review article summarized the previous evidence and our latest findings to argue the neural regulation between pain and itch and the bidirectional roles of ORX neurons in processing these two sensations. i.e., pain relief and itch exacerbation. Further, we discussed the possible neural circuit mechanism for the opposite controlling of pain and itch by ORX neurons. Focusing on the roles of ORX neurons would provide a new perspective to understand the antagonistic regulation of pain and itch in CNS. •Pain and itch are antagonistically regulated sensations.•The neural mechanism of the interaction between pain and itch in the central nervous system (CNS) is still unclear.•Orexin neurons play opposite roles in pain and itch neural processing: inhibiting pain but facilitating itch.•Focusing on the orexin neurons provides a new perspective to understanding the antagonistic regulation of pain and itch in the CNS.