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Rheumatology Advance Access originally published online on September 1, 2007
Rheumatology 2007 46(10):1587-1592; doi:10.1093/rheumatology/kem204
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© 2007 The Author(s)
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/2.0/uk/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Somaesthetic disturbances in fibromyalgia are exaggerated by sensory–motor conflict: implications for chronicity of the disease?

C. S. McCabe, H. Cohen and D. R. Blake

The Royal National Hospital for Rheumatic Diseases in conjunction with The School for Health, University of Bath, Bath BA1 1RL, UK.

Correspondence to: Dr C. S. McCabe, The Royal National Hospital for Rheumatic Diseases, Upper Borough Walls, Bath BA1 1RL, UK. E-mail: candy.mccabe{at}rnhrd-tr.swest.nhs.uk


   Abstract
Top
 Abstract
Introduction
 Patients and methods
 Results
 Discussion
 Acknowledgements
 References
 
Objectives. Conflict between sensory–motor central nervous processing generates somaesthetic disturbances, including pain, in healthy volunteers (HVs). Such conflict has been proposed as a potential cause of pain that occurs in the absence of injury or when the pain response is disproportionate to the injury. Fibromyalgia (FMS) exemplifies the former state. We hypothesized that the artificial generation of such conflict would exacerbate somaesthetic perceptions including pain in FMS greater than in HVs.

Methods. Twenty-nine adults with FMS took part in an established task that generates varied degrees of sensory–motor conflict during congruent/incongruent limb movements. A qualitative methodology recorded any changes in sensory experience. Data generated were compared with age and gender-matched HV data.

Results. Twenty-six subjects (89.7%) with FMS reported changes in sensory perception at some stage in the protocol in addition to, or worse than, baseline compared with 14 (48%) of HVs. All stages of the protocol generated a higher frequency of report in the FMS population than that of the maximum report in the HVs population. New perceptions included disorientation, pain, perceived changes in temperature, limb weight or body image.

Conclusions. Our findings support the hypothesis that motor–sensory conflict can exacerbate pain and sensory perceptions in those with FMS to a greater extent than in HVs.

KEY WORDS: Pain, fibromyalgia, sensory–motor conflict


   Introduction
Top
 Abstract
 Introduction
Patients and methods
 Results
 Discussion
 Acknowledgements
 References
 
The wide-spread chronic pain of fibromyalgia (FMS) is hard to understand due to the absence of overt clinical pathology. Indeed, the diagnosis is not accepted by some clinicians and the multiple symptoms reported considered to be a reflection of anxiety or attention-seeking behaviour. Nevertheless, it is one of the commonest conditions seen by rheumatologists with patients complaining of widespread pain, multiple tender points, stiffness, sleep disturbances and fatigue [1, 2]. In addition, this population have been found to have increased sensitivity to painful and non-painful thermal and mechanical stimuli as well as a perceptual amplification of sensations (hypervigilance) [3–7]. It has been proposed that these abnormalities in sensory processing may not only contribute to the onset of FMS but also maintain the condition [7]. Motor disturbances, such as slight tremor, a slowness in movement and restless leg syndrome, have also been described in those with FMS [8, 9] leading to comparisons being made to akinetic disorders such as Parkinson's disease [9]. Alongside these movement disorders are muscle weakness and loss of aerobic fitness [10–12].

Research to elucidate a mechanism has been intense and focused on both peripheral and central pain mechanisms (see Vierck, 2006 for review [13]). At a recent OMERACT (Outcomes Measure in Rheumatology) workshop, established to identify and prioritize outcome measures for FMS clinical trials, it was proposed that the symptoms of FMS arose from ‘central neuromodulatory disregulation’ evident by augmented pain processing [14, 15]. Biochemical studies have provided support for the central mechanism theorists with patients with FMS found to have nearly three times higher concentrations of substance P in their cerebrospinal fluid compared with healthy controls [16, 17]. In addition, lower levels of 3-methoxy-4-hydroxyphenethylene, which is the primary metabolite of norepinephrine, and reduced levels of serotonin are all thought to negatively influence both ascending and descending pain pathways resulting in the widespread allodynia and hyperalagesia commonly seen in FMS [15, 18, 19].

