Human psychophysiological responses to visceral and somatic pain – the development of integrated, reproducible human pain phenotypes

PhDBackground Pain is the ubiquitous human experience, yet displays considerable inter- and intraindividual variability in health and disease. Many factors have been proposed to account for these differences. Pain activates a complex stress response, multiply determined through genetic, psychological, physiological and neuroanatomical factors. Chronic pain is a central defining characteristic of functional gastrointestinal disorders. They represent a major challenge for modern healthcare. An integrated understanding of the pathophysiology of these disorders remains to be elucidated. Aims To investigate human psychophysiological responses to visceral and somatic pain in health and disease, in order to develop multidimensional and reproducible pain phenotypes. Methods Study 1, in healthy volunteers, investigated personality traits, hypothalamic pituitary adrenal axes and selective novel non-invasive measures of autonomic tone in response to visceral and somatic pain. Study 2 examined the salience of genetic polymorphisms of the serotonin transporter. Study 3 evaluated the reproducibility of these responses after a period of one year. Study 4 utilised the methods of studies 1 and 2 in a case control study of patients with functional chest pain. Key Results Studies 1, 2 and 3 – Two pain phenotypes, or clusters, were found – cluster 1 (39%) had higher neuroticism scores, with higher sympathetic and hypothalamic pituitary adrenal axis tone at rest, and a predominant parasympathetic response to pain in the presence of the short allele of the serotonin transporter. Cluster 2 (61%) displayed the converse profile in the absence of the short allele. These responses were stable at an interval of one year. Study 4 – similar phenotypes were observed in patients with functional chest pain, although the Cluster 1 phenotype was overrepresented in patients in comparison to the controls (71% vs. 29%). Conclusions and Inferences This series of studies provides evidence for the existence of two reproducible human pain phenotypes in health, which have clinical salience in patients with functional chest pain. By phenotyping pain responses, subject homogeneity in future studies may be improved. Furthermore, such phenotyping techniques may open new therapeutic avenues by facilitating the selective targeting of nociceptive aberrancies, particularly in functional gastrointestinal disorders