Central mechanisms of itch transmission

Abstract Chronic itch is an unmet medical problem associated with numerous skin, immune, and nervous diseases. An imbalance of excitatory and inhibitory transmission of itch may contribute to the etiology of chronic itch. Understanding of inhibitory mechanisms of itch transmission is important for developing targeted anti-itch

therapies. The spinal cord interneurons expressing gastrin-releasing peptide receptor (GRPR) are crucial for itch transmission. Recent studies suggest that a subset of inhibitory neurons expressing neurokinin 3 receptor (TacR3) may be activated by pain for itch inhibition. We will employ an interdisciplinary approach to test the

hypothesis that TacR3 inhibitory neurons inhibit itch but not pain by inhibiting GRPR neurons. Aim 1 will determine anatomic and electrophysiological properties of TacR3 inhibitory neurons. Aim 2 will determine the role of spinal TacR3 inhibitory neurons in itch inhibition. Aim 3 will determine whether TacR3 neurons inhibit

GRPR neurons via GABAergic transmission. These studies should yield fundamental insight onto the spinal mechanisms by which itch is inhibited by pain.