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Influence of Social Support and Emotional Context on. Pain Processing and Magnetic Brain Responses in Fibromyalgia. Pedro Montoya,1 Wolfgang Larbig,2 ...
ARTHRITIS & RHEUMATISM Vol. 50, No. 12, December 2004, pp 4035–4044 DOI 10.1002/art.20660 © 2004, American College of Rheumatology

Influence of Social Support and Emotional Context on Pain Processing and Magnetic Brain Responses in Fibromyalgia Pedro Montoya,1 Wolfgang Larbig,2 Christoph Braun,2 Hubert Preissl,2 and Niels Birbaumer3 painful tender point in the presence of their significant others as compared with the ratings when the patients were alone. Brain activity elicited by elbow stimulation was also significantly reduced in FM patients when a significant other was present as compared with the activity when the patient was alone. These effects were not observed in the migraine patients. Conclusion. When the significant other was present, FM patients reported less pain and thermal pain sensitivity and showed diminished brain activity elicited upon tactile stimulation of a tender point compared with these levels when the patients were alone. These findings are consistent with the hypothesis that social support through the presence of a significant other can influence pain processing at the subjective– behavioral level as well as the central nervous system level.

Objective. To examine the effects of social support provided by the presence of patient’s significant other on pain ratings, pain thresholds, and brain activity associated with tactile stimulation in 18 fibromyalgia (FM) patients and 18 migraine patients (controls), and to assess the influence of emotional context on thermal pain perception and processing of non–pain-related information. Methods. Thermal pain thresholds and somatosensory brain magnetic responses elicited by tactile stimulation at the elbow (a painful tender point in the FM group) and at the finger (nonpainful site) were evaluated under 2 experimental conditions of social support: patient alone and patient’s significant other present. Brain activity was recorded using a 151channel whole-head magnetoencephalography system. Additionally, the emotional context during presentation of tactile stimuli was manipulated by presenting aversive, pain-related pictures and neutral pictures and asking the patients to imagine that they were experiencing the situations depicted. Results. Thermal pain thresholds indicated greater sensitivity in FM patients than in migraine patients, as well as enhanced sensitivity at the elbow than at the fingers. Specifically, in FM patients, there were significant reductions in pain sensitivity and subjective pain ratings when patients were stimulated at the

The diagnosis of fibromyalgia (FM) as defined by the American College of Rheumatology (ACR) (1) includes such criteria as chronic widespread musculoskeletal pain, morning stiffness, insomnia, fatigue, cognitive problems (2), and often, depression and headache. In addition to these complaints, FM patients typically have a minimum of 11 tender points (of a total of 18 specific tender points), which are characterized by decreased pressure–pain thresholds that result in hyperalgesia and/or allodynia. Little is known about the influence of psychosocial and affective mood on processing of pain-related and non–pain-related information among FM patients. Psychosocial factors, such as perceived social support, have been suggested to influence pain perception in patients with chronic pain. A common assumption is that significant others may selectively reinforce the patient’s pain behaviors (3). Thus, according to an operant model of chronic pain, several studies have found that solicitous responses from significant others are positively associated with greater levels of pain and disability

Supported by grants from the Spanish Ministerio de Ciencia y Tecnologı´a (BSO2001-0693), the Spanish Secretarı´a de Estado de Universidades (PR2002-0146 and PR2003-0255), the DFG (SFB 550/ C6), and the BMFT (network neuropathic pain). 1 Pedro Montoya, PhD: University of the Balearic Islands, Palma, Spain; 2Wolfgang Larbig, MD, Christoph Braun, ScD, Hubert Preissl, ScD: University of Tubingen, Tubingen, Germany; 3Niels Birbaumer, PhD: University of Tubingen, Tubingen, Germany, and University of Trent, Trent, Italy. Address correspondence and reprint requests to Pedro Montoya, PhD, Department of Psychology, University of the Balearic Islands, Carretera de Valldemossa, km 7.5, 07122 Palma, Spain. E-mail: [email protected]. Submitted for publication March 26, 2004; accepted in revised form August 23, 2004. 4035

