A tingling sanshool derivative excites primary sensory neurons and elicits nocifensive behavior in rats

Amanda H. Klein, Carolyn M. Sawyer, Karen L. Zanotto, Margaret A. Ivanov, Susan Cheung, Mirela Iodi Carstens, Stephan Furrer, Christopher T. Simons, Jay P. Slack, Earl Carstens

Research output: Contribution to journalArticle

27 Scopus citations

Abstract

Szechuan peppers contain hydroxy--sanshool that imparts desirable tingling, cooling, and numbing sensations. Hydroxy--sanshool activates a subset of sensory dorsal root ganglion (DRG) neurons by inhibiting two-pore potassium channels. We presently investigated if a tingle-evoking sanshool analog, isobutylalkenyl amide (IBA), excites rat DRG neurons and, if so, if these neurons are also activated by agonists of TRPM8, TRPA1, and/or TRPV1. Thirty-four percent of DRG neurons tested responded to IBA, with 29% of them also responding to menthol, 29% to cinnamic aldehyde, 66% to capsaicin, and subsets responding to two or more transient receptor potential (TRP) agonists. IBA-responsive cells had similar size distributions regardless of whether they responded to capsaicin or not; cells only responsive to IBA were larger. Responses to repeated application of IBA at a 5-min interstimulus interval exhibited self-desensitization (tachyphylaxis). Capsaicin did not cross-desensitize responses to IBA to any greater extent than the tachyphylaxis observed with repeated IBA applications. These findings are consistent with psychophysical observations that IBA elicits tingle sensation accompanied by pungency and cooling, with self-desensitization but little cross-desen-sitization by capsaicin. Intraplantar injection of IBA elicited nocifensive responses (paw licking, shaking-flinching, and guarding) in a dose-related manner similar to the effects of intraplantar capsaicin and serotonin. IBA had no effect on thermal sensitivity but enhanced mechanical sensitivity at the highest dose tested. These observations suggest that IBA elicits an unfamiliar aversive sensation that is expressed behaviorally by the limited response repertoire available to the animal.

Original languageEnglish (US)
Pages (from-to)1701-1710
Number of pages10
JournalJournal of Neurophysiology
Volume105
Issue number4
DOIs
StatePublished - Apr 2011

Keywords

  • Calcium imaging
  • Capsaicin
  • Dorsal root ganglion cell
  • Transient receptor potential channels

ASJC Scopus subject areas

  • Physiology
  • Neuroscience(all)

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    Klein, A. H., Sawyer, C. M., Zanotto, K. L., Ivanov, M. A., Cheung, S., Carstens, M. I., Furrer, S., Simons, C. T., Slack, J. P., & Carstens, E. (2011). A tingling sanshool derivative excites primary sensory neurons and elicits nocifensive behavior in rats. Journal of Neurophysiology, 105(4), 1701-1710. https://doi.org/10.1152/jn.00922.2010