Chronic widespread pain in the community: the influence of psychological symptoms and mental disorder on healthcare seeking behavior

OBJECTIVE: To determine whether psychological symptoms and mental disorder are an intrinsic part of the chronic widespread pain syndrome or whether they have been observed in clinic attenders primarily because of their influence on the decision to seek a medical consultation. METHODS: A population survey of 1953 subjects was conducted in the Greater Manchester area of the United Kingdom. The survey included a postal questionnaire, and in a subgroup of respondents with high levels of distress, the presence of mental disorder was assessed by a semistructured standardized interview. Subjects with chronic widespread pain were classified according to whether they had sought a medical consultation for the reported pain ("consulters") or not ("nonconsulters"). RESULTS: In all, 252 subjects (13%) satisfied American College of Rheumatology criteria for chronic widespread pain, and of these 72% reported having consulted a general practitioner about this pain. There was a clear difference in levels of psychological distress, measured by the General Health Questionnaire (GHQ), between consulters, nonconsulters, and those with no pain. Consulters did not differ from nonconsulters in terms of levels of fatigue, social dysfunction, or number of somatic symptoms reported. Although consulters (among whom one in 4 had a mental disorder) were more likely to have a mental disorder than subjects without pain [OR = 4.9, 95% CI (2.6, 9.5)] the increase in risk comparing consulters to nonconsulters [OR = 2.1, 95% CI (0.7, 5.9)] and nonconsulters to subjects without pain [OR = 1.4, 95% CI (0.7, 2.6)] was not significant. CONCLUSION: The results suggest that psychological distress is associated with chronic widespread pain in addition to any effect on whether consultation is sought for symptoms. The finding that one-quarter of consulters to primary care with chronic widespread pain have a mental disorder should alert primary care physicians and rheumatologists to screen for mental disorder in this group.     

Analysis of heavy and light chain pairings indicates that receptor editing shapes the human antibody repertoire

In the bone marrow, diversity in the primary antibody repertoire is created by the combinatorial rearrangement of different gene segments and by the association of different heavy and light chains. During the secondary response in the germinal centres, antibodies are diversified by somatic mutation and possibly by further rearrangements, or "receptor editing". Here, we have analysed the pairings of heavy and light chain variable domains (VH and VL) in 365 human IgG+ B cells from peripheral blood, and established that these pairings are largely random. The repertoire is dominated by a limited number of pairings of segments and folds. Among these pairings we identified two identical mutated heavy chains in combination with two different mutated light chains (one kappa and one lambda). This shows that receptor editing occurs in the human periphery and that the same antibody lineage can be subjected to both receptor editing and somatic hypermutation. This suggests that receptor editing may be used together with somatic mutation for the affinity maturation of antibodies. We also propose that receptor editing has shaped variable gene segment use and the evolution of V gene families.     

A short episode of seizure activity protects from status epilepticus-induced neuronal damage in rat brain

Kainic acid (KA)-induced status epilepticus (SE) in adult rats results in extensive neuronal damage throughout the limbic system and the loss of selectively vulnerable neuronal populations, particularly CA3 neurons. We investigated the effects of a short episode of seizure activity on neuronal death elicited by a subsequent prolonged SE episode. A short episode of seizure activity was produced by sub-cutaneous (s.c.) injection of KA followed after 1 h by pentobarbital administration. Twenty-four hours later, KA was administered again, and animals were sacrificed 3 days later. Neuronal damage was estimated by visual analysis of neuronal density. Our results show that a short episode of seizure activity did not produce neuronal damage but almost completely protected vulnerable neurons from KA-induced neuronal damage. These results extend to epileptic tolerance the notion of tolerance previously described in the case of ischemia.     

NADPH diaphorase activity and nitric oxide synthase immunoreactivity in lordosis-relevant neurons of the ventromedial hypothalamus

The distribution of the enzymes NADPH diaphorase and nitric oxide synthase in the ventromedial nucleus of the hypothalamus of cycling and ovariectomized/estrogen-treated and control female rats was demonstrated using histochemical and immunocytochemical methods. Serial section analysis of vibratome sections through the entire ventromedial nucleus showed that NADPH diaphorase cellular staining was localized primarily in the ventrolateral subdivision. NADPH diaphorase staining was visible in both neuronal perikarya and processes. Light microscopic immunocytochemistry using affinity-purified polyclonal antibodies to brain nitric oxide synthase revealed a similar pattern of labelling within the ventromedial nucleus and within neurons of the ventrolateral subdivision of the ventromedial nucleus. Control experiments involved omitting the primary antibodies; no labelling was visible under these conditions. Some, but not all, neurons in the ventrolateral subdivision of the ventromedial nucleus contained both NADPH diaphorase and brain nitric oxide synthase as demonstrated by co-localization of these two enzymes in individual cells of this area. That NADPH diaphorase and brain nitric oxide synthase were found in estrogen-binding cells was shown by co-localization of NADPH diaphorase and estrogen receptor and brain nitric oxide synthase and estrogen receptor at the light and ultrastructural levels, respectively. Our studies suggest that brain nitric oxide synthase is present and may be subject to estrogenic influences in lordosis-relevant neurons in the ventrolateral subdivision of the ventromedial nucleus. The hypothalamus is a primary subcortical regulatory center controlling sympathetic function. Therefore, not only is nitric oxide likely to be important for reproductive behavior, but also for the regulation of responses to emotional stress and other autonomic functions.