| dc.description.abstract | Background
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. | |
