Large molecules permeate heterologous cells and sensory neurons expressing TRPM8 ion channels. Molecule permeation induced by the TRPM8 agonist WS-12 is channel-dependent. The cell-impermeant lidocaine derivative QX-314 blocks voltage-gated Na+-channels in cells expressing activated TRPM8. Along with prior analysis of TRPV1 and TRPA1 channels, these data show that pain and somatosensory TRP channels can permeate large molecules.