Experimental models of stress and pain: do they help to develop new therapies?
The majority of functional gastrointestinal disorders are characterised by recurrent abdominal pain, with stress playing an important role in first onset and exacerbation of existing symptoms. These disorders are currently defined by symptom criteria, while their pathophysiology remains controversial and incompletely understood. Modeling these disorders in humans and animals has been difficult. While some of the models have adequate face and construct validity, the predictive validity of most of the models has been disappointing, which has put into question the traditional modeling approach. Similar problems have been encountered in drug development for pain and psychiatric disorders. New approaches have been proposed in the form of reverse translation, which include better characterisation of biological intermediate phenotypes in human disease which can be modeled in humans and in animals. Continuation of the current approach focusing on complex clinical phenotypes is likely to be ineffective for the development of novel and effect treatments.
Bradesi
Sylvie
S
UCLA Center for Neurobiology of Stress, Department of Medicine, David Geffen School of Medicine at UCLA, Los Angeles, CA 90073, USA. sbradesi@ucla.edu
Mayer
Emeran A
EA
D000818:Animals; D004195:Disease Models, Animal; D055808:Drug Discovery; D005772:Gastrointestinal Transit / Q000502:physiology; D006801:Humans; D043183:Irritable Bowel Syndrome / Q000188:drug therapy / Q000503:physiopathology; D059408:Pain Management; D013315:Stress, Psychological / Q000628:therapy*