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among patients with chronic pain (4–11). Furthermore, a recent controlled study designed to evaluate the efficacy of an operant pain treatment in FM has shown a significant reduction in pain, together with a reduction in the significant other’s solicitous behavior (6). In contrast, laboratory-based and clinical research studies have revealed a beneficial influence of social support in patients with chronic pain (12–16). To our knowledge, no studies have examined the effect of social support provided by the significant other on pain processing and brain activity in FM patients. Negative mood states, such as depression and anxiety, have been also repeatedly associated with chronic pain (17–20). In FM patients, it has been shown that negative affect is positively associated with decreased pain and tolerance thresholds (21,22). Thus, it seems that abnormal sensitivity in FM might also be modulated by emotional factors. Recently, a functional magnetic resonance imaging (MRI) study has further shown that our own brain activity can change when we are empathizing with the suffering of our partner (23). To our knowledge, there are, however, no data about the emotional modulation of pain processing in FM. The purpose of the present study was to assess the influence of the emotional context and the presence of a significant other on the processing of peripheral and central nociceptive input in patients with FM. It was hypothesized that the provision of social support by the presence of the patient’s significant other would be associated with changes in pain perception and in the brain’s processing of pain-related information. Emotional context was manipulated with the use of affective pictures, presenting them to the patients and asking the patients to empathize with the mood state elicited by the pictures. It was predicted that the simultaneous presentation of unpleasant stimuli would then alter the brain processing of non–pain-related information in FM patients. PATIENTS AND METHODS Patients. Eighteen patients with FM (16 women) and 18 patients with migraine without aura (15 women) ages 36–68 years participated in the study. The patients’ partners served as supportive significant others. FM patients were examined by an experienced rheumatologist (outside our unit), fulfilled the classification criteria of the ACR (1) with a minimum of 11 tender points (of a total of 18 specific tender points), and had a positive response on testing of tender points near the lateral humeral epicondyle on both sides of the body. Patients with migraine were examined by an experienced neurologist (WL), and fulfilled the criteria of the International Headache Society (24) for the diagnosis of

migraine with or without aura. These patients were under successful treatment and remained pain-free during the examination. Migraine headaches are usually described as an intense, throbbing, or pounding pain that is often located in the forehead, around the eye, or in the back of the head. Some characteristics of migraine patients that make them appropriate controls for comparison with FM patients are as follows: 1) migraine is characterized as a chronic pain condition consisting of recurrent attacks and usually aggravated by daily activities; 2) among the premonitory symptoms of a migraine attack are sleepiness, irritability, fatigue, and depression; and 3) migraine is more frequent among females than among males. None of the FM or migraine patients took any medication for at least 72 hours before the psychophysiologic assessment and the recordings of brain activity. Patients were informed about the objectives of the study and gave their signed informed consent. The study was conducted in accordance with the Declaration of Helsinki, and the protocol was approved by the Ethics Committee of the Medical Faculty of the University of Tubingen. Psychological pain assessment. All patients completed the German versions of the following instruments: the West Haven–Yale Multidimensional Pain Inventory (WHYMPI) (25), the Pain-Related Self-Statements Scale (PRSS) (26), and the Fibromyalgia Impact Questionnaire (FIQ) (27). The migraine patients also completed the FIQ so that both groups would have the same data. Quantitative sensory testing. Thermal perception and pain thresholds were measured by means of a thermal sensory analyzer (MSA Thermotest; Somedic Sales, Stockholm, Sweden) operated by a 25 ⫻ 50–mm (12.5 cm2) contact thermode. Perception and pain thresholds were assessed using the method of limits (mean of 3 measures). The skin surface was heated or cooled within a range of 5–52°C and a linear change gradient of 1°C/second. The baseline thermode temperature was always set to 32°C. The entire thermode surface was placed in contact with the skin of the elbow (2 cm above the lateral humeral epicondyle) and 2 fingers (the second and third fingers) on either the right or left side. The site and side of stimulation were both counterbalanced in all patients. The extremity that was rated by the FM patients as being more affected was chosen as the body side for thermal stimulation; the same body side was used for stimulation in an age-matched migraine patient. Thresholds for the perception of warmth, coldness, pain in response to heat, and pain in response to cold were determined as the temperature at which each subject started to feel warm, cold, heat pain, or cold pain at the body site being tested. Each threshold measurement was performed three times and the average value was adopted as the subject’s threshold. In half of the participants for each group, the cold perception and cold pain threshold assessment was applied first, followed by the warmth and heat pain threshold assessment. The assessment of thermal (either warmth or cold) perception threshold was always followed by the thermal (either heat or cold) pain threshold. Finally, as a further experimental manipulation, thermal threshold assessments were carried out under 2 different conditions: 1) with the patient alone in the recording room and 2) with the patient’s significant other present in the recording room. For the latter condition, the patient’s significant other

