Morning cortisol and fasting glucose are elevated in women with chronic widespread pain independent of comorbid restless legs syndrome

Background and aims: Chronic widespread pain (CWP) is associated with poor quality of sleep, but the detailed underlying mechanisms are still not fully understood. In this study we investigated the influence of CWP on morning cortisol and fasting glucose concentrations as well as sleep disordered breathing. Methods: In this case-control study, subjects with CWP (n=31) and a control group without CWP (n=23) were randomly selected from a population-based cohort of women. Current pain intensity, sleep quality, excessive daytime sleepiness [Epworth sleepiness scale (ESS)], psychiatric comorbidity and occurrence of restless legs syndrome (RLS) were assessed. Overnight polygraphy was applied to quantify sleep apnoea, airflow limitation and attenuations of finger pulse wave amplitude (>50%) as a surrogate marker for increased skin sympathetic activity. Morning cortisol and fasting glucose concentrations were determined. Generalised linear models were used for multivariate analyses. Results: CWP was associated with higher cortisol (464±141 vs. 366±111 nmol/L, p=0.011) and fasting glucose (6.0±0.8 vs. 5.4±0.7 mmol/L, p=0.007) compared with controls. The significance remained after adjustment for age, body mass index, RLS and anxiety status (β=122±47 nmol/L and 0.89±0.28 mmol/L, p=0.009 and 0.001, respectively). The duration of flow limitation in sleep was longer (35±22 vs. 21±34 min, p=0.022), and pulse wave attenuation was more frequent (11±8 vs. 6±2 events/h, p=0.048) in CWP subjects compared with controls. RLS was associated with higher ESS independent of CWP (β=3.1±1.3, p=0.018). Conclusions: Elevated morning cortisol, impaired fasting glucose concentration and increased skin sympathetic activity during sleep suggested an activated adrenal medullary system in subjects with CWP, which was not influenced by comorbid RLS. Implications: CWP is associated with activated stress markers that may deteriorate sleep.

Autonomic Physiology

The autonomic nervous system consists of three divisions: the sympathetic (thoracolumbar), parasympathetic (craniosacral), and enteric nervous systems. The sympathetic and parasympathetic autonomic outflows involve a two-neuron pathway with a synapse in an autonomic ganglion. Preganglionic sympathetic neurons are organized into various functional units that control specific targets and include skin vasomotor, muscle vasomotor, visceromotor, pilomotor, and sudomotor units. Microneurographic techniques allow recording of postganglionic sympathetic nerve activity in humans. Skin sympathetic activity is a mixture of sudomotor and vasoconstrictor impulses and is regulated mainly by environmental temperature and emotional influences. Muscle sympathetic activity is composed of vasoconstrictor impulses that are strongly modulated by arterial baroreceptors. Heart rate is controlled by vagal parasympathetic and thoracic sympathetic inputs. Vagal influence on the heart rate is strongly modulated by respiration; it is more marked during expiration and is absent during inspiration. This is the basis for the so-called respiratory sinus arrhythmia, which is an important index of vagal innervation of the heart. Power spectral analysis of heart rate fluctuations allows noninvasive assessment of beat-to-beat modulation of neuronal activity affecting the heart. Arterial baroreflex, cardiopulmonary reflexes, venoarteriolar reflex, and ergoreflexes control sympathetic and parasympathetic influences on cardiovascular effectors. The main regulatory mechanism that prevents orthostatic hypotension is reflex arterial vasoconstriction in the splanchnic, renal, and muscular beds triggered by a decrease in transmural pressure at the level of carotid sinus baroreceptors.