Introduction
Fibromyalgia syndrome (FMS) is defined as widespread pain combined with tenderness at 11 or more of 18 specific 'tender points' [
1]. There is no consensus regarding the mechanisms underlying the set of symptoms reported by FMS sufferers. Additionally, several studies suggest heterogeneity in the diagnosis of FMS. For example, subgroup differences in biological variables such as positive antinuclear antibodies connected with features of connective tissue disease, interleukin 1β, interleukin-6, and tumor necrosis factor-alpha in skin (for example, see [
2‐
4]), depression and cytokine abnormalities (for example, see [
5,
6]), and responses to pharmacological interventions (for example, see [
7,
8]) have been reported. Subgroups based on psychosocial responses have also been demonstrated [
9]. Although abnormal responses to stress have been suggested to occur through a pathophysiological mechanism [
10], research examining the influence of stress in FMS has yielded inconsistent results.
The majority of published studies evaluated the responses of the autonomic nervous system to physical stressful situations. This approach was used to test stress-reactivity as a potential cause of the maintenance of FMS symptoms. Several studies reported increased skin conductance levels (SCLs) [
11], decreased heart rate (HR) variability [
12], blood pressure (BP), and skin temperature [
11] in response to physical stressors. These studies suggest an association between FMS and neurally mediated hypotension [
13].
Although several studies that investigated surface electromyographic (EMG) activity failed to find differences between FMS patients and healthy controls (HCs) [
14,
15], others reported lower than average muscle tension levels in FMS patients in contrast to HCs during isometric exercises (for example, see [
16,
17]), following injection of hypertonic saline, or in antagonistic muscles [
18,
19]. Our own study used psychological stressors (for example, mental and social stress), and measured a complex physiological pattern consisting of EMG levels, BP, HR and SCLs. FMS patients displayed reduced muscle tension and increased heart rate. In contrast, HCs showed a modest HR response to stress. Furthermore, as a group the FMS patients demonstrated significant variability in stress reactivity and thus do not appear to be a homogeneous group when it comes to stress reactivity [
20,
21].
These results support the suggestion of autonomic response specificity [
22,
23] as an explanation for the different response patterns observed in FMS. Furthermore, the results suggest that patients who have the same diagnosis may have different psychophysiological response patterns.
The primary aim of the present study was to identify psychophysiological characteristics of FMS patients by examining BP, HR, SCLs, and surface EMG levels during baseline (BL) and stress conditions [
23]. Based on the assumption of heterogeneity (for example, see [
3,
5,
8,
9]) and the studies by Qiao and colleagues. [
11], Graven-Nielson and colleagues. [
18], Sorensen and colleagues. [
19], and Sprott and colleagues. [
24], and our own study [
20], we predicted enhanced autonomic system (for example, SCL, HR, and BP) responses, and lowered muscle tension (for example, EMG levels) and different psychophysiological response patterns within the FMS sample.
Discussion
The results of this study demonstrate different physiological stress responses within FMS patients and between FMS patients and HC. The significant increase of BP, HR, and SCLs in the stress compared to the BL phase and the reduction in the REL phases indicates that stress and relaxation were induced, confirming the ecological validity of the stressors (compare to [
33]).
Consistent with other studies [
18,
34], in the FMS patients, muscle tension at the BL and the experimental phases were significantly lower compared to the HCs. Moreover, although the FMS patients rated the SC and MA tasks as stressful, their muscle tension levels did not display elevations comparable to the HCs. It appears that neither mental stress nor pain intensity influence muscle tension in FMS patients.
Studies with P magnetic resonance imaging have reliably identified several abnormalities in the muscles of patients with FMS, including low levels of phosphocreatine and ATP at rest, low phosphorylation potential and total oxidative capacity, and a reduced number and size of mitochondria [
23,
35]. Additionally, the slower degradation of acetylcholine [
36], which is involved in the production of corticosteroids and growth hormones [
10,
36], is an important regulator of muscle remodeling and performance [
37]. Taken together, the results of the present study and other physiological studies [
16‐
19,
32] suggest that FMS is characterized by decreased muscle activity connected with an inability to respond adaptively to stress and relaxation. The reason for the decreased muscle activity in FMS does not appear to be only the result of physical deconditioning; ultrastructural changes in the muscle also appear to be involved [
23,
31]. Further investigations are needed to examine the interactions between muscle and the endocrine [
37] and central nervous systems [
38].