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was invited to sit down near the experimenter, facing the patient, and to follow the assessment procedure without verbal interaction. The patients’ significant others watched the threshold values on the computer screen, and no further instructions were given. Somatosensory stimulation and recording of brain activity. Brain activity was assessed through the recording of somatosensory evoked magnetic fields (SEFs) elicited by nonpainful tactile stimulation of the body surface. Tactile stimulation was delivered using a commercially available pneumatic stimulator (Biomagnetic Technologies, San Diego, CA), consisting of a small membrane attached to the body surface by a plastic clip and fixated with adhesive strips. Patients received 8 stimulation blocks, each of which consisted of 400 stimuli of 100-msec duration with an approximate pressure of 2 bars, and a variable interstimulus interval of 550 msec (⫾50 msec). Each stimulation block lasted ⬃3.5–4 minutes. Four blocks of pneumatic stimulation were applied to the elbow (2 cm above the lateral humeral epicondyle) of either the right or left arm; the other 4 blocks of stimulation were applied to the second finger of the left or right hand. Again, the extremity that was rated by the FM patient as being more affected was chosen as the side of the body to which the 8 blocks of pneumatic stimulation were applied; the same body side was used for the age-matched migraine patients. None of the study subjects reported discomfort or pain during the pneumatic stimulation. During pneumatic stimulation, the patients viewed a sequence of pictures selected from the International Affective Picture System (IAPS) (28). The IAPS is a set of photographs depicting a range of situations, from explicit sexual material to human injury and surgery to pleasant pictures of children and wildlife. Two sequences of affective slides (pain-related and neutral) were constructed, each consisting of 10 slides (6second presentation of each slide). Patients were instructed to pay attention to the slides and to imagine experiencing themselves in the situations depicted. During the pneumatic stimulation and slide presentation, the patient’s significant other was invited to sit down near the subject, allowing tactile contact between them, if desired, and to describe each slide aloud. Following the presentation of each sequence, patients were asked to rate the intensity of their pain on a 10-cm visual analog scale. The IAPS norms (28) for the pleasure ratings (0 ⫽ unpleasant and 9 ⫽ pleasant) on the pain-related and neutral images were 2.27 and 7.93, respectively. The IAPS norms for the arousal ratings (0 ⫽ low arousal and 9 ⫽ high arousal) on the two groups of images were 5.47 and 4.36, respectively. Brain activity triggered by pneumatic stimulation was recorded using a 151-channel whole-head magnetoencephalography (MEG) system (CTF151; Canadian Thinfilm, Port Coquitlam, British Columbia, Canada). Eight MEG recording blocks were obtained for each patient, combining the presence versus the absence of the patient’s significant other, the type of images viewed (pain-related versus neutral), and the stimulation site (elbow versus second finger). During each recording block, the MEG recording was made continuously, with a sampling rate of 312.5 Hz and a low-pass filter at 75 Hz. For offline analysis, MEG signals were segmented into epochs of 448-msec duration, using a prestimulus baseline period of 147.2 msec. Trials in which the amplitudes exceeded 1 picoTesla in the frontal channel next to the left eye were

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automatically deleted to control for eye blinks and eye movement artifacts. The remaining trials were averaged separately for each body site stimulated (elbow versus second finger), each picture sequence viewed (pain-related versus neutral), and each social support condition experienced during the MEG recording (patient alone versus presence of significant other), resulting in a total of 8 averages for each patient. Due to recording difficulties and problems with claustrophobia during the MEG recording procedure, data from 4 patients in each study group had to be excluded from the statistical analyses. In order to analyze the effects of the experimental manipulations on the amplitudes of the SEFs, the mean of the root mean square (RMS) was calculated in a time window between 0 and 70 msec after application of the stimulus, and these values were analyzed statistically. Data reduction and analysis. Basically, the study followed a randomized factorial mixed design with the following factors: group (FM versus migraine patients), social support (significant other’s presence versus alone), and body site (unilateral stimulation at elbow versus fingers). Additionally, for data obtained during MEG recordings, an emotional context (viewing pain-related versus neutral pictures) factor was also considered. Data were submitted to separate analyses of variance for repeated measures. The magnitude of effect sizes for the differences between the 2 levels of social support within each group was also calculated.

