The invention features a method for inhibiting one or more
voltage-gated
ion channels in a
cell by contacting the
cell with (i) a first compound that activates a channel-forming
receptor that is present on nociceptors and / or pruriceptors; and (ii) a second compound that inhibits one or more
voltage-gated
ion channels when applied to the internal face of the channels but does not substantially inhibit said channels when applied to the external face of the channels, wherein the second compound is capable of entering nociceptors or pruriceptors through the channel-forming
receptor when the
receptor is activated. The invention also features a
quaternary amine derivative or other permanently or transiently charged derivative of a compound that inhibits one or more
voltage-gated
ion channels when applied to the internal face of the channels but does not substantially inhibit said channels when applied to the external face of the channels.