A two-component model of hair cortisol concentration in fibromyalgia: Independent effects of pain chronicity and severity.

BACKGROUND: Fibromyalgia (FM) is a chronic pain disorder of unknown aetiopathogenesis, in which the role of activity of the hypothalamic-pituitary-adrenal (HPA) axis is not clearly established. METHODS: This study analysed the modulatory effects of disease chronicity and severity on cortisol levels. Hair cortisol concentrations (HCC) and clinical evaluation data (pain severity, impact of FM on daily activities, depression, anxiety, fatigue and insomnia) were collected from 47 female patients with FM and 36 healthy women (HW). RESULTS: The results showed that disease chronicity, with a negative effect, and symptom severity, with a positive effect, were independent predictors of HCC. Patients with a shorter disease duration had higher HCC than patients with a longer disease duration and healthy participants. Furthermore, patients with greater symptom severity had higher HCC than those patients with lower clinical severity and healthy participants. While disease chronicity in FM was associated with a decrease in HCC, clinical severity increased HCC. CONCLUSIONS: These results support the existence of a dysfunction in the regulation of the HPA axis in FM and its possible contribution to chronic pain development. SIGNIFICANCE: This is the first study to assess hair cortisol concentrations in a specific sample of patients with fibromyalgia (FM). This method is especially useful for the assessment of long-term regular cortisol excretion. Results showed a two-component model for explaining cortisol levels: disease chronicity, with a negative effect, and symptom severity, with a positive effect. This suggests that severe pain/stress evokes higher cortisol levels at earlier stages of FM, while in the longer term a decrease in cortisol levels was observed.

Cognitive impairment in fibromyalgia syndrome: the impact of cardiovascular regulation, pain, emotional disorders and medication.

This study investigated cognitive performance in fibromyalgia syndrome (FMS) and its association with cardiovascular and clinical parameters. Thirty-five patients with FMS and 29 matched healthy controls completed a neuropsychological test measuring attention and arithmetic processing. As possible factors underlying the expected cognitive impairment, clinical pain intensity, co-morbid depression and anxiety disorders, sleep complaints, medication use, as well as blood pressure parameters were investigated. The patients' test performance was substantially reduced, particularly in terms of lower speed of cognitive processing and restricted improvement of performance in the course of the task. While the extent of depression, anxiety, fatigue and sleep complaints was unrelated to test performance, better performance was observed in patients showing lower pain ratings and those using opiate medication. The data corroborate the presence of substantial cognitive impairment in FMS. While the experience of chronic pain is crucial in mediating the deficits, co-morbid depression, anxiety, fatigue and sleep complaints play only a subordinate role. In the control group, but not in the patients, blood pressure was inversely associated with mental performance. This finding is in line with the well known cognitive impairment in hypertension. The lack of this association in FMS confirms previous research showing aberrances in the interaction between blood pressure and central nervous function in the affected patients.

Haemodialysis course is associated to changes in pain threshold and in the relations between arterial pressure and pain.

ANTECEDENTS: Arterial pressure is negatively associated to pain perception. OBJECTIVES: In this study, pain and the relations between arterial pressure and pain threshold were compared at the beginning and end of the haemodialysis. METHODS: 14 patients with chronic renal disease participated in the study. Pain thresholds were evaluated with pressure algometry bilaterally at two tender points: the second rib and the knee. Arterial pressure and pain thresholds were assessed twice: 1) 15 min alter dialysis onset and 2) 30 min before dialysis ended. RESULTS: Arterial pressure remains unchanged through the dialysis. The course of dialysis was associated to a decrease in pain threshold in the second left rib and left and right knees. At the beginning of dialysis arterial pressure were uncorrelated with pain, while at the end of the dialysis both systolic and diastolic arterial pressure were strongly associated to pain thresholds (rs between 0.552 and 0.806): increased arterial pressure was associated to lower pain in terms of increased threshold. CONCLUSIONS: Haemodialysis is associated to changes in pain sensitivity and in the relationships between arterial pressure and pain, suggesting a modification in the ascending pain inhibition system arising from the cardiovascular system. Possible explanations of this effect include the changes produced by haemodialysis in cognitive-perceptive functions, in autonomic cardiovascular regulation, and in the habituation of stress-related variables.

