Extracts of Echinacea plants induce intense tingling paresthesia and numbing analgesia when applied orally. Currently, there is little information regarding the cellular or molecular mechanisms by which Echinacea produces its somatosensory effects. We characterized the ability of Echinacea extracts to activate somatosensory neurons in vitro. Crude extracts induce a rise in intracellular calcium in a subset of somatosensory neurons (49.0±6.2%), as measured by ratiometric calcium imaging. In addition, application of Echinacea extract during whole-cell current-clamp recording triggers depolarization of the resting membrane potential, followed by action potential firing. Both the crude extract and the purified alkylamide, Dodeca-2E, 4E- dienoic acid isobutylamide (E2), activate a unique subset of somatosensory neurons that includes a large population of putative light touch receptors. Whole-cell voltage clamp recording shows that E2 blocks a background potassium current (28.0±3.8% inhibition at 50mV; reversal potential = −51.8,±2.5), in 56% of somatosensory neurons. Interestingly, we find that E2 also inhibits voltage gated sodium currents in 57% of neurons (44.6±5.1% inhibition at x −20mV). We propose a model in which Dodeca-2E, 4E- dienoic acid isobutylamide induces tingling paresthesia by inhibition of background potassium currents and numbing analgesia by blocking voltage-gated sodium channels.