RESULTS Comparison of sociodemographic and pain characteristics. Table 1 shows the demographic and clinical pain characteristics for both patient groups. A nearly equal number of women were included in the FM and migraine groups (15 of 18 patients), and no significant difference in age was seen between the 2 groups. FM patients reported a minimum of 11 and a maximum of 18 tender points. No tender points were reported by the migraine patients. The FM patients also reported a significantly shorter duration of pain symptoms than did the migraine patients (t[34] ⫽ 3.33, P ⬍ 0.01). FM patients reported higher levels of pain than did migraine patients on the WHYMPI pain severity subscale (t[34] ⫽ 2.28, P ⬍ 0.05) and on the FIQ pain subscale (t[28] ⫽ 2.87, P ⬍ 0.01). In comparison with migraine patients, FM patients also reported a higher incidence of other somatic symptoms, as measured with the FIQ, such as fatigue (t[29] ⫽ 3.21, P ⬍ 0.01), morning tiredness (t[29] ⫽ 2.21, P ⬍ 0.05), and stiffness (t[27] ⫽ 2.91, P ⬍ 0.01). As might be expected, the global FIQ score was significantly higher in the FM group than in the migraine group (t[32] ⫽ 2.13, P ⬍ 0.05). The FM patients had fewer catastrophizing thoughts about pain than did the migraine patients (t[33] ⫽ 2.07, P ⬍ 0.05), as measured by the PRSS pain subscale.

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Table 1.

Demographic and pain characteristics of the study patients, including effect sizes* Characteristic

Age, years Duration of pain symptoms, years No. of tender points WHYMPI subscale scores (0–6 scale) Pain severity Pain interference Affective distress Social support Life control Self efficacy Responses of the significant other to the patients’ pain behaviors Solicitous Distracting Punishing Leisure activities Household activities Activities outside the house FIQ subscale scores Physical functioning (0–3 scale) No. of days felt bad (0–7 scale) No. of work days missed (0–7 scale) Job ability (10-cm VAS) Pain (10-cm VAS) Fatigue (10-cm VAS) Morning tiredness (10-cm VAS) Stiffness (10-cm VAS) Anxiety (10-cm VAS) Depression (10-cm VAS) Global FIQ score (0–100 scale) PRSS subscale scores (0–5 scale) Pain catastrophizing Active coping

Fibromyalgia patients (n ⫽ 18)

Migraine patients (n ⫽ 18)

Effect size

53.72 ⫾ 8.04 14.11 ⫾ 8.09† 14.78 ⫾ 3.51

54.94 ⫾ 10.60 24.56 ⫾ 10.56 –

0.12 0.99

3.54 ⫾ 1.08‡ 3.49 ⫾ 1.32 2.62 ⫾ 1.42 3.84 ⫾ 1.65 3.80 ⫾ 0.97 3.33 ⫾ 1.82

2.76 ⫾ 0.97 3.89 ⫾ 1.26 2.90 ⫾ 1.18 4.00 ⫾ 1.24 3.66 ⫾ 1.10 3.00 ⫾ 1.68

0.80 0.32 0.24 0.13 0.13 0.20

3.31 ⫾ 1.74 2.86 ⫾ 1.82 1.25 ⫾ 1.39 2.47 ⫾ 0.75 3.91 ⫾ 1.63 1.22 ⫾ 1.33

3.50 ⫾ 1.46 1.87 ⫾ 1.59 1.10 ⫾ 1.35 2.34 ⫾ 1.02 3.96 ⫾ 1.68 1.57 ⫾ 1.54

0.13 0.62 0.11 0.13 0.03 0.23

2.28 ⫾ 2.28 5.90 ⫾ 3.46 1.69 ⫾ 2.85 6.11 ⫾ 3.37‡ 6.83 ⫾ 2.36† 7.31 ⫾ 2.58† 7.09 ⫾ 3.24‡ 6.67 ⫾ 2.88† 3.41 ⫾ 2.55 2.98 ⫾ 3.06 52.23 ⫾ 17.87‡

3.02 ⫾ 2.76 4.21 ⫾ 2.34 0.72 ⫾ 1.20 3.12 ⫾ 3.21 4.09 ⫾ 2.87 3.88 ⫾ 3.36 4.34 ⫾ 3.67 3.02 ⫾ 3.89 2.92 ⫾ 2.71 2.09 ⫾ 2.35 35.82 ⫾ 26.28

0.27 0.72 0.81 0.93 0.95 1.02 0.75 0.94 0.18 0.38 0.62

2.33 ⫾ 0.79‡ 3.01 ⫾ 0.98

2.99 ⫾ 1.10 3.02 ⫾ 1.00

0.60 0.01

* Values are the mean ⫾ SD. WHYMPI ⫽ West Haven–Yale Multidimensional Pain Inventory; FIQ ⫽ Fibromyalgia Impact Questionnaire; VAS ⫽ visual analog scale; PRSS ⫽ Pain-Related Self-Statements Scale. † P ⬍ 0.01 versus migraine patients. ‡ P ⬍ 0.05 versus migraine patients.

