Experimental Models of Stress and Pain: Do They Help to Develop New Therapies?

Abstract

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.

Advances in Imaging the Brain–Gut Axis: Functional Gastrointestinal Disorders

“…One of the reasons for this translational failure may be the predominance of higher cortical modulation of subcortical systems involved in the generation of IBS symptoms and the difficulty in studying homologous modulatory systems in rodent models. 2 Imaging the brain allows us to evaluate not only the input from the periphery via the homeostatic (visceral) afferent system in the brain, but also the role of emotional and cognitive factors in the modulation of the afferent input. Neuroimaging can provide a noninvasive way to index the central response of humans to symptoms, and to a variety of stimuli including medications, symptom-like stressors, and psychosocial stress.…”

Stress and visceral pain: From animal models to clinical therapies

“…Some commonly used animal models showed the modulation of visceral pain to CRD by acute or chronic stressors presenting good face and construct validity, however, their predictive validity in humans is either unknown or has been unsatisfying in clinical trials (Bradesi and Mayer, 2009; Holschneider et al, 2011; Mayer et al, 2008). The use of novel non-invasive techniques to assess visceral pain such as intraluminal colonic pressure (Larauche et al, 2009a; Larauche et al, 2010a) by allowing for the monitoring of stress-induced visceral analgesia, may open new venues to deepen our understanding of stress-related analgesic pain pathways in the viscera.…”

“…The use of novel non-invasive techniques to assess visceral pain such as intraluminal colonic pressure (Larauche et al, 2009a; Larauche et al, 2010a) by allowing for the monitoring of stress-induced visceral analgesia, may open new venues to deepen our understanding of stress-related analgesic pain pathways in the viscera. Novel strategies such as identification and characterization of endophenotypes in IBS patients, followed by reverse translation of these endophenotypes for pharmacological studies in rodents, have also been recently suggested (Bradesi and Mayer, 2009; Holschneider et al, 2011; Mayer et al, 2008). …”

Predictive validity of behavioural animal models for chronic pain

“…We will here review some commonly used models from this perspective. More comprehensive discussion of animal models can be found in a number of recent reviews (Decosterd and Berta, 2008; Di Paola and Cuzzocrea, 2008; Jeong and Holden, 2008; Pacharinsak and Beitz, 2008; Authier et al ., 2009; Bradesi and Mayer, 2009; Sandkühler, 2009; Sorkin and Yaksh, 2009; Colleoni and Sacerdote, 2010).…”