The four psychophysiological stress response patterns identified differentiated among the FMS sample and the HCs. The HCs were included to examine the diagnosis specificity of each of the FMS patterns. If the HCs had not been included in the analyses, it would not have been possible to interpret the three psychophysiological FMS patterns as we would not have known whether any of these three clusters reflected a normal stress reaction. The inclusion of the HCs permitted us to demonstrate that the FMS patterns were all completely different when compared to the response pattern showed by the HCs.
These differences are important because autonomic variables may be involved in the development and maintenance of chronic disease [
21,
22]. Flor and colleagues [
39] found increased muscle reactivity in back pain patients following a psychological stress induction. Johannes and colleagues [
32] found greater BP reactivity in patients with hypertension compared to HCs. The largest percentage of the FMS sample (46.7%) in the present study showed hypotensive reactivity within a stress response pattern that is characterized by decreased cardiovascular, SCL, and EMG values. The significantly lower BP suggests that the influence of parasympathetic reactivity may be extended during stress situations. Based on the the endocrine influence on the autonomic nervous system [
40‐
42] and the central sensitization of FMS [
43], a parasympathetic response pattern seems to be connected with the enhanced adrenocorticotrophic hormone production described in FMS (for example, see [
10,
36]).
The second largest response pattern (37.8%) of FMS patients was exemplified by increased BP reactivity. Increased cardiovascular stress responses and decreased SCLs and EMG levels also characterized this response pattern. The increased cardiac response suggests a tendency for higher peripheral sympathetic tones under stress. This psychophysiological response pattern replicates the results reported by Martinez-Lavin [
44], who discussed FMS as a sympathetically maintained pain syndrome. Increased DBP appears to be connected to pain intensity (r = 0.32,
p < 0.05). It is comparable to the stress response observed in rheumatoid arthritis patients who also showed enhanced BP reactivity [
32]. Additional studies are necessary to confirm these results and to determine the mechanisms underlying these patterns.
The third largest response pattern of FMS (12.2%) was characterized by elevated SCL reactivity as sympathetic sudomotor reactivity and increased cardiovascular response as sympathetic vasomotor response as well as the FMS specific reduction in muscle tension. Patients with acute musculoskeletal injury also showed elevated sympathetic vaso- and sudomotor responses [
45]. These sympathetic response patterns suggest that there is an interaction between cutaneous and vasomotor sympathetic neurons in response to acute musculoskeletal injury or to chronic pain. This is reflected by increased afferent input from sensitized nociceptors and other sensory neurons, resulting in alterations in autonomic function [
45].
Johannes and colleagues [
32] also found sympathetic and parasympathetic response patterns in the comparison of patients with hypertension, rheumatoid arthritis, and systemic lupus erythematosus. As the sympathetic and parasympathetic response patterns are present in FMS as well, it may be that these response patterns are relatively independent of the specific disease entity.
Moreover, the patients were medication-free only one day before the study. It is known that antidepressant medication affects autonomic nervous system activity. However, a comparison of the physiological stress responses of the subgroups of patients with (n = 20) and without (n = 60) antidepressant medication did not yield significant effects (parasympathetic DBP, t(46) = 0.08, p = 0.94); sympathetic stress response t(37) = 1.15, p = 0.26). Antidepressant use was not associated with altered stress response. Further, the physiological response did not show significant differences between patients with and without antidepressant use.
Conclusion
The results of this study support the suggestion of heterogeneity of the mechanisms involved in FMS. They suggest further that differential treatment strategies matched to different patterns may be appropriate [
46,
47].
Although the overall sample size for the patient group appears reasonable, subdividing the total sample into four psychophysiological patterns produced relatively small groups. Thus, the interpretation of the results of the cluster analysis on the subgroups must be treated with caution. Research with larger samples is needed to replicate autonomic response specificity observed in the different psychosocial subgroups. Moreover, studies are needed to compare the psychophysiological reactivity in FMS with other chronic pain conditions to determine if the patterns observed are unique to FMS or are characteristic of chronic pain. Further, future research is needed to test endocrine predictors of stress reactivity in FMS to determine if the endocrine reaction is the cause or the consequence of FMS.
Competing interests
The authors declare that they have no competing interests.
Authors' contributions
KT: recruitment of the patients, organization and realization of the experimental design, statistical analyses, preparation of the manuscript. DCT: statistical analyses, preparation of the manuscript.