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J Neurophysiol 101: 1742-1748, 2009. First published January 21, 2009; doi:10.1152/jn.91311.2008
0022-3077/09 $8.00
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Activation of Lumbar Spinal Wide-Dynamic Range Neurons by a Sanshool Derivative

Carolyn M. Sawyer1, Mirela Iodi Carstens1, Christopher T. Simons2, Jay Slack2, T. Scott McCluskey2, Stefan Furrer2 and E. Carstens1

1Department of Neurobiology, Physiology and Behavior, University of California, Davis, Davis, California; and 2Givaudan Flavors Corporation, Cincinnati, Ohio

Submitted 10 December 2008; accepted in final form 24 January 2009

The enigmatic sensation of tingle involves the activation of primary sensory neurons by hydroxy-{alpha}-sanshool, a tingly agent in Szechuan peppers, by inhibiting two-pore potassium channels. Central mechanisms mediating tingle sensation are unknown. We investigated whether a stable derivative of sanshool—isobutylalkenyl amide (IBA)—excites wide-dynamic range (WDR) spinal neurons that participate in transmission of chemesthetic information from the skin. In anesthetized rats, the majority of WDR and low-threshold units responded to intradermal injection of IBA in a dose-related manner over a >5-min time course and exhibited tachyphylaxis at higher concentrations (1 and 10%). Almost all WDR and low-threshold units additionally responded to the pungent agents mustard oil (allyl isothiocyanate) and/or capsaicin, prompting reclassification of the low-threshold cells as WDR. The results are discussed in terms of the functional role of WDR neurons in mediating tingle sensation.


Address for reprint requests and other correspondence: E. Carstens, Department of Neurobiology, Physiology and Behavior, University of California, Davis, 1 Shields Avenue, Davis, CA 95616 (E-mail: eecarstens{at}ucdavis.edu)







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