Achieving translation in models of visceral pain

The failure of drugs to modify pain end points in clinical trials for irritable bowel syndrome (IBS) highlights the knowledge gap that exists in the translation of efficacy in animal models of visceral pain into the clinic. Recent progress has been made towards improving the translation of visceral pain, particularly with regard to the activation of the sensory nerves which relay pain from the gut to the brain. This review will focus on studies which have identified the presence of an altered gastrointestinal and immune environment in IBS patients. The development of human gastrointestinal visceral afferent recordings has allowed direct comparison between sensory nerve studies in animals and human, as well as important advances in our understanding of the ion channels that underpin the changes in sensory nerve excitability.

► Need to improve translation of visceral pain demonstrated by recent IBS trials.
► Visceral pain relayed to the brain by visceral sensory nerve (afferents).
► Human supernatant studies have identified key mediators that excite visceral afferent in IBS.
► Development of in vitro human visceral afferent recordings allows direct translation of animal studies.
► Increased understanding of the ion channels underlying visceral afferents excitability.