No significant group differences were found on other WHYMPI subscales, which assessed pain interference, affective–cognitive factors (affective distress, life control, self efficacy), social support, perceived responses by the significant other (punishing, solicitous, distracting), or the patient’s activity level. Results of quantitative sensory testing. Table 2 summarizes the thermal perception and pain thresholds for each patient group, each stimulation site, and each social support condition. Overall, thresholds for pain in response to heat were significantly lower for FM patients than for migraine patients (F[1,30] ⫽ 4.41, P ⬍ 0.05), lower during stimulation at the elbow as compared with the fingers (F[1,30] ⫽ 8.51, P ⬍ 0.01), and lower when patients were alone than when their significant others were present (F[1,30] ⫽ 5.96, P ⬍ 0.05). Furthermore,

significant differences due to the presence of the patients’ partners were found only within the FM patient group during elbow stimulation (t[15] ⫽ 2.28, P ⬍ 0.05), showing lower thresholds for pain in response to heat when patients were alone than when their partners were present. No significant differences were found in the migraine patient group or during stimulation of the fingers. For the thresholds for pain in response to cold, the FM patients showed increased sensitivity compared with the migraine patients (F[1,30] ⫽ 6.97, P ⬍ 0.05). Overall, patients were more sensitive at the elbow than at the fingers (F[1,30] ⫽ 12.36, P ⬍ 0.001). In addition, a significant interaction between the factors group ⫻ body site (F[1,30] ⫽ 4.79, P ⬍ 0.05) was found. Again, FM patients showed significantly more pain sensitivity

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Table 2. Thermal perception and pain thresholds in the study patients, including effect sizes* Fibromyalgia patients (n ⫽ 16) Experimental condition, body site Pain in response to heat Elbow Fingers Pain in response to cold Elbow Fingers Perception of warmth Elbow Fingers Perception of coldness Elbow Fingers

Migraine patients (n ⫽ 16)

Patient alone

Significant other present

Effect size

Patient alone

Significant other present

Effect size

42.39 ⫾ 5.49 45.12 ⫾ 5.16

43.42 ⫾ 5.61 45.91 ⫾ 4.82

0.19 0.16

46.41 ⫾ 3.41 47.49 ⫾ 3.47

47.15 ⫾ 3.83 47.81 ⫾ 3.66

0.19 0.09

19.47 ⫾ 10.43 14.36 ⫾ 8.41

19.45 ⫾ 9.46 12.01 ⫾ 7.38

0.00 0.32

10.76 ⫾ 8.26 9.26 ⫾ 6.06

10.04 ⫾ 7.75 8.63 ⫾ 6.36

0.09 0.10

36.18 ⫾ 2.15 37.44 ⫾ 3.67

35.84 ⫾ 1.91 37.65 ⫾ 3.77

0.18 0.06

38.49 ⫾ 4.50 37.42 ⫾ 2.78

38.50 ⫾ 4.40 37.70 ⫾ 2.28

0.00 0.12

30.07 ⫾ 0.93 27.48 ⫾ 3.20

29.82 ⫾ 1.47 27.57 ⫾ 3.48

0.17 0.03

27.99 ⫾ 3.57 26.96 ⫾ 3.23

28.06 ⫾ 2.57 26.55 ⫾ 3.34

0.03 0.12

* Values are the mean ⫾ SD temperature (in degrees centigrade). See Patients and Methods for details of the testing method.

than did migraine patients. Post hoc analysis of the interaction effect revealed significant group differences between the FM and migraine patients for stimulation at the elbow (F[1,30] ⫽ 8.76, P ⬍ 0.01) but not at the fingers (F[1,30] ⫽ 3.14, P ⬎ 0.09). With respect to the social support factor, neither the main effects nor the interaction effects with the other factors yielded a significant difference in the thresholds for pain in response to cold. Overall, thresholds for pain in response to cold were higher, indicating greater pain sensitivity at the elbow (mean ⫾ SD 14.93 ⫾ 9.68°C) than at the fingers (11.06 ⫾ 7.01°C). Post hoc analysis revealed significant differences in the thresholds for pain in response to cold for the elbow compared with the fingers in the FM patients (t[15] ⫽ 3.02, P ⬍ 0.01) but not the migraine patients (t[15] ⫽ 2.01, P ⬎ 0.05). There were no other significant effects of the experimental conditions on the thermal thresholds, except for the perception of coldness for the factor body