Melzack [20] would also attribute these symptoms to central neural mechanisms, but in the context of his neuromatrix theory of pain. He proposes that the symptoms of chronic pain syndromes such as FMS arise from the output patterns of the body-self neuromatrix, which activate ‘perceptual, homeostatic, and behavioural programmes’. The neural pattern is generated by the neuromatrix, which itself is genetically determined and influenced by sensory experiences. Thus, Melzack suggests that pain is a product of this pattern of activity rather than arising direct from sensory input. One factor that may influence Melzack's neuromatrix is a vulnerability to detecting or responding to sensory–motor conflict as described by our group [21]. We reported that a range of sensory disturbances, including pain, could be generated in 66% (n = 27) of a healthy volunteer (HV) population, when bilateral upper and lower limb movements are performed for 20 s, whilst viewing a mirror/whiteboard (optokinetic) device that created varied degrees of sensory–motor conflict during congruent/incongruent limb movements. Individual vulnerability to such sensory changes, as determined by report or no report of sensory changes at each stage of the protocol, showed the majority of the study population to fall within the mild to non-vulnerable categories with only six scoring moderate to high vulnerability. This pattern of distribution would be entirely in keeping with a genetically influenced vulnerability. The sensory disturbances described in the hidden limbs included discomfort to mild pain, perceived changes in temperature, weight and body schema and a feeling of peculiarity. These symptoms are similar to the widespread sensory disturbances described by those with FMS [2, 22] and with evidence of altered sensory and motor processing [3–7, 9], perhaps this population have an increased risk of maintaining the somaesthetic disturbances that arise from a motor–sensory conflict.

We therefore hypothesized that if the reported locomotor symptoms in patients with FMS were a presentation of a sensory–motor mismatch, then exacerbating this mismatch (via hiding a moving limb and/or distorting visual feedback of that limb), should exacerbate existing baseline symptoms and create new ones. We used an established qualitative method, identical to our previous study [21], to capture the wide spectrum of subjective experiences reported by those with FMS. This permitted direct comparison with our existing HV data.


   Patients and methods
Top
 Abstract
 Introduction
 Patients and methods
Results
 Discussion
 Acknowledgements
 References
 
Participants
Twenty-nine adult subjects diagnosed as suffering from FMS were recruited over a 1-year period from the out-patients’ clinics at the Royal National Hospital for Rheumatic Diseases, Bath, UK. A non-random, purposive sampling strategy was applied [23]. All patients had been diagnosed as having symptoms of FMS but no other concurrent condition, specifically no neurological illness that may have affected their proprioception and none had asymmetrical visible disfigurement on their upper or lower limbs. The individuals were provided with written and verbal information on the study. The subjects were informed that the purpose of their involvement was to collect data for a study exploring the effects of altered visual feedback on limb position sense in rheumatology conditions. The rationale provided was that people with FMS may have more difficulty accurately positioning their limbs than HVs. The subjects were informed that when movements were performed they might transiently be associated with ‘some strange sensations but these should not be painful’. This explanation met the criteria for informed consent as outlined by the approving ethics committee (Bath Local Ethics committee, UK) but was considered sufficiently vague not to induce a source of bias. Exactly the same terminology had been used for the HV control group and it should be noted that within the participant information sheet the primary emphasis was put on gaining information concerning limb position sense rather than any interest in potential sensory changes. Time was permitted for subjects to ask questions and written and verbal consent was gained prior to commencement of the assessment in accordance with the Declaration of Helsinki guidance [24]. Demographic details (including occupation) and a brief medical history (including hand dominance) were collected on all subjects to ensure that inclusion and exclusion criteria were satisfied.

