Human visceral nociception: findings from translational studies in human tissue.
American journal of physiology. Gastrointestinal and liver physiology
MetadataShow full item record
Hockley, J., Smith, E. S. J., & Bulmer, D. (2018). Human visceral nociception: findings from translational studies in human tissue.. American journal of physiology. Gastrointestinal and liver physiology, 315 (4), G464-G472. https://doi.org/10.1152/ajpgi.00398.2017
Peripheral sensitisation of nociceptors during disease has long been recognised as a leading cause of inflammatory pain. However, a growing body of data generated over the last decade has led to the increased understanding that peripheral sensitisation is also an important mechanism driving abdominal pain in highly prevalent functional bowel disorders, in particular irritable bowel syndrome (IBS). As such, the development of drugs that target pain-sensing nerves innervating the bowel, has the potential to be a successful analgesic strategy for the treatment of abdominal pain in both organic and functional gastrointestinal diseases. Despite the success of recent peripherally restricted approaches for the treatment of IBS, not all drugs that have shown efficacy in animal models of visceral pain have reduced pain end points in clinical trials of IBS patients, suggesting innate differences in the mechanisms of pain processing between rodents and humans, and in particular, how we model disease states. To address this gap in our understanding of peripheral nociception from the viscera and the body in general, several groups have developed experimental systems to study nociception in isolated human tissue and neurons; the findings of which we discuss in this review. Studies of human tissue identify a repertoire of human primary afferent subtypes comparable to rodent models including a nociceptor population, the targeting of which will shape future analgesic development efforts. Detailed mechanistic studies in human sensory neurones combined with unbiased RNA sequencing approaches have revealed fundamental differences in not only receptor/channel expression, but also peripheral pain pathways.
Intestines, Ganglia, Spinal, Nociceptors, Animals, Humans, Irritable Bowel Syndrome, Translational Medical Research, Nociception
Rosetrees Trust (A1296)
External DOI: https://doi.org/10.1152/ajpgi.00398.2017
This record's URL: https://www.repository.cam.ac.uk/handle/1810/284195