site (F[1,30] ⫽ 10.83, P ⬍ 0.01), which revealed that in all patients, the elbow was more sensitive than the fingers. Subjective ratings of pain. Only data from FM patients were analyzed because none of the migraine patients reported changes in general levels of pain during the experiment. Overall, there was a significant increase in the subjective ratings of pain during the MEG recording session as compared with the prestimulus baseline values (t[15] ⫽ 2.31, P ⬍ 0.05). The mean ⫾ SD pain rating at the beginning of the MEG recording was 3.52 ⫾ 2.74 cm, and the average pain rating after each MEG recording block was 4.43 ⫾ 2.27 cm. In order to further analyze the influence of the experimental manipulations on changes in subjective ratings of pain in the FM patients, changes in ratings from the prestimulus baseline values were calculated for ratings obtained after each block of MEG recordings. Significant effects were found for the emotional con-

Table 3. Changes from prestimulus baseline ratings of subjective pain during magnetoencephalographic recording, including effect sizes* Fibromyalgia patients (n ⫽ 16) Experimental condition, body site Viewing pain-related images Elbow Finger Viewing emotionally neutral images Elbow Finger

Patient alone

Significant other present

Effect size

1.58 ⫾ 2.35 1.38 ⫾ 1.84

0.91 ⫾ 1.48 1.16 ⫾ 2.38

0.45 0.09

0.90 ⫾ 1.99 0.86 ⫾ 2.40

0.21 ⫾ 1.61 0.28 ⫾ 1.82

0.43 0.32

* The emotional context during presentation of tactile stimuli was manipulated by presenting aversive, pain-related pictures and neutral pictures and asking the patients to imagine themselves experiencing the situations depicted. Values are the mean ⫾ SD cm (on a 10-cm visual analog scale). See Patients and Methods for details of the testing method.

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Figure 1. Somatosensory evoked magnetic fields following pneumatic stimulation of the elbow and the finger. Superimposed waveforms recorded by the 151 magnetoencephalographic sensors in the fibromyalgia (n ⫽ 14) and migraine (n ⫽ 14) patients under the 2 experimental conditions of social support: patient alone and significant other present. Time 0 represents the point of pneumatic stimulation of the elbow or finger.

text (F[1,15] ⫽ 11.44, P ⬍ 0.01) and social support (F[1,15] ⫽ 5.65, P ⬍ 0.05) factors. These effects indicated a significant augmentation of pain when FM

patients were viewing pain-related images in comparison with neutral images, as well as a reduction in the severity of pain when they were given social support through the

Figure 2. A, Superimposed waveforms recorded by the 151 magnetoencephalographic sensors and B, localization of source generators overlaid on a magnetic resonance imaging scan in a representative patient with fibromyalgia examined under the 4 experimental conditions. Time 0 represents the point of pneumatic stimulation of the elbow or finger. Contralateral activation of the primary somatosensory cortex during pneumatic stimulation of the finger and the elbow under the 4 experimental conditions activated the following areas: finger stimulation with patient alone (dark blue), finger stimulation with significant other present (turquoise), elbow stimulation with patient alone (dark red), and elbow stimulation with significant other present (fuchsia).

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Table 4. Root mean square values during magnetoencephalographic recording in the study patients, including effect sizes* Fibromyalgia patients (n ⫽ 14) Patient alone

Significant other present

Effect size

Patient alone

Significant other present

Effect size

pain-related images emotionally neutral images

13.15 ⫾ 5.22 14.27 ⫾ 7.09

12.03 ⫾ 4.97 13.12 ⫾ 7.06

0.23 0.16

14.08 ⫾ 4.66 15.17 ⫾ 5.64

14.25 ⫾ 6.59 12.21 ⫾ 3.53

0.03 0.84

pain-related images emotionally neutral images

24.99 ⫾ 8.19 25.51 ⫾ 9.43

24.93 ⫾ 9.24 25.60 ⫾ 9.53

0.01 0.01

19.15 ⫾ 6.93 19.68 ⫾ 8.55

21.58 ⫾ 7.93 20.23 ⫾ 7.58

0.31 0.07

Body site, experimental condition Elbow Viewing Viewing Finger Viewing Viewing

Migraine patients (n ⫽ 14)

* Values are the mean ⫾ SD root mean square values for global field power (in femtoTesla/cm2).