Clinical method
In order to compare the data generated in this study with that of a previous cohort of HVs, precisely the same methodology was used as described fully in a previous publication [21]. Only a summary is included here. However, before recounting this it is important to note that the authors were very aware of the potential methodological problems involved in collecting subjective reports on somaesthetic changes from this study population. Those with FMS are already experiencing pain; they are a heterogeneous population in terms of the location and intensity of that pain. In addition, they are hypervigilant and, therefore, perhaps suggestible within an experimental setting. To try to address these possible confounders, control conditions, detailed subsequently, were included wherever possible to overcome these potential sources of bias.

Subjects performed a series of bilateral, upper and lower limb movements in a congruent and then incongruent manner, firstly, without the optokinetic device (baseline assessment) and then whilst attending to the whiteboard or mirror surfaces of the device (Fig. 1). The device was positioned at right-angles to the subject's body with one limb either side of it so that one limb was always concealed from view behind the device. The order of limb assessments was randomized and limb movements were performed for 20 s only at each stage of the protocol. On completion of limb movements the subjects were asked to position their visualized limb parallel to a marker on the board and move their hidden limb to the same felt position. This met the subjects’ expectations of a study to assess limb position sense as detailed in the participant information sheet. At the end of each stage subjects were asked a series of open questions: ‘How did that feel?’ followed by a further prompt ‘Were you aware of any changes in either limb?’ No specific direct enquiry was made about possible sensory changes to prevent leading the subjects and inducing a possible source of bias.


Figure 2
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  		FIG. 1. Experimental set up depicting congruent (A) and incongruent (B) whilst viewing the mirror or whiteboard surfaces of the optokinetic device.

 
Where painful perceptions were reported the subjects were asked to rate these on a verbal rating scale where, 0 = no pain and 10 = the worst possible pain. This scale is a modified Likert scale [25], which has been shown to reliably measure changes in pain [26]. A verbal rather than written scale was selected to minimize the interruptions in the procedure and thereby, aid the subject's concentration and recall skills.

Controls
For movement-induced-symptoms
The baseline assessment enabled the researchers to establish the sensory implications for the participants of normal repetitive, bilateral limb movement that is without visual perturbation or hiding a limb from view. Any symptoms reported in this stage were noted and if the same symptoms were reported in any of the intervention stages they were not included in data analysis; only additional or an exacerbation of pre-existing symptoms to baseline were included.

For fatigue
The effects of exercising both limbs for 20 s was captured in the baseline assessment but it was anticipated that over the course of five repetitions (one baseline, four intervention stages) fatigue would increase with a possible direct impact on increased symptom report. To address this, a rest period was included after each stage of the protocol and the next stage was only started once subjects felt their symptoms had returned to their baseline state. In addition, the order of limb assessments was randomized across the population. Finally, if fatigue was playing a role in symptom report, we would anticipate that this would be a bilateral limb effect as both limbs performed the same number of repetitions. Our previous study with HVs had demonstrated a unilateral limb affect, predominantly in the hidden limb and, therefore, a similar pattern was anticipated in the FMS population.

For hypervigilance and potential suggestibility
In order to minimize symptom report arising from internal effects, such as increased attention by the participant to anomalous sensations in their limbs, and external affects, such as increased attention from the researcher, the focus of the study was portrayed as an exploration into limb position sense in FMS. This was explicitly described in the information sheet and reinforced by the protocol requirement for subjects’ to align their limbs in parallel with a marker at the end of each stage of the protocol. The aim was for subjects’ attention to be primarily focused on how well they could align a hidden and visualized limb so that any changes in sensation were of secondary interest. The baseline stage captured any sensory changes arising from participants attending to their moving limbs and also helped to familiarize subjects with the movements required, thereby reducing anxiety during the intervention stages.

