Itch is a major clinical problem from which relief is sought by patients suffering from a variety of diseases and infections. Scratching and other noxious counter-stimuli block the perception of itch; however, neither the neural circuits nor the neurotransmitters involved in suppressing itch are known. Many spinothalamic tract (STT) neurons in the dorsal horn respond to pruritogens (itch producing agents) and are thought to link activity in primary afferent pruriceptors to perceptual experience. Preliminary findings in the monkey indicate that noxious counter-stimuli can inhibit the discharge of STT neurons during a response to a pruritic agent. Therefore, the major goal of this proposed study is to determine the mechanisms responsible for the inhibition of pruritogen evoked responses in primate STT neurons. Extracellular recordings will be performed from single, antidromically identified STT neurons determined to be responsive to the itch producing agent histamine or cowhage (a non-histaminergic and therefore clinically relevant pruritogen).
The specific aims of this project are to determine: 1) whether a descending pathway from supraspinal sites is involved in inhibiting pruritogen evoked responses of STT neurons; and 2) whether the inhibition of a pruritogen evoked STT response requires the inhibitory neurotransmitters GABA and/or glycine. These studies will contribute to an overall understanding of itch and begin to address the neural mechanisms of its control. For most everyday itches, a quick scratch will abolish the aversive sensation; however, itch caused by disease or infection is one of the leading symptoms driving individuals to seek professional medical treatment.
The aim of this research proposal is to determine how the nervous system controls itch. Knowledge about the brain and spinal cord mechanisms involved in the control of itch may lead to more effective treatments for itch and improve public health. ? ? ?

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Predoctoral Individual National Research Service Award (F31)
Project #
5F31NS059199-02
Application #
7388995
Study Section
Special Emphasis Panel (ZRG1-F02B-G (20))
Program Officer
Gnadt, James W
Project Start
2007-03-12
Project End
2010-03-11
Budget Start
2008-03-12
Budget End
2009-03-11
Support Year
2
Fiscal Year
2008
Total Cost
$31,091
Indirect Cost
Name
University of Minnesota Twin Cities
Department
Neurosciences
Type
Schools of Medicine
DUNS #
555917996
City
Minneapolis
State
MN
Country
United States
Zip Code
55455
Davidson, Steve; Zhang, Xijing; Khasabov, Sergey G et al. (2012) Pruriceptive spinothalamic tract neurons: physiological properties and projection targets in the primate. J Neurophysiol 108:1711-23
Davidson, Steve; Truong, Hai; Giesler Jr, Glenn J (2010) Quantitative analysis of spinothalamic tract neurons in adult and developing mouse. J Comp Neurol 518:3193-204
Davidson, Steve; Truong, Hai; Nakagawa, Yasushi et al. (2010) A microinjection technique for targeting regions of embryonic and neonatal mouse brain in vivo. Brain Res 1307:43-52
Davidson, Steve; Zhang, Xijing; Khasabov, Sergey G et al. (2009) Relief of itch by scratching: state-dependent inhibition of primate spinothalamic tract neurons. Nat Neurosci 12:544-6
Davidson, Steve; Zhang, Xijing; Khasabov, Sergey G et al. (2008) Termination zones of functionally characterized spinothalamic tract neurons within the primate posterior thalamus. J Neurophysiol 100:2026-37
Davidson, Steve; Zhang, Xijing; Yoon, Chul H et al. (2007) The itch-producing agents histamine and cowhage activate separate populations of primate spinothalamic tract neurons. J Neurosci 27:10007-14