Glenn A. McCain

Generalized hypervigilance in fibromyalgia: evidence of perceptual amplification.

&NA; The hypervigilance model of pain perception states that chronic pain patients have a heightened sensitivity to pain (e.g. low threshold and tolerance) because of increased attention to external stimulation and a preoccupation with pain sensations. This study tested the hypothesis that individuals with fibromyalgia, a chronic pain disorder of undetermined origin, have a generalized hypervigilant pattern of responding that extends beyond the pain domain. Twenty fibromyalgia out‐patients, 20 rheumatoid arthritis (RA) patients, and 20 normal controls served as subjects. The RA and normal control subjects were age and sex matched to the fibromyalgia patients. Subjects were tested for pain tolerance, pain threshold, and noise tolerance and were asked to complete a number of questionnaires that assessed hypervigilance. As predicted, the responses of the fibromyalgia patients to both the pain and auditory stimuli were consistent with the generalized hypervigilance hypothesis. These patients had significantly lower threshold and tolerance values than the RA patients, who in turn, had lower values than the normal control subjects. The results of the psychological questionnaires revealed that the fibromyalgia and RA patients preferred lower levels of external stimulation than the control subjects. The outcome of this study supports the generalized hypervigilance hypothesis, suggesting that fibromyalgia patients have a perceptual style of amplification. The implications of these findings for understanding the role of biological, cognitive, and perceptual factors in pain disorders are discussed.

Multi-method assessment of experimental and clinical pain in patients with fibromyalgia

&NA; Experimental measures of responsiveness to painful and non‐painful stimuli as well as measures of typical and present clinical pain were assessed in 26 female patients with fibromyalgia and in an equal number of age‐matched healthy women. Pressure pain thresholds, determined by means of a dolorimeter, were lower in the patients compared to the control subjects both at a tender point (trapezius) and at a non‐tender control point (inner forearm). The same was true for the heat pain thresholds, measured using a contact thermode. In contrast, the pain thresholds for electrocutaneous stimuli were decreased only at the tender point. The detection thresholds for non‐painful stimuli (warmth, cold and electrical stimuli) seemed to be less affected in the fibromyalgia patients, with only the detection threshold for cold being lower at both sites. Tender points were more sensitive than control points for mechanical pressure. The reverse was found for the other modalities which were tested. Although the 3 experimental pain thresholds showed patterns of either generalized or site‐specific pain hyperresponsiveness, the between‐methods correlations were not very high. While the correlations between the experimental pain thresholds and the various measures of clinical pain (Localized Pain Rating, McGill Pain Questionnaire) in the patients were generally low, there were significant negative correlations between pressure pain thresholds at the two sites and the level of present pain assessed by the Localized Pain Rating. We conclude that a pattern of pain hyperresponsiveness, generalized across the site of noxious stimulation and across the physical nature of the stressor, is associated with fibromyalgia. The pattern of hyperresponsiveness appears to involve both peripheral factors (e.g., sensitization of muscle nociceptors) and central ones (e.g., hypervigilance or a lack of nociceptive inhibition).

Cytokine production and lymphocyte transformation during stress

The production of interleukin-1 beta (IL-1 beta) and interferon-gamma (IFN gamma) and blast transformation in peripheral blood mononuclear cells were assessed in medical students writing an academic examination. Blood samples were obtained on three occasions: (1) 1 month prior to the examination during a period of relatively low academic demand; (2) immediately after the examination; and (3) 10 days later. Results indicated that immune responses were significantly different immediately after the examination compared with the baseline and postexam measures. Lymphocyte responsiveness to both concanavalin A and pokeweed mitogen was decreased, as was the production of IFN gamma, supporting earlier reports of immunosuppression after relatively commonplace stressors. In contrast to predictions, IL-1 beta production was significantly elevated after the examination. Cortisol levels were also measured, but did not change across the three sample points. Our finding of an increase in IL-1 beta production suggests that stress may have different effects on different cell populations by enhancing the responses of monocytes and depressing those of lymphocytes.

Toward an integrated understanding of fibromyalgia syndrome. I. Medical and pathophysiological aspects

&NA; Fibromyalgia syndrome (FS) is a chronic pain disorder characterized by diffuse musculoskeletal soreness, stiffness, non‐restorative sleep and psychological disturbance. At present, much about the etiology, pathological mechanisms and course of FS are unknown. Indeed, standardized diagnostic criteria have only been recently agreed upon. The present paper is the first of a two‐part series which reviews the extant empirical literature concerning FS, with a view to arriving at an integrated understanding of the syndrome. The present paper describes the clinical presentation of FS and historical conceptualizations of the disorder. Available research on pathophysiological mechanisms in FS is then presented. In this section we have included literature concerning histology of muscle, sleep architecture, neurotransmitter anomalies and neuropeptide involvement in FS symptomatology.