Relationship between baroreceptor cardiac reflex sensitivity and pain experience in normotensive individuals.

In the present study, the relationship between cardiac baroreceptor function and the perception of acute pain was investigated in 60 normotensive subjects. Baroreceptor reflex sensitivity was determined using the sequence method based on continuous blood pressure recordings. A cold pressor test was used for pain induction. Visual analogue scales and a questionnaire were applied in order to quantify sensory and affective pain experience. Moderated multiple regression analysis revealed an inverse relationship between baroreceptor reflex sensitivity assessed during painful stimulation and the intensity of experienced pain. This relationship was moderated by resting blood pressure, with decreasing blood pressure being accompanied by a decrease in the magnitude of the association. Furthermore, resting blood pressure was inversely related to pain intensity. The inverse association between baroreceptor reflex sensitivity and pain experience is discussed as reflecting the well-established pain-inhibiting effect of baroreceptor activity. The finding that this relationship was less pronounced in the case of lower blood pressure suggests that baroreceptor-mediated pain attenuation is reduced in this population.

A biofeedback system of baroreceptor cardiac reflex sensitivity.

The evidence presently available suggests that the parasympathetic nervous system and sympathetic-parasympathetic interactions could play a role in the pathophysiology of cardiovascular disorders and, specifically, in hypertension. A loss of sensitivity of the baroreceptor reflex is one of the fundamental mechanisms underlying the deficits found in parasympathetic cardiac control. The baroreceptor reflex is a basic mechanism for the regulation of blood pressure, a powerful source of vagal afferent input to the central nervous system, and one of the most important physiological mechanisms affecting efferent cardiac vagal activity. This paper describes a computerized system for the on-line analysis of the baroreceptor cardiac reflex function using the noninvasive spontaneous sequence method in the time domain. The system provides feedback of the baroreceptor reflex sensitivity (the change in heart period per unit change in systolic blood pressure) differentially both when the systolic blood pressure is increasing and when it is decreasing. The accuracy of the described system has been tested against the conventional off-line procedure. None of the parameters supplied by the analysis show a significant difference between the on-line and off-line methods. These results confirm the accuracy of the on-line system to analyze baroreceptor cardiac reflex function.

The continuing problem of incorrect heart rate estimation in psychophysiological studies: an off-line solution for cardiotachometer users.

A wide variety of procedures are commonly used to record and estimate heart rate in psychophysiological studies. We analyze biases inherent in some estimates of mean heart rate based on cardiotachometers. Two types of errors are described, the time lag error and the incorrect weighted averaging error. These lead to an overestimation of the true heart rate, even when the analysis is based on digitized samples. Digitized samples provide a series of heart rate values per beat which correspond to the prior interbeat interval but during a time which does not correspond to the prior interval, but to the current one. A simple and practical solution, which eliminates both types of errors, is presented: an algorithm that corrects off-line the cardiotachometer data, reproducing the heart rate value with a length of time equal to the length of its own R R interval. Several comparisons between the corrected and uncorrected data are made to illustrate the magnitude of the error.

Physiological significance of the defense response to intense auditory stimulation: a pharmacological blockade study.