presence of their significant others. Table 3 shows that a minor increment in pain (compared with prestimulus baseline) was observed when patients were viewing neutral pictures with their significant others and stimulation was at the elbow. Somatosensory evoked fields. The earliest prominent activity peak of the magnetic brain response was observed within the time window of 30–70 msec after stimulus presentation (Figure 1). The cortical representations of the response to elbow and finger stimulation assessed by source modeling of this activity peak showed that the evoked magnetic activity in the time window around the activity peak was generated in the contralateral primary somatosensory cortex (Figure 2). Table 4 summarizes the mean RMS values in the time window between 0 and 70 msec after stimulus presentation during the different blocks of MEG recordings. Analysis of variance including all the factors showed significant effects for body site (F[1,26] ⫽ 33.74, P ⬍ 0.0001) and body site ⫻ social support (F[1,26] ⫽ 4.95, P ⬍ 0.05); as well as marginally significant effects for body site ⫻ group (F[1,26] ⫽ 3.47, P ⫽ 0.074). No significant effects were found for the factor emotional context. Basically, these effects revealed that brain activity elicited upon stimulation of the elbow was significantly lower than that elicited upon stimulation of the finger. Post hoc analysis only showed a significant effect of social support on SEFs elicited upon elbow stimulation (F[1,26] ⫽ 9.05, P ⬍ 0.01). Brain activity elicited by elbow stimulation was significantly reduced when the patient’s partner was present as compared with when the patient was alone. Separate analyses of variance for each patient group revealed that this effect of social support on brain activity elicited by elbow stimulation was more pronounced in FM patients (F[1,13] ⫽ 8.37, P ⬍ 0.05) than in migraine patients (F[1,13] ⫽ 3.51, P ⫽ 0.08).

DISCUSSION The main goal of the present study was to analyze the influence of social support and emotional context on the processing of nociceptive and non-nociceptive information in FM patients as compared with migraine patients. The data suggest that social support mediated by the presence of the patient’s significant other may influence the processing of nociceptive and nonnociceptive information in FM. Stimulation of a painful body site, such as the elbow, in the presence of the patients’ significant others in the laboratory led to significant reductions in pain sensitivity, pain severity, and brain-related activity as compared with stimulation of the elbow in the absence of the significant others. In contrast, no significant effects of social support were observed in migraine patients. No effects were shown when stimuli were applied at a nonpainful body site, such as the finger, in either of the 2 groups. Our findings are consistent with previous research demonstrating that social support is associated with lower levels of acute pain under different clinical conditions, such as labor pain (29), cancer pain (13), and cardiac pain (30,31). In addition, there is also evidence that patients with chronic pain who have strong marital relationships report less pain-related disability following interpersonal stress (15). It has been hypothesized that the presence of a supportive other may diminish one’s appraisal of threat, which in turn might influence one’s experience of pain by reducing the negative emotions and expectations of pain or by increasing the positive affect. It has also been shown that the presence of a significant other can protectively buffer the individual neuroendocrine and cardiovascular reactions associated with stressful life events (32,33). In our study, the relatively high scores for the WHYMPI subscales of social support, solicitous, and distracting indicated that

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FM patients perceived their social environments as positive. Another plausible explanation for the beneficial effect of the presence of significant others is that the presence of a supportive person helped to distract patients from their experience of pain. In our study, it might be speculated that the presence of the significant other acted as a distracting mechanism by diminishing pain and reducing brain activity elicited by tactile stimulation at a painful tender point. Current experimental evidence in healthy subjects suggests that directing the attention away from pain by using highly demanding cognitive tasks leads to reduced pain perception and decreased activation in several brain regions involved in pain processing (34,35). A recent functional MRI study in healthy subjects demonstrated the importance of empathy in the modulation of emotional brain responses in the perception of pain (23). If attentional effects are responsible for the pain modulation seen in the present study, then they must act through an early, preconscious sensory mechanism. Evoked magnetic fields studied in this experiment had a latency of 20–70 msec, representing the primary evoked cortical response to somatic stimulation. This may partly explain the fact that voluntary control of pain by patients with chronic pain is probably impossible. It also showed that social context factors act on excitability thresholds in the central nervous system without conscious cognitive processing. The site specificity of the pain-reducing effect of the presence of a significant other supports our notion of an automatic, but highly selective, attentional mechanism, involving the first sensory-discriminative component of pain analysis in the central nervous system. In contrast, the insensitivity of migraine patients to social support probably indicates less interaction between disease processes and psychological factors or a closer relationship with hormonal factors in the etiology of migraine. Overall, we also found a significant enhancement of pain intensity ratings in FM patients when they were viewing pain-related pictures as compared with neutral ones, both sets of which were chosen from the IAPS collection (28). The psychometric properties of the pictures selected for the present study clearly indicated that they differed in terms of emotional strength, but were quite similar in terms of the arousal ratings. Thus, our finding suggests that there is a modulatory effect of the affective context upon the subjective perception of current pain in FM patients. To our knowledge, this is the first empirical demonstration that experiencing a negative mood state caused by viewing aversive or

