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PubMed1996

Fibromyalgia and migraine, two faces of the same mechanism. Serotonin as the common clue for pathogenesis and therapy.

In this study fibromyalgia sufferers were randomly administered a combination of monoamine-oxidase inhibitors (MAOIs)-A/B with 5-HTP, 5-HTP alone, MAOIs-A/B alone, or the tricyclic drug amitriptyline in order to compare the efficacy of these treatments. The benefits on the painful syndrome were assessed by using Visual Analogic Scale score rating from 0 to 4. The combination of MAOIs with 5-HTP significantly improved fibromyalgia syndrome as determined by Visual Analogic Scale whereas the other treatments yielded poorer benefits. No subject withdrew from the trial due to adverse effects, even if some sleep disturbances and mild stomach-ache were reported. The tolerability of the association MAOIs/5-HTP was good, although a transient cheese effect occurred in one of the patients treated with MAOIs as well as in a patient treated with the association MAOIs and 5-HTP. No one of these two cases was due to pharmacological dietetic mistake of the patient. In both the cases the transient hypertension was associated to very dramatic emotional events. The benefits obtained by using the combination of MAOIs with 5-HTP can be explained with a treatment-induced enhancement of aminergic and serotonergic transmission. The recently shown high prevalence of migraine in the population of fibromyalgia sufferers, suggests a common ground shared by fibromyalgia and migraine. Migraine has been demonstrated to be characterized by a defect in the serotonergic and adrenergic systems. A parallel dramatic failure of serotonergic systems and a defect of adrenergic transmission have been evidenced to affect fibromyalgia sufferers too. Enhancing serotonergic analgesia while increasing adrenergically mediated analgesia seems to be an important tool in fibromyalgia. Treatment consisting with the association MAOIs/5-HTP is aimed at enhancing serotonergic/adrenergic transmission by inducing an up-regulation of serotonergic/adrenergic receptors and a simultaneous increase of serotonin levels in the central nervous system.

5-Hydroxytryptophan↗
PubMed1997

Adverse drug reactions and debrisoquine/sparteine (P450IID6) polymorphism in patients with fibromyalgia.

OBJECTIVE: To assess the frequency of adverse drug reaction in patients with fibromyalgia in relation to medications prescribed for this condition. To evaluate the potential role of the P450IID6 phenotype in the pathogenesis of these adverse drug reactions. METHODS: Thirty-five patients with fibromyalgia were assessed using a structured questionnaire with demographic and clinical data and perceived adverse drug reactions. A sample of 60 patients with rheumatoid arthritis and 62 patients with localized back pain served as controls. The P450IID6 phenotype was determined for each of the fibromyalgia patients. RESULTS: Overall, 141 patients had used NSAID and 79 (56%) of them reported adverse effects. Antidepressant drugs were used by 68 patients and 35 (51%) patients had adverse effects. Muscle relaxant drugs were used by 48 patients and 15 (31%) of them reported side effects. Analgesics were used by 122 patients and 22 (18%) had experienced adverse effects. Statistical differences in the frequency of adverse effects were found with antidepressant drugs in the fibromyalgia group, compared with rheumatoid arthritis (p=0.01) and back pain (p=0.02). Four of the 35 patients (11.4%) had a metabolic ratio (M.R.) greater than 0.30 (log M.R.= -0.52) indicative of the poor metabolizers (PM) phenotype. M.R. varied from 0.005 (log M.R. = -2.30) to 4.99 (log M.R. = 0.70). CONCLUSIONS: The problem of adverse drug reactions in fibromyalgia patients does not appear to correlate with the PM phenotype of the P450IID6 oxidative enzyme. It also is unlikely that altered xenobiotic detoxification attributable to this PM phenotype would have a significant role in the development of fibromyalgia.

Adult↗
PubMed1997

Psychological disturbance in fibromyalgia: relation to pain severity.

Fibromyalgia is a form of nonarticular rheumatism characterized by musculoskeletal aching and tenderness on palpation. The role of psychological factors in fibromyalgia has been controversial. The aim of this study was to evaluate the relationship of fibromyalgia to the intensity of anxiety and depression and to determine the correlation between psychological disturbances with disease duration and pain severity. Thirty-nine patients with fibromyalgia and 36 healthy controls were included in this study. Beck depression inventory, State and trait anxiety inventory and Beck hopelessness scale were used to evaluate psychological disturbances. Visual analog scale was used to determine pain intensity. We found a significant difference in the psychological status between patients with fibromyalgia and control subjects as measured by Beck depression inventory and trait anxiety inventory; 35.9% of the patients scored higher than the cut-off score on the Beck depression rating scale. Pain severity was found to be correlated with trait anxiety inventory scores. These results suggest that somatic expression of depression is an important difference between fibromyalgia and control groups. The difference between state and trait anxiety inventory reflects that current anxiety is not secondary to pain but trait anxiety is possibly causally related to pain.

