Both pain and EEG response to cold pressor stimulation occurs faster in fibromyalgia patients than in control subjects
Introduction
Fibromyalgia syndrome is characterized by a history of widespread musculoskeletal pain in the upper and lower body, in combination with tenderness on digital palpation at 11 or more of the defined 18 specific tender point sites (Wolfe et al., 1990). The prevalence exceeds 2% in the general population (Wolfe et al., 1995), while mostly women are affected. In patients with fibromyalgia syndrome, a lower pain threshold has repeatedly been shown (Mikkelsson et al., 1992), suggesting abnormal peripheral or central processing of somatosensory stimuli (Coderre and Katz, 1997). Alternatively, a particular state of mind, involving mood, expectation and fear of pain might facilitate perception and processing of potentially painful stimuli. Studies of painful laser-evoked brain potentials (LEP) (Lorenz et al., 1996) found lowered pain thresholds and increased N170 potentials in fibromyalgia, which may indicate abnormal low-level processing of noxious stimuli. Gibson et al. (1994) reported a multimodal lowering of pain thresholds in fibromyalgia. However, in contrast to LEP pain, which is described as short and sharp in quality, ‘clinical pain’ (Chen, 1993), and fibromyalgia pain in particular, is enduring (tonic), deep and poorly localized, and in these aspects may more closely resemble cold pressor test (CPT) pain (Chen, 1993).
EEG studies of evoked pain in general have been reviewed by Bromm and Lorenz (1998). In brief, phasic (laser-evoked) pain produces a biphasic potential consisting of a late negative (N2, 120 ms) and a positive (P2, 230 ms) component, with a maximum at the vertex. These potentials are thought to rely on A-fiber transmission. Repeated laser stimulation may induce a prolonged sensation of pain (‘second pain’), possibly through ‘C-fiber wind-up’ (Bromm and Lorenz, 1998); however, the subjective quality is more localized and burning than CPT stimulation. In order to observe the C-fiber-related very late potentials (a positivity at 1300 ms), A-fiber transmission (‘first pain’) must be blocked. Tonic pain evoked by CPT stimulation may not lend itself to evoked potential methodology; however, studies using spectral power in good agreement report a diffuse increase in low frequency (delta and theta) power, most prominent over central, as well as somatosensory, cortex (Backonja et al., 1991, Chen, 1993, Chen et al., 1998).
The present study analyzes EEG power changes during CPT in fibromyalgia patients and control subjects, and contrasts CPT stimulation with pain imagery and mental arithmetic. The hypotheses were:
- 1.
Fibromyalgia-syndrome patients process pain upon CPT stimulation faster and more effectively than control subjects. Evidence for this would be increased scores on a pain rating scale, as well as earlier appearance of pain-related EEG states in spectral power analysis.
- 2.
Pain expectation and imagination is involved in the increased perception of pain in patients. Evidence for this may be similar EEG power patterns during pain imagery and CPT.
- 3.
In the patient group, subjective pain ratings and pain tolerance correlate with depression and anxiety scores.
Tonic pain was evoked by the CPT, as this is a well-established method. The dependent variable in the study was total EEG power. We used total power augmented by quadrant-wise analysis, as the above-cited studies reported a diffuse increase in low-frequency power measures during pain.
Section snippets
Subjects
Right-handed subjects (n=20, median age 50 years, 18 females, 2 males), suffering from fibromyalgia syndrome according to the American College of Rheumatology (ACR) criteria (Wolfe et al., 1990), and 21 healthy control subjects (median age 46 years, 17 females, 4 males), were recruited. Informed consent was obtained in every case. The control subjects were recruited both from the hospital staff and, using a newspaper advertisement, from the population of Tübingen. Right-handedness was
Time to THR and TOL and pain intensity ratings
During the CPT, patients identified pain significantly earlier [time from IMS to THR, t-test, F(39)=8.06, P<0.01], and withdrew their arms earlier [time from IMS to TOL, t-test F(39)=14.53, P<0.001] (Table 1). Patients did not differ from control subjects in their pain intensity ratings (CPT and imagery), and both groups rated pain upon CPT stimulation higher than imagined pain [F(2,78)=33.21, P<0.001]. Imagined pain intensity did not change after the CPT experience. STAI or CES-D and pain
Discussion
The study was motivated by the interest to analyze and correlate subjective awareness of pain and EEG power spectra during CPT-evoked pain in fibromyalgia patients, and to compare this with findings in healthy control subjects. The CPT was chosen as the stimulus because it evokes deep and enduring pain resembling fibromyalgia pain.
The main findings were the following. The cold water stimulus was perceived much earlier as painful and intolerable by the patients. Meanwhile, subjective levels of
Acknowledgements
We wish to thank the subjects who participated in the experiment. The study was supported by the University of Tübingen (forTüne grant F1331124).
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