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pain-related pictures can also increase the perception of pain in FM patients. Previous studies demonstrating that sensory reflexes, such as the acoustic startle and the eye-blink reflex, can be modulated by the emotional context in which they occur (18,36) are consistent with our findings. Recently, Phillips et al (37) demonstrated that the intensity of the negative emotional context could modulate neural responses to esophageal stimulation, especially within the dorsal anterior cingulate gyrus and anterior insula. Nevertheless, we failed to find any effect of emotional context on brain processing related to nonpainful body stimulation. It is possible that, contrary to the study by Phillips et al (37), the somatic stimulation used in the present study was not directly responsible for the experience of pain among FM patients, and therefore no effect of emotional context on brain processing associated with that stimulation could be seen. In the present study, we also found that the FM patients showed higher levels of pain sensitivity at the elbow (a painful tender point in FM patients), but not at the finger (considered by all patients to be a nonpainful body site), as compared with the migraine patients. These findings are consistent with reported evidence suggesting that FM patients display lower thresholds for thermal stimuli than do healthy controls (21,38–40). Our migraine patients were not experiencing headache during the experiment, but they experienced chronic pain significantly longer than did the FM patients. We also did not find any group differences in pain interference as assessed by the WHYMPI, and the scores were quite similar to those reported elsewhere for patients with chronic pain (6,41). Significant differences were found on some of the FIQ subscales, indicating that FM patients were more affected by the experience of actual pain than were migraine patients. Nonetheless, it is noteworthy that FM patients reported significantly less catastrophizing thoughts than did migraine patients. It is possible that a longstanding history of pain would lead to increased negative pain-coping strategies or vice versa. This would be consistent with recent suggestions that FM is not a discrete entity and that the identification of subgroups of FM patients would be helpful for the development of specific and individual therapies (6,42,43). In this regard, a recent study by Giesecke et al (42) identified 3 subgroups of FM patients based on levels of catastrophizing, mood ratings, and patterns of pressure–pain sensitivity. Our FM sample was characterized by a moderate-to-low level of catastrophizing thoughts about pain and low levels of affective distress,

PAIN PROCESSING AND BRAIN RESPONSES IN FIBROMYALGIA

together with moderately increased sensitivity to thermal pain at an already painful site. It might be expected that this cluster of FM patients would obtain greater benefit from social support than would other patient clusters, with higher mood ratings, pain catastrophizing levels, and pain sensitivity at both painful and nonpainful body sites. Further research will be necessary to examine the extent to which subgrouping of FM patients would help our understanding of the maintenance mechanisms of this complex pain condition. Some shortcomings and limitations of this study must also be considered. First, all subjects were tested at a body site that only the FM patients, and not the migraine patients, considered to be tender. It is therefore quite probable that different results would be obtained if the most tender site of the body in the migraine patients were to be used for pain testing. Additional research is needed to determine whether this finding can be generalized to other body sites and for other types of chronic pain conditions. Second, previous research has shown that the method of limits, which we used for pain threshold assessments, may be influenced by the patient’s psychological state in FM (44). Thus, it cannot be ruled out that the observed influence of social support on subjective pain sensitivity was mediated by the mode of presentation of the stimuli. The high concordance between central nervous system measures and pain sensitivity is evidence against such a possibility. A random paradigm for threshold measurements that would better control for expectancy bias may constitute a viable alternative. Third, although the statistical analysis of the influence of social support on pain processing revealed significant differences between the 2 experimental conditions in FM patients, the magnitudes of the effects were rather small. Therefore, caution should be taken when generalizing the present findings to clinical settings and populations, and replication of our results is necessary. In summary, our data revealed a significant influence of social support and emotional context on pain processing among patients with fibromyalgia. These findings indicate the importance of considering a biopsychosocial model in understanding the brain mechanisms involved in the origin and maintenance of chronic pain in FM.

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