Peptides derived from the venoms of marine cone snails have attracted recent attention as potential therapeutic agents for the treatment of chronic pain.Although conotoxins share the attractive features ofpeptides in general of having exquisite selectivity and potency for particular ion channels,membrane receptors or transporters,they also share the general disadvantages of peptides of short biological half-lives and poor oral bioavailability.Cyclisation has been used in the past as a strategy in the pharmaceutical industry for stabilising and locking the conformation of small peptides of 5-12 amino acids.This cyclisation strategy can also be applied to conotoxins to produce additional stabilisation with the potential to dramatically increase the therapeutic potential of these molecules.In this study,we describe the development of a conotoxin analogue that has potent analgesic activity in the chronic constriction injury model of neuropathic pain in rats when administered orally.This result demonstrates the effectiveness of the cyclisation approach for the stabilisation ofpeptide therapeutics.Neuropathic pain is caused by damage to the nervous system and is among the most severe forms of chronic pain.Although there are medications available for the treatment of neuropathic pain,these are effective in only 40-60% of patients and there is a great need for new effective treatments for this condition.