1-isoquinolin-5-yl-3-(4-trifluoromethyl-benzyl)-urea and sanshool

Hydroxy-alpha-sanshool, the active ingredient in plants of the prickly ash plant family, induces robust tingling paresthesia by activating a subset of somatosensory neurons. However, the subtypes and physiological function of sanshool-sensitive neurons remain unknown. Here we use the ex vivo skin-nerve preparation to examine the pattern and intensity with which the sensory terminals of cutaneous neurons respond to hydroxy-alpha-sanshool. We found that sanshool excites virtually all D-hair afferents, a distinct subset of ultrasensitive light-touch receptors in the skin and targets novel populations of Abeta and C fiber nerve afferents. Thus, sanshool provides a novel pharmacological tool for discriminating functional subtypes of cutaneous mechanoreceptors. The identification of sanshool-sensitive fibers represents an essential first step in identifying the cellular and molecular mechanisms underlying tingling paresthesia that accompanies peripheral neuropathy and injury.

Topics: Action Potentials; Amides; Animals; Animals, Newborn; Capsaicin; Cells, Cultured; gamma-Aminobutyric Acid; In Vitro Techniques; Isoquinolines; Mechanoreceptors; Mice; Mice, Inbred C57BL; Mustard Plant; Nerve Fibers; Nerve Growth Factors; Neural Conduction; Neurons, Afferent; Paresthesia; Plant Oils; Sensory Receptor Cells; Sensory System Agents; Skin; Statistics, Nonparametric; Touch; Trigeminal Ganglion; Urea