Role of physical fitness training in the fibrositis/fibromyalgia syndrome

Cardiovascular fitness training has been suggested as a treatment for the fibrositis/fibromyalgia syndrome. Thirty-four patients with fibrositis/fibromyalgia who met Smythes original criteria were randomly assigned to enter either a cardiovascular fitness training program or a program consisting only of flexibility exercises. Patients met in supervised groups three times weekly for a 20-week observation period. The cardiovascular fitness group underwent gradual heart rate-elevated training using a bicycle ergometer and achieved a 29.1 +/- 24.4 percent increase in peak work capacity at 170 beats per minute (PWC-170). Patients undergoing flexibility training had a net reduction in their PWC-170 scores of 4.3 +/- 9.4 percent. Patients in the cardiovascular fitness group had statistically significant improvements in the visual analogue pain scale of current pain intensity; total myalgic scores in which pain thresholds at five fibrositic tender points selected for acceptable intra-rater and inter-rater reliability were measured using a dolorimeter; percentage total body area affected as measured by self-administered pain diagrams; and patients and physicians global assessment scores. Psychologic profiles as measured by Symptom Checklist-90R also improved in the cardiovascular fitness group compared with the flexibility training group. It is concluded that cardiovascular fitness training is feasible in patients with fibrositis/fibromyalgia and that such training improves subjective measurements of pain-reporting behavior. A theoretic basis for improvements in pain measurement scales and psychologic profiles is discussed in light of recent literature.

Toward an integrated understanding of fibromyalgia syndrome. II, Psychological and phenomenological aspects

&NA; The present paper is the second of a 2‐part series in which extant empirical literature concerning fibromyalgia syndrome (FS) is reviewed in order to provide a preliminary approach to forming an integrated understanding of the syndrome. Research on psychological disturbance in FS is reviewed with particular emphasis on affective dysfunction among FS patients. The phenomenology of FS is then described. We attempt to suggest that FS represents a quantitatively and qualitatively experience distinct from similar chronic pain syndromes. Substantive findings in FS research are summarized in the final section and potential ways in which these findings might be integrated to provide a more cohesive model for future research are suggested.

The concept of primary fibromyalgia (fibrositis): clinical value, relation and significance to other chronic musculoskeletal pain syndromes.

&NA; PFS, MPS and TMPDS can be identified using positive diagnostic criteria among patients presenting with chronic pain. A directed rather than exhaustive search for organic diseases known to coexist with these syndromes is usually all that is necessary. Criteria are presently empirical but do identify homogeneous populations of patients for study and treatment. Some patients, however, provide examples of overlap and it may be useful to think of CMPS in terms of the Venn diagram depicted in Fig. 2. In this report we have attempted an initial classification for a group of common and perplexing chronic pain disorders of the musculoskeletal system which at present have no identifiable cause. Previous investigations have been hampered by erroneous pathological concepts, heterogeneous patient populations and poor study design particularly with respect to treatment modalities. We hope that this classification, while empirical, will lead to needed epidemiological studies outlining the similarities and differences between these clinically observable and different musculoskeletal syndromes. We hope, further, that it will foster cooperation between different medical disciplines so that clinical biases might be tested in light of current concepts of the scientific method.

Pain and functional limitations in individuals with rheumatoid arthritis.

The focus of this investigation was to determine if health status variables such as pain and functional limitations are correlated with an individuals occupational profile (work, activities of daily living and leisure), and psychological adjustment (depression, anxiety and dissatisfaction with life). This study reports our findings for 143 individuals with rheumatoid arthritis (RA). It would appear from the results of this study that functional limitations have an even greater impact on individuals with RA than pain. This findings and its implications are discussed.

The use of topical 4% lidocaine in spheno-palatine ganglion blocks for the treatment of chronic muscle pain syndromes : a randomized, controlled trial

&NA; To assess the efficacy of 4% topical lidocaine in spheno‐palatine blocks, a randomized controlled trial was carried out on patients with chronic muscle pain syndromes. Sixty‐one patients (42 with fibromyalgia (FM) and 19 with myofascial pain syndrome (MPS)) completed the trial. Outcome measures included pain intensity, a daily pain diary, headache frequency, sensitivity to pressure using a dolorimeter, anxiety, depression, and sleep quality. Patients were randomized to receive either 4% lidocaine or sterile water (placebo) 6 times over a 3‐week period. Both subjects and investigators were blind to treatment allocation. The results showed that 4% lidocaine had no superiority over placebo in any of the outcome measures. Twenty‐one subjects (35%) showed a decrease in pain which was greater than 30% of their baseline value. Of these 21 subjects, 10 received lidocaine and 11 received placebo. These data suggest that, in this population, 4% lidocaine is no better than placebo in the treatment of chronic muscle pain.

The modulation of interleukin 1 production by interferon gamma, and the inhibitory effects of gold compounds

We have studied the in vitro effects of gold sodium thiomalate (GST) and auranofin (Auf) on the production of interleukin 1 (IL1) expressed as thymocyte co-stimulatory activity (TCSA), and interleukin 1 beta (IL1 beta) as modulated by interferon gamma (IFN gamma). Adherent cells (ADC), of which 80% were monocytes, were obtained from human peripheral blood, and stimulated with lipoprotein polysaccharide (LPS) for 24-48 h. TCSA and IL1 beta production by fresh ADC (0-24 h) was significantly higher than that of aged ADC (24-48 h). The addition of IFN gamma to ADC cultures, however, maintained the capacity of aging ADC to respond optimally to LPS. The addition of GST or Auf inhibited this modulatory effect of IFN gamma, resulting in a marked reduction of TCSA and IL1 beta production. The effects of IFN gamma on the production of IL1 may be important in the pathogenesis of rheumatoid arthritis (RA). The inhibition by GST and Auf of IFN gamma modulation may contribute to the therapeutic efficacy of these drugs in RA.