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The Journal of Neuroscience, September 12, 2007, 27(37):10007-10014; doi:10.1523/JNEUROSCI.2862-07.2007

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Behavioral/Systems/Cognitive
The Itch-Producing Agents Histamine and Cowhage Activate Separate Populations of Primate Spinothalamic Tract Neurons

Steve Davidson,^1,3 Xijing Zhang,¹ Chul H. Yoon,¹ Sergey G. Khasabov,² Donald A. Simone,^2,3 and Glenn J. Giesler, Jr^1,3

¹Department of Neuroscience, Medical School, ²Department of Diagnostic and Biological Sciences, School of Dentistry, and ³Graduate Program in Neuroscience, University of Minnesota, Minneapolis, Minnesota 55455

Correspondence should be addressed to Glenn J. Giesler Jr, Department of Neuroscience, 6-145 Jackson Hall, University of Minnesota, Minneapolis, MN 55455. Email: giesler{at}umn.edu

Itch is an everyday sensation, but when associated with disease or infection it can be chronic and debilitating. Several forms of itch can be blocked using antihistamines, but others cannot and these constitute an important clinical problem. Little information is available on the mechanisms underlying itch that is produced by nonhistaminergic mechanisms. We examined the responses of spinothalamic tract neurons to histaminergic and, for the first time, nonhistaminergic forms of itch stimuli. Fifty-seven primate spinothalamic tract (STT) neurons were identified using antidromic activation techniques and examined for their responses to histamine and cowhage, the nonhistaminergic itch-producing spicules covering the pod of the legume Mucuna pruriens. Each examined neuron had a receptive field on the hairy skin of the hindlimb and responded to noxious mechanical stimulation. STT neurons were tested with both pruritogens applied in a random order and we found 12 that responded to histamine and seven to cowhage. Each pruritogen-responsive STT neuron was activated by the chemical algogen capsaicin and two-thirds responded to noxious heat stimuli, demonstrating that these neurons convey chemical, thermal, and mechanical nociceptive information as well. Histamine or cowhage responsive STT neurons were found in both the marginal zone and the deep dorsal horn and were classified as high threshold and wide dynamic range. Unexpectedly, histamine and cowhage never activated the same cell. Our results demonstrate that the spinothalamic tract contains mutually exclusive populations of neurons responsive to histamine or the nonhistaminergic itch-producing agent cowhage.

Key words: pruritus; spinal cord; electrophysiology; pain; capsaicin; dorsal horn

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Received June 22, 2007; revised Aug. 2, 2007; accepted Aug. 2, 2007.

Correspondence should be addressed to Glenn J. Giesler Jr, Department of Neuroscience, 6-145 Jackson Hall, University of Minnesota, Minneapolis, MN 55455. Email: giesler{at}umn.edu

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				V. B. Reddy, A. O. Iuga, S. G. Shimada, R. H. LaMotte, and E. A. Lerner Cowhage-Evoked Itch Is Mediated by a Novel Cysteine Protease: A Ligand of Protease-Activated Receptors J. Neurosci., April 23, 2008; 28(17): 4331 - 4335. [Abstract] [Full Text] [PDF]

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