title: Activation of lumbar spinal wide-dynamic range neurons by a sanshool derivative.
abstract: 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.
authors.affiliation: Department of Neurobiology, Physiology and Behavior, University of California, Davis, 1 Shields Avenue, Davis, CA 95616. eecarstens@ucdavis.edu).
authors.forename: Carolyn M
authors.initials: CM
authors.lastname: Sawyer
authors.forename: Mirela Iodi
authors.initials: MI
authors.lastname: Carstens
authors.forename: Christopher T
authors.initials: CT
authors.lastname: Simons
authors.forename: Jay
authors.initials: J
authors.lastname: Slack
authors.forename: T Scott
authors.initials: TS
authors.lastname: McCluskey
authors.forename: Stefan
authors.initials: S
authors.lastname: Furrer
authors.forename: E
authors.initials: E
authors.lastname: Carstens
mesh_terms: D000200:Action Potentials / Q000187:drug effects; D000577:Amides / Q000494:pharmacology*; D000818:Animals; D002211:Capsaicin / Q000494:pharmacology; D003080:Cold Temperature; D004305:Dose-Response Relationship, Drug; D006358:Hot Temperature; D017879:Isothiocyanates / Q000494:pharmacology; D008161:Lumbosacral Region; D008297:Male; D017711:Nonlinear Dynamics; D010812:Physical Stimulation / Q000379:methods; D051381:Rats; D017207:Rats, Sprague-Dawley; D011984:Sensory Receptor Cells / Q000145:classification / Q000187:drug effects*; D018689:Sensory System Agents / Q000494:pharmacology; D012684:Sensory Thresholds / Q000187:drug effects / Q000502:physiology; D012867:Skin / Q000294:innervation; D013116:Spinal Cord / Q000166:cytology*
chemical_list: D000577:Amides; D017879:Isothiocyanates; D018689:Sensory System Agents; C100574:sanshool; C041942:2,3,4-tri-O-acetylarabinopyranosyl isothiocyanate; D002211:Capsaicin