Data analysis and management
Qualitative data generated from the subjects’ responses to the open questions were tabulated on MS-Excel and analysed using content analysis [27, 28]. Subjects were each allocated a unique code and the responses to the open questions were typed against the individual's code under the relevant stage in the protocol. Colour coding was used to indicate categories and sub categories within emergent themes. The frequency of report of a particular perception was totalled for each stage of the protocol. Only changes from baseline were included within data analysis for the whiteboard or mirror stages. Quantitative data relating to the verbal rating scales for sensation severity were stored and analysed on SPSS. These were tabulated against each individual's code for the relevant stage in the protocol. This study was not designed to consider quantitative differences between groups, but qualitative variances. Therefore, it was under powered for statistical analysis and would not have provided reliable quantitative results if this type of data analysis had been undertaken.

Data were compared with age - (≤ 10yrs) and gender-matched data from a previous cohort of HVs (n = 29) as described in a previous publication [21].


   Results
Top
 Abstract
 Introduction
 Patients and methods
 Results
Discussion
 Acknowledgements
 References
 
Fibromyalgia population
Twenty-nine subjects (one male) with FMS were recruited (comorbidities: Raynauds phenomenon = 1, possible psoriatic arthritis = 1) aged from 27 to 74 yrs (mean 47.9 yr, S.D. 11.1) with the majority right hand dominant (n = 25). Twenty-six subjects reported sensory changes at some stage in the protocol, in addition to, or worse than, baseline; only three describing no effect. The frequency and range of symptoms reported varied across the study population with some appearing more susceptible to the triggering of these symptoms than others. Table 1 shows the FMS study population categorized into four groups of varying levels of vulnerability to sensory disturbances. This has been based upon subjects’ frequency of symptom reports. Vulnerability to the generation of symptoms in FMS population was: high, n = 16; moderate, n = 3; mild, n = 4; minimal, n = 3.


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  		TABLE 1. Details of FMS subject's characteristics showing type of protocol-induced symptoms, in addition to those at baseline in relation to stage in the protocol, limb affected and individual vulnerability (data on high to mild vulnerability subjects only)

 
Healthy volunteer population
The results of the 29 age- and gender-matched HVs (one male) aged from 23 to 65 yrs (mean 43.4 yrs, S.D. 10.5) with the majority right hand dominant (n = 26) were that 14 subjects reported sensory changes at some stage in the protocol; with 15 describing no effect (one male). Vulnerability (Graph 1) to the generation of symptoms in this comparison group was: high, n = 2; moderate, n = 2; mild, n = 5; minimal, n = 5.


Figure 1
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  		GRAPH 1. Number of individuals ranked none—high vulnerability in subjects with fibromyalgia (FMS) and healthy volunteers (HVs).

 
Data comparison between FMS and HV groups
Fibromyalgia subjects reported the same range of symptoms as those previously described by HV. That is: discomfort, changes in temperature and/or weight, perceived additional or lost limbs and disorientation (see McCabe et al. 2005 [21] for detailed descriptions). For those who reported a new or increased pain this occurred at any stage of the protocol and was described as ‘stiff ’, ‘achy’, ‘crampy’, ‘hurting’, ‘burning’ and ‘deeply painful’. Pain was quantified from 2/10 to 10/10 on a verbal rating scale with an average of 5/10 for each stage of the protocol (HV ≤ 2/10). These types of pain were very familiar to the FMS population and they described them in terms of feeling that they had a ‘flare’ of their condition.

The only additional sensations reported by the FMS cohort that were not described in the HV cohort were those of phantom swelling and tiredness. Phantom swelling has been previously defined as the perception of swelling of a limb, or of part of a limb, when the subject and clinician are both aware that on visualization of that area no swelling exists [29]. Bilateral phantom swelling of the hands was reported by eight FMS subjects at baseline and in one of those subjects on incongruent mirror visual feedback. This latter report was not a simultaneous sensation in both hands, but a consecutive report of the perception of excessive swelling in either the left or right hand, when it was hidden from view during the different stages of the protocol. All altered sensations faded rapidly after limb movement had ceased and the hidden limb could be directly visualized by the subject.

