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The Journal of Neuroscience, May 20, 2009, 29(20):6691-6699; doi:10.1523/JNEUROSCI.6103-08.2009

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Behavioral/Systems/Cognitive
Activation of Superficial Dorsal Horn Neurons in the Mouse by a PAR-2 Agonist and 5-HT: Potential Role in Itch

Tasuku Akiyama, Austin W. Merrill, Mirela Iodi Carstens, and E. Carstens

Department of Neurobiology, Physiology, and Behavior, University of California, Davis, Davis, California 95616

Correspondence should be addressed to Prof. E. Carstens, Department of Neurobiology, Physiology, and Behavior, University of California, Davis, 1 Shields Avenue, Davis, CA 95616. Email: eecarstens{at}ucdavis.edu

Itch, an unpleasant sensation associated with the desire to scratch, is symptomatic of dermatologic and systemic disorders that often resist antihistamine treatment. Histamine-independent itch mediators include serotonin (5-HT) and agonists of the protease-activated receptor-2 (PAR-2). We used behavior, Fos immunohistochemistry, and electrophysiology to investigate if these mediators activate spinal dorsal horn neurons in a manner consistent with itch. Intradermal (id) injection of the PAR-2 agonist SLIGRL-NH₂ in the rostral back evoked bouts of directed hindlimb scratches over 20–30 min. Hindpaw injection of SLIGRL-NH₂ produced Fos staining in superficial dorsal horn which was then targeted for single-unit recording. Small id microinjections of SLIGRL-NH₂ or 5-HT identified responsive single units in the superficial dorsal horn of mice anesthetized with pentobarbital. Thirty-eight units characterized as wide dynamic range, nociceptive specific, or mechanically insensitive exhibited significantly increased firing after id SLIGRL-NH₂ for 9 min, to partial (25%) tachyphylaxis with repeated injection. A majority additionally responded to 5-HT (70%), mustard oil (79%), and capsaicin (71%). Seven units isolated with the 5-HT search stimulus exhibited significant and prolonged responses to 5-HT with tachyphylaxis to repeated injections. The majority also responded to SLIGRL-NH₂, mustard oil, and capsaicin. The prolonged responses of superficial dorsal horn neurons to SLIGRL-NH₂ and 5-HT suggest a role in signaling itch. However, their responsiveness to algogens is inconsistent with itch specificity. Alternatively, such neurons may signal itch, whereas noxious stimulus levels recruit these and a larger population of pruritogen-insensitive cells to signal pain which masks or occludes the itch signal.

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Received Dec. 22, 2008; revised Feb. 9, 2009; accepted March 4, 2009.

Correspondence should be addressed to Prof. E. Carstens, Department of Neurobiology, Physiology, and Behavior, University of California, Davis, 1 Shields Avenue, Davis, CA 95616. Email: eecarstens{at}ucdavis.edu

This article has been cited by other articles:

				T. Akiyama, M. I. Carstens, and E. Carstens Excitation of Mouse Superficial Dorsal Horn Neurons by Histamine and/or PAR-2 Agonist: Potential Role in Itch J Neurophysiol, October 1, 2009; 102(4): 2176 - 2183. [Abstract] [Full Text] [PDF]

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