Subjects are at substantial increased odds of developing CWP if they display features of somatization, health-seeking behaviour and poor sleep. Psychosocial distress has a strong aetiological influence on CWP.

Objective. To test the hypothesis that abnormalities in the hypothalamic-pituitary-adrenal (HPA) stress-response system would act as an effect moderator between HPA function and the onset of chronic widespread pain (CWP).Methods. We conducted a population-based prospective cohort study. Current pain and psychosocial status were ascertained in 11,000 subjects. Of the 768 eligible subjects free of CWP but at future risk based on their psychosocial profile, 463 were randomly selected, and 267 (57.7%) consented to assessment of their HPA axis function. Diurnal function was measured by assessing levels of salivary cortisol in the morning (9:00 AM) and evening (10:00 PM). Serum cortisol levels were measured after an overnight low-dose (0.25 mg) dexamethasone suppression test and a potentially stressful clinical examination. All subjects were followed up 15 months later to identify cases of new-onset CWP.Results. A total of 241 subjects (94.9%) completed the followup study, and 28 (11. Conclusion. Among a group of psychologically at-risk subjects, dysfunction of the HPA axis helps to distinguish those who will and will not develop newonset CWP.6%Chronic widespread pain (CWP) affecting the musculoskeletal system, the principal symptom of fibromyalgia, is common, with a 1-month population prevalence of ϳ11% (1). It is associated with loss of function and considerable disability, may be associated with increased mortality rates (2), and is a major cause of health care utilization both in primary and secondary care settings. We have previously demonstrated in the prospective Altrincham Pain Study conducted in northwest England (3) that an increased risk of CWP onset is predicted from high levels of psychological distress, other somatic symptoms, and abnormal illness behavior. These factors are indicative of the process of somatization that can be defined as the tendency to express psychological distress as physical symptoms. These results confirmed for the first time that psychosocial factors preceded the onset of CWP, rather than just

To determine the relative contributions of psychological factors and sleep disturbance to reduced pain threshold we conducted a cross-sectional two-phase population-based study. A total of 424 subjects were recruited, stratified by pain and distress status. Subjects completed a postal questionnaire that asked about current pain and covered aspects of psychological status and sleep disturbance. Samples of subjects stratified by the extent of bodily pain they reported and psychological status were invited to participate in an examination of pain threshold. The association between psychological status, sleep disturbance and a low pain threshold was examined using ordinal regression. High levels of psychological distress (OR=1.6, 95% CI (1.02, 2.5)), disturbed sleep (OR=2.2, 95% CI (1.4, 3.5)) and high scores on the HAD depression scale (OR=2.1, 95% CI (1.3, 3.2)) were all associated with having a low pain threshold. In multivariate analysis disturbed sleep and depression remained independently associated with a low pain threshold. These relationships persisted after adjustment for pain status. This study had demonstrated that depression and poor sleep are associated with a reduced pain threshold.

BackgroundFibromyalgia syndrome (FM) is a chronic pain disorder characterized by widespread pain, sleep disturbance, fatigue and cognitive/affective symptoms. Functional imaging studies have revealed that FM and other chronic pain syndromes can affect resting brain activity. This study utilized electroencephalographic (EEG) recordings to investigate the relative power of ongoing oscillatory activity in the resting brain.MethodsA 64‐channel EEG was recorded at rest in 19 female FM patients and 18 healthy, age‐matched, control subjects. The Manual Tender Point Scale (MTPS) examination was performed to quantify tonic pain and tenderness on the day of testing along with measures of mood, arousal and fatigue. Oscillations in delta, theta, alpha, beta and gamma frequency bands were analysed using Standardised Low‐Resolution Brain Electromagnetic Tomography to evaluate sources of spectral activity throughout the whole brain.Results FM patients exhibited greater pain, tiredness and tension on the day of testing relative to healthy control participants and augmented theta activity in prefrontal and anterior cingulate cortices. No significant differences were seen in other frequency bands. Augmented frontal theta activity in FM patients significantly correlated with measures of tenderness and mean tiredness scores.ConclusionsThe findings indicate that alterations to resting‐state oscillatory activity may relate to ongoing tonic pain and fatigue in FM, and manifest in brain regions relevant for cognitive‐attentional aspects of pain processing and endogenous pain inhibition. Enhanced low‐frequency oscillations were previously seen in FM and other chronic pain syndromes, and may relate to pathophysiological mechanisms for ongoing pain such as thalamocortical dysrhythmia.SignificanceIncreased prefrontal theta activity may contribute to persistent pain in fibromyalgia or represent the outcome of prolonged symptoms. The findings point to the potential for therapeutic interventions aimed at normalizing neural oscillations, while further research utilizing quantitative analysis of resting EEG could benefit our understanding of fibromyalgia pathophysiology.

Fibromyalgia syndrome (FMS) patients show altered connectivity with the network maintaining ongoing resting brain activity, known as the default mode network (DMN). The connectivity patterns of DMN with the rest of the brain in FMS patients are poorly understood. This study employed seed-based functional connectivity analysis to investigate resting-state functional connectivity with DMN structures in FMS. Sixteen female FMS patients and 15 age-matched, healthy control subjects underwent T2-weighted resting-state MRI scanning and functional connectivity analyses using DMN network seed regions. FMS patients demonstrated alterations to connectivity between DMN structures and anterior midcingulate cortex, right parahippocampal gyrus, left superior parietal lobule and left inferior temporal gyrus. Correlation analysis showed that reduced functional connectivity between the DMN and the right parahippocampal gyrus was associated with longer duration of symptoms in FMS patients, whereas augmented connectivity between the anterior midcingulate and posterior cingulate cortices was associated with tenderness and depression scores. Our findings demonstrate alterations to functional connectivity between DMN regions and a variety of regions which are important for pain, cognitive and emotional processing in FMS patients, and which may contribute to the development or maintenance of chronic symptoms in FMS.

