Characterization of itch-related behavior and physiology of trigeminothalamic tract neurons in rats, including the role of opioids

Abstract

The sensations of itch and pain are processed by the same neural systems, yet produce distinct perceptual experiences and behaviors. Therefore, it is important to study itch in animal models which exhibit differential behaviors to itchy versus painful stimuli. In rodents, application of pruritogens to the face produces scratching with the hindlimb while application of algogens produces wiping with the forelimb. Here, we use the face model in rats to characterize behaviors produced by the peripheral pruritogen serotonin, the central pruritogen morphine, and combined delivery of these two drugs. Intradermal injection of serotonin or intracisternal injection of morphine elicits dose-dependent scratching. Serotonin-induced scratching is attenuated by naloxone while serotonin-induced wiping is attenuated by morphine. Combined delivery of serotonin and morphine results in a superadditive increase in scratching. In humans, itch and pain sensations require spinal projection neurons which terminate in somatosensory thalamic nuclei. Here, we characterize responses to pruritogens in trigeminothalamic tract (VTT) neurons in rats which may be involved in carrying information about facially-applied pruritogens to the forebrain for producing the itch sensation and related behaviors. VTT neurons respond to a variety of pruritogens; all pruriceptive VTT neurons also respond to noxious mechanical and/or thermal input. We show that intrathecal application of morphine excites pruriceptive VTT neurons and inhibits nociceptive-only VTT neurons. Responses to serotonin are increased in the presence of morphine, providing a possible explanation for the superadditive increase in facial scratching seen upon combined delivery of these two drugs. Our results provide evidence against a labeled line for itch information within the central nervous system and suggest that the brain may decode itch signaling via spike patterns or a population code. These experiments lay the groundwork for use of the face model and the VTT system in rats for the future study of salient questions which remain in the field of itch.