Submitted on December 10, 2008
Revised on January 13, 2009
Accepted on January 14, 2009
Activation of lumbar spinal wide-dynamic range neurons by a sanshool derivative
Carolyn M Sawyer1, Mirela Iodi Carstens, Christopher T Simons2, Jay Slack2, T. Scott McCluskey2, Stefan Furrer2, and Earl Carstens1*
1 University of California, Davis
2 Givaudan Flavors Corp
* To whom correspondence should be addressed. E-mail: eecarstens{at}ucdavis.edu.
The enigmatic sensation of tingle involves the activation of primary sensory neurons by hydroxy-alpha-sanshool, a tingly agent in Szechuan peppers, by inhibiting 2-pore potassium channels. Central mechanisms mediating tingle sensation are unknown. We investigated if 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, AITC) 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.