In clinic studies, altered hypothalamic-pituitary-adrenal (HPA) axis function has been associated with fibromyalgia, a syndrome characterised by chronic widespread body pain. These results may be explained by the associated high rates of psychological distress and somatisation. We address the hypothesis that the latter, rather than the pain, might explain the HPA results. A population study ascertained pain and psychological status in subjects aged 25 to 65 years. Random samples were selected from the following three groups: satisfying criteria for chronic widespread pain; free of chronic widespread pain but with strong evidence of somatisation ('at risk'); and a reference group. HPA axis function was assessed from measuring early morning and evening salivary cortisol levels, and serum cortisol after physical (pain pressure threshold exam) and chemical (overnight 0.25 mg dexamethasone suppression test) stressors. The relationship between HPA function with pain and the various psychosocial scales assessed was modelled using appropriate regression analyses, adjusted for age and gender. In all 131 persons with chronic widespread pain (participation rate 74%), 267 'at risk' (58%) and 56 controls (70%) were studied. Those in the chronic widespread pain and 'at risk' groups were, respectively, 3.1 (95% CI (1.3, 7.3)) and 1.8 (0.8, 4.0) times more likely to have a saliva cortisol score in the lowest third. None of the psychosocial factors measured were, however, associated with saliva cortisol scores. Further, those in the chronic widespread pain (1.9 (0.8, 4.7)) and 'at risk' (1.6 (0.7, 3.6)) groups were also more likely to have the highest serum cortisol scores. High post-stress serum cortisol was related to high levels of psychological distress (p = 0.05, 95% CI (0.02, 0.08)). After adjusting for levels of psychological distress, the association between chronic widespread pain and post-stress cortisol scores remained, albeit slightly attenuated. This is the first population study to demonstrate that those with established, and those psychologically at risk of, chronic widespread pain demonstrate abnormalities of HPA axis function, which are more marked in the former group. Although some aspects of the altered function are related to the psychosocial factors measured, we conclude that the occurrence of HPA abnormality in persons with chronic widespread pain is not fully explained by the accompanying psychological stress.

Background : Tender points are a general measure of distress both in the community and in clinic subjects. It has been suggested that multiple tender points should be regarded as the early stages of somatisation of distress. Similarly, recent evidence suggests that chronic widespread pain (CWP) is one manifestation of the somatisation of distress. Objective: Given that a high tender point count and CWP are clinical hallmarks of the fibromyalgia syndrome, it was hypothesised that in somatising subjects, a high tender point count or a low pain threshold would predict the development of CWP in the future. Methods: In this population-based prospective study, 245 adults aged 25-65 years, free of CWP, were identified on the basis of a detailed questionnaire on pain and a psychosocial questionnaire comprising the Somatic Symptom Checklist and the Illness Behaviour subscale of the Illness Attitude Scales. These subjects took part in a pain threshold examination with a Fischer pressure algometer. Tender point counts were computed by including all areas with a pain threshold ,4 kg/cm 2 . Individuals were followed up at 15 months, at which time 231 (93% of subjects still living at their baseline address) provided data on pain status, using the same instruments. Results: At follow-up, 26 (11%) subjects developed new CWP. Although subjects with a low baseline pain threshold were not at increased risk of developing symptoms, a high tender point count, adjusted for age, sex, baseline pain status and other confounding factors, predicted the development of new CWP. Conclusion: Subjects free of CWP are at an increased risk of its development if they have a high tender point count. However, a low-pressure pain threshold does not predict the onset of symptoms. Data from this population-based prospective study suggest that a low pain threshold in subjects with CWP is likely to be a secondary phenomenon as a result of pain or associated distress rather than the antecedent of symptoms.

Fibromyalgia syndrome is a chronic pain disorder characterised by widespread pain and tenderness in muscles and deep tissues. Current theories regarding the pathophysiological origins of fibromyalgia syndrome point towards central sensitisation and a decreased capacity of descending nociceptive controls. Morphological alterations to subcortical brain regions may contribute to such pathophysiological mechanisms, and to pain and other symptoms seen in fibromyalgia. Therefore, we evaluated geometric differences in subcortical structures in fibromyalgia patients relative to healthy people using a novel method of shape analysis. Sixteen female fibromyalgia patients and 15 age and sex matched, healthy control subjects underwent high-resolution T1-weighted magnetic resonance image scanning. Data was analysed using shape analysis of 15 subcortical regions and standard voxel-based morphometry analysis.Fibromyalgia syndrome patients, relative to healthy control participants, exhibited alterations to the shape of the left lateral aspect of the lower brainstem (medulla). The mean total volume of the brainstem was also found to be significantly reduced in the patient group compared to healthy control subjects, and this brainstem volume reduction in patient group significantly correlated with clinical manual tender point scale scores. Voxel-based morphometry analysis revealed that patients also demonstrated decreased local grey matter volumes in the brainstem (pons) and left precuneus, and increased grey matter volumes in bilateral primary somatosensory cortices.Results suggest that the volume reduction and associated geometric shape alterations seen in the brainstem of the patient group may contribute to sensitivity to pressure pain in fibromyalgia syndrome. This finding may be due to structure-related deficiencies in regions subserving descending nociceptive control.