Altered, or exacerbated, sensations were predominantly described in the hidden limb, with a distal to proximal spread, though some subjects with FMS (n = 8) also reported changes in pain and weight in the visualized limb. This was described in all stages of the protocol (whiteboard congruent movement, n = 1; incongruent movement, n = 3; mirror congruent movement, n = 2; incongruent movement, n = 2). There were no reports of increased pain in other body regions or specific FMS tender points, though it should be noted that subjects were not palpated.

Frequency of report (Table 2)
Sensory changes from baseline were reported by the FMS and HV populations through all phases of the protocol: whiteboard (congruent movement FMS, n = 18; HV, n = 5; incongruent movement FMS, n = 22; HV, n = 2) and mirror (congruent movement FMS, n = 22; HV, n = 10; incongruent movement FMS, n = 20; HV, n = 17). The HVs reported increased symptoms when viewing the mirror with a maximum report while performing incongruent movements: the time of greatest sensory–motor conflict. No such pattern was seen in the FMS population. Each stage of the protocol generated a similar frequency of report, with whiteboard congruent movement the lowest. However, all stages of the protocol generated a higher frequency of report in the FMS population than that of the maximum report in the HV population.


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  		TABLE 2. Details of the incidence of symptoms reported by subjects with fibromyalgia (FMS) and healthy volunteers (HVs) at each stage of the protocol in relation to the total study populations

 

   Discussion
Top
 Abstract
 Introduction
 Patients and methods
 Results
 Discussion
Acknowledgements
 References
 
We have examined the impact of transient sensory/motor conflict in FMS population. Our findings suggest that visually mediated changes between motor output and predicted somatosensory feedback (via hiding a moving limb and/or distorting visual feedback of that limb) are sufficient to produce the additional somaesthetic disturbances, and exacerbation of pre-existing symptoms, seen in our study population. This happens in a similar manner in HV but importantly less frequently and to a lesser extent. In addition, the maximum report of somaesthetic disturbances in the HV population was during incongruent mirror visual feedback, the time of greatest sensory–motor conflict. This was not seen in the FMS population; there was no difference in frequency of report across the intervention stages though it was greater than baseline, and at every stage of the protocol compared with the HV population. This would appear to support our hypothesis that a pre-existing motor/sensory conflict is present in the FMS population, which, when exacerbated via manipulation of visual feedback, baseline symptoms are exacerbated and new ones generated. This proposal would be supported by a number of sources.

Firstly, the range of symptoms reported by both cohorts of research subjects are remarkably similar to those routinely described by those with FMS; pain, temperature variance, altered body perception and a heaviness in the limbs [2, 22]. The FMS subjects related to these symptoms, particularly the types of pain, as being very similar to those they experience in a flare of their condition. Second, the FMS population demonstrated a greater vulnerability to the generation of these symptoms than the HVs (FMS 89.7% compared with HV 48%). It has been demonstrated that an individual only becomes aware of a deviation between motor intention and expected sensory feedback when the magnitude of discordance exceeds a certain threshold and that this level of threshold varies between individuals [30, 31]. We would propose that the chronicity of somaesthetic disturbances seen in FMS arise from having a reduced threshold to sensory–motor discrepancies as compared with HVs. Their known hypervigilance may contribute to such a state and be further exacerbated by the motor disturbances, muscle weakness and increased sensitivity to a range of painful and non-painful stimuli that have been reported in this population [3–9]. This could also explain why the relatively minor intervention of simply hiding a limb from view is sufficient to alert the individual to an anomaly within the motor control system. We have previously suggested that when such an alert is triggered somaesthetic disturbances are generated to warn the individual of an abnormality in information processing so that remedial action can be taken [21]. Where the threat is persistent or deemed as great, then pain will ultimately be experienced. If in those with FMS, the magnitude of discordance required to trigger this cascade of events is relatively low it may explain why there was such little variance between the frequencies of report across the phases of the protocol, particularly that no additional exacerbation of symptoms was seen during incongruent mirror visual feedback, the time of greatest sensory–motor discrepancy. This contrasts with the HV population, where the majority required the larger perturbation of distorted visual input, via incongruent movements, whilst viewing a mirror to generate anomalous symptoms.

