Background: Chronic widespread pain (CWP), the cardinal feature of the chronic pain disorder fibromyalgia, is prevalent in the general population. Psychosocial status has repeatedly been shown to be associated with the onset of CWP, yet it does not explain all new cases of the disorder and other risk factors have been implicated. Physically traumatic events, such as a road traffic accident (RTA) may "trigger" symptom onset. There is evidence from family and twin studies to suggest that there is a genetic component to CWP. Genetic association (GA) studies of fibromyalgia have been methodologically weak. The overall aim of this thesis was to examine the relative contribution of psychosocial factors, physically traumatic events, and specific genetic polymorphisms in the onset of CWP. Methods: The EPidemiology of FUNctional Disorders (EPIFUND) study, a prospective population-based study, was used. Subjects (aged 25-65 years) were recruited from three general practices in Northwest England. Information was collected via postal survey at three time points over four years. At baseline (T1), psychosocial status was assessed using a number of validated scales. Pain status was assessed at T1 and at both followups (carried out at 15 months (T2) and 47 months (T3ยป. CWP was classified using standard American College of Rheumatology criteria. Subjects free of CWP at T1 and with new onset CWP at T2 or T3 were identified. Regression techniques were used to investigate the relationships between psychosocial factors and traumatic events and CWP onset. At T3, subjects were also asked to provide a buccal swab sample from which DNA was extracted. A nested case-control study was conducted to investigate the GA of CWP (cases: CWP at ~ two time points; controls: free of pain at all three time points). Logistic regression models were used to analyse the relationship between genotype data and the presence of CWP. Results: 68% of eligible subjects participated at T1 (n=6791). At T2 and T3 the adjusted participation rate was 82% (n=3912) and 81% (n=2723), respectively. The onset rate of CWP was 10% (n=283) and 8% (n=145) at T2 and T3, respectively. High illness behaviour, somatic symptom, sleep problem, and depression scores were independent predictors of CWP onset at both 15 and 47 months of follow-up. Physically traumatic events did not independently predict the onset of CWP, although reporting a bone fracture, RTA, or childbirth, was univariately associated with CWP onset. The GA study (cases, n=153; controls, n=167) identified a number of associations between CWP and polymorphisms in genes on the hypothalamic-pituitary-adrenal axis and serotoninergic system. A number of these associations were moderated by psychosocial status (anxiety and depression). Conclusions: A psychosocial model for CWP onset that predicts the onset of CWP up to four years later has been established. Physically traumatic events do not appear to be important in the onset of CWP. Novel GAs with CWP have been identified. These findings highlight the multifactorial nature of CWP.
| Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:495737 |
| Date | January 2009 |
| Creators | Nicholl, Barbara Isabel |
| Publisher | University of Manchester |
| Source Sets | Ethos UK |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
Page generated in 0.0204 seconds