The opposing roles of hypothalamic orexin neurons in pain and itch neural regulation

Abstract

Pain and itch are recognized as antagonistic sensations; pain suppresses itch and inhibition of pain generates itch. There is still a lack of evidence about the neural processing of the pain-itch interaction in the central nervous system. To reveal the such mechanism, we focused on the orexin (ORX) neurons in the lateral hypothalamus, which mediate various “defense responses” when animals confront stressors. We found that the pruritogen-induced scratching behaviors were significantly inhibited in ORX-neuron-ablated (ORX-abl) mice. The exaggerated pain behavior and attenuated itch behavior observed in ORX-abl mice indicated that ORX neurons modulate pain and itch in an opposite way, i.e., pain relief and itch exacerbation. In addition, most of the ORX neurons responded to both pain and itch input. Our results suggest that ORX neurons inversely regulate pain- and itch-related behaviors, which could be understood as a defense response to cope with stress environment.