Finally, FMS is a multidimensional syndrome with features in addition to those described earlier including cognitive disturbances, fatigue, irritable bowel syndrome, tension and migraine headaches [32]. Many of these features are seen with chronic stress. If, as has been proposed [21], the motor control system generates somaesthetic disturbances to act as an alert mechanism to warn the body that there is a discrepancy in two of its major systems, motor and sensory, then it would be logical to assume that this would also activate the autonomic nervous system. Autonomic dysfunction is frequent in FMS with sympathetic hyperactivity and hyporeactivity having been described [33–36]. The explanation for this apparent inconsistency of hyperactivity co-existing with hyporeactivity has been attributed to the chronicity of the stress process in FMS, which results in receptor desensitization and down-regulation [37, 38]. Quite which is cause and effect in this scenario of a motor control alert mechanism and altered sympathetic activity is impossible to determine from our study findings but these feedback systems may in themselves maintain the wide range of somaesthetic complaints seen in FMS.

It is of interest that therapies aimed at improving physical function have been demonstrated to give significant improvement, at least in the short term, for FMS-related pain [39–42]. Perhaps pre-existing sensory–motor incongruence is reduced with the subsequent heightened proprioception and it is via this route that any analgesic benefit is derived. A similar mechanism may be responsible for the anecdotal reports of reduced pain with massage, and it should be noted that the three subjects with FMS who reported no additional or altered somaesthetic disturbances during the study protocol, were at the time all attending an out-patient coping skills programme. This programme included education on pacing activities, promoted regular exercise and gave guidance on what those exercises should be. Further study of prospective data are required to establish if there is a direct relationship between this educational programme and reduced vulnerability to sensory–motor discrepancy, but improved sensory input may be beneficial in this population.

It could be argued that our findings in the FMS population simply arise from the exertion of bilateral limb movements exacerbating pre-existing symptoms, particularly as these patients frequently report fatigue. This seems improbable. The baseline assessment of looking at the moving limbs without the optokinetic device did not produce the same symptoms in regard to quantity of report or character, and when new symptoms did occur during the mirror/whiteboard stages these were almost immediately lost (within 1–2 min) once the optokinetic device was removed and normal visual input was restored. In addition, the majority of symptoms were reported only in the hidden limb and, as both limbs were moving throughout the protocol it seems unlikely that fatigue would only affect one limb at a time, or indeed move over to the hidden limb as the protocol progressed.

In conclusion, we would propose that sensory–motor conflict may perpetuate some of the somaesthetic disturbances reported in FMS. This may occur either because an individual has an innate vulnerability to sensory–motor disturbances and/or they develop a heightened awareness, or reduced threshold, to the daily minor sensory changes that are generated when predicted sensory feedback does not match actual. External or internal factors, such as physical or emotional stressors, may maintain either scenario. These normal sensory changes will naturally fluctuate in frequency and character but they are reported as abnormal symptoms by the hypervigilant individual. Autonomic systems are alerted and the increased stress response perpetuates the cycle.


   Acknowledgements
Top
 Abstract
 Introduction
 Patients and methods
 Results
 Discussion
 Acknowledgements
References
 
We would like to thank and acknowledge all our research participants who gave up their time so freely and Dr. Tulin Bodamyali for her significant contribution in data collection. This study was funded by the Gwen Bush Foundation. D. R. Blake holds an endowed Chair—‘The Glaxo Wellcome Chair in Locomotor Sciences’. An Arthritis Research Campaign ICAC award supports the Royal National Hospital for Rheumatic Diseases, Bath, UK.

Formula

The authors have declared no conflicts of interest.


   References
Top
 Abstract
 Introduction
 Patients and methods
 Results
 Discussion
 Acknowledgements
 References
 

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Submitted 27 April 2007; revised version accepted 29 June 2007.
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