Targeting ion channels involved in nociception is currently being investigated for the treatment of pain. Human genetic studies have demonstrated that patients with null mutations in the voltage-gated sodium channel Nav1.7 were resistant to pain suggesting that Nav1.7 could be a target for the development of novel analgesic. ProTx-II, a peptide toxin belonging to the inhibitory cystine knot (ICK) family, was shown to selectively block the Nav1.7 channel but lacked in vivo efficacy.