This paper examines through pharmacological blockade some questions related to the physiological significance of the defense response to intense auditory stimulation. Nine subjects received intravenous metoprolol (10-15 mg i.v.), intravenous atropine (0.03 mg/kg i.v.), or a saline solution as placebo condition before undertaking a test of the defense response to a distorted sound of 400 Hz frequency, 109 dB intensity, 0.5 sec duration and virtually instantaneous risetime. Dependent variables were continuous (beat-to-beat) heart rate, stroke volume and blood pressure. The results suggest: (1) a vagal origen of the first acceleration and first deceleration and a sympathetic-parasympathetic interaction during the second acceleration and second deceleration of the heart rate response; (2) a blood pressure response pattern characterized by an increase during the first heart rate deceleration (4-11 sec), a posterior decrease coinciding with the second heart rate acceleration (from 12 to 37 sec), and a lighter increase during the second heart rate deceleration (from 38 to 63 sec); and (3) an implication of the baroreceptor reflex, including a baroreceptor mediated inhibition of the parasympathetic cardiac activity during the second accelerative component of the cardiac response.

Respiratory influences on the cardiac defense response.

An investigation to examine the relationships between breathing activity and the cardiac defense response (CDR) to intense auditory stimulation is reported. 42 subjects (20 men and 22 women) underwent a physiological reaction test consisting of three trials of a distorted 400 Hz noise of 100 dB, 0.5-s duration and instantaneous risetime presented either during inspiration or expiration. The respiratory response was characterized by a specific increase in breathing amplitude both in the respiratory cycle in which the stimulus was presented and in the 80 s following stimulus onset. Significant habituation effects were observed. Manipulation of the respiratory phase did not produce any major effect on the respiratory or cardiac response. The only significant finding was observed in the inspiratory period of the cycle in which the stimulus was presented, which was longer when the stimulus was presented in expiration and shorter when it was presented in inspiration. The evocation of the cardiac defense response was dependent on the observed increase in breathing amplitude. Gender differences were also observed in the respiratory response, differences which were further increased when the CDR was elicited. These results are discussed in the context of centrally versus peripherally-mediated mechanisms and startle versus defense reflexes.

Respiratory sinus arrhythmia as an index of parasympathetic cardiac control during the cardiac defense response.

The respiratory sinus arrhythmia (RSA) is being used by psychophysiologists as an index of parasympathetic cardiac control mainly in tasks within a tonic response paradigm. In procedures which engender phasic responses the belief exists that the RSA could be contaminated by slower nonrhythmic trends in the data. In the present paper two experiments are reported. The first experiment valuates, through beta-adrenergic blocking, the validity of the RSA as an index of phasic changes in parasympathetic cardiac control during phasic changes in sympathetic activation: the cardiac defense response (CDR) to intense auditory stimulation. The second experiment examines the RSA response pattern associated with the CDR. The results of the first experiment, that the RSA response pattern is not significantly influenced by the beta-adrenergic block, suggest that RSA may index phasic changes in parasympathetic cardiac control during phasic response procedures such as those which elicit the CDR. The results of the second study indicate that the CDR is associated with a pattern of changes in RSA made up of four components--reduction, increase, reduction and increase--which run parallel, but in opposite direction, to the heart rate changes. The results of both studies are consistent with a parasympathetic mediation of the first two components of the CDR and a sympathetic-parasympathetic interactive mediation of the last two components.

Self-regulation of respiratory sinus arrhythmia.

Respiratory sinus arrhythmia (RSA)--the peak-to-peak variations in heart rate caused by respiration--can be used as a noninvasive measure of parasympathetic cardiac control. In the present study four strategies to increase RSA amplitude are investigated: (1) biofeedback of RSA amplitude, (2) biofeedback of RSA amplitude plus respiratory instructions, (3) respiratory biofeedback, and (4) respiratory instructions only. All four procedures produce a significant increase of RSA amplitude from the first physiological control trial compared to baseline. This increase is faster for the groups that received respiratory biofeedback and respiratory instructions only than for the two groups that received biofeedback of RSA amplitude, the increases being equivalent for the four groups in the third session. All subjects of the group that received biofeedback of RSA amplitude only reported respiratory strategies in order to achieve the increase in RSA. Possible clinical implications of these results for parasympathetic cardiac control and cardiovascular disorders are discussed.