Alkylamides that produce tingling paresthesia activate tactile and thermal trigeminal neurons.

Alkylamides isolated from the fruit of Xanthoxylum, Szechuan pepper, produce a strong tingling sensation in the mouth. In order to determine the peripheral basis of this sensation, extracellular nerve recordings were obtained from the lingual nerve of rats. The primary pungent compound, hydroxy-alpha-sanshool (HO-alpha-S), altered the levels of spontaneous activity in cool-sensitive fibers as well as inducing activity in tactile fibers, cold nociceptors and silent fibers that were insensitive to innocuous thermal or tactile stimuli. Moreover, tactile or thermal sensitivity was induced in fibers that were initially insensitive to touch or cooling. The neuronal distribution of sensitivities to capsaicin and to HO-alpha-S indicate that this compound affects neurons mediating innocuous sensations. HO-alpha-S may be useful as a model stimulus for studies of paresthesia.