Adolescent↗
PubMed2007

[Fibromyalgia. Diagnostics--disease approach--therapy].

Fibromyalgia is a complex of symptoms predominantly affecting females and consisting of widespread pain. Etiology and pathogenesis are not sufficiently known yet, however, there is the assumption that fibromyalgia is looked at as being an illness with biological, psychological, and social aspects. Therefore, the treatment of fibromyalgia calls for a multimodal therapy approach. The importance of fibromyalgia has been recognized within the German health system by creating the new ICD code M79.70 and by assigning fibromyalgia its own rheumatologic DRG (I79Z). In future research of fibromyalgia special attention needs to be placed upon gender-specific problems.

Combined Modality Therapy↗
PubMed2002

The effects of balneotherapy on fibromyalgia patients.

Fibromyalgia syndrome (FMS) is a very common rheumatological diagnosis. There are various treatment modalities. This study was planned to investigate the effects of balneotherapy in the treatment of FMS. A total of 42 primary fibromyalgia patients diagnosed according to American College of Rheumatology criteria were included in the study. Their ages ranged between 30 and 55 years. Patients were randomly assigned to two groups. None of them had had a cardiovascular disease before. Group 1 n=22) received 20-min bathing, once a day and five times per week. Patients participated in the study for 3 weeks (total of 15 sessions). Group 2 (n=20) was accepted as the control group. Patients were evaluated by the number of tender points, Visual Analogue Scale for pain, Beck's Depression Index for depression, and Fibromyalgia Impact Questionnaire for functional capacity. Measurements were assessed initially, after the therapy, and at the end of the 6th month. In group 1, there were statistically significant differences in numbers of tender points, Visual Analogue scores, Beck's Depression Index, and Fibromyalgia Impact Questionnaire scores after the therapy program (P<0.001). Also, 6 months later in group 1, there was still an improvement in the number of tender points (P<0.001), Visual Analogue scores, and Fibromyalgia Impact Questionnaire (P<0.005). But there was not a statistical difference in Beck's Depression Index scores compared to the control group (P>0.05). Patients with FMS mostly complain about pain, anxiety, and the difficulty in daily living activities. This study shows that balneotherapy is effective and may be an alternative method in treating fibromyalgia patients.

Activities of Daily Living↗
PubMed2007

Which of the three different tender points assessment methods is more useful for predicting the severity of fibromyalgia syndrome?

Digital palpation, myalgic scoring and dolorimetry are frequently used to count tender points in fibromyalgia syndrome. We aimed to investigate the probable relation between tender points count and fibromyalgia impact questionnaire and to assess which of the tender point counting methods is the most successful in predicting the severity of the disease. Tender point areas of 36 patients with fibromyalgia syndrome were assessed with three methods which are myalgic scoring, digital and dolorimetric tender points counting methods. Fibromyalgia impact questionnaire was used to measure the disease severity. The correlation between each of the assessment methods and fibromyalgia impact questionnaire was investigated. The mean count of digitally evaluated tender points was 14.86 +/- 2.67 and by dolorimetry was 11.81 +/- 4.48. The mean total myalgic score was found to be 24.61 +/- 8.91. All of the tender point evaluation methods correlated positively with each other (P < 0.01). Fibromyalgia impact questionnaire score was also correlated with only digital palpation tender point count of these three evaluation methods (r = 0.427, P < 0.05). Digital tender point count seemed to be sufficient for assessment, and there is no need for an additional instrument for tender point evaluation.

Adult↗
PubMed1997

Fibromyalgia as a disorder of perceptual organization? An analysis of acoustic stimulus processing in patients with widespread pain.

We examined to what extent patients with fibromyalgia differ from painfree control subjects in the perception and processing not only of somatosensory but also of external stimuli. For this purpose the acoustic perception of 30 patients with fibromyalgia was compared with that of 36 generally pain-free age and gender matched subjects. The groups were also controlled for organic disease of pathological dysfunction of the ear and auditory nerves. Thresholds of unpleasantness and hearing thresholds were determined autiometrically for various frequencies. In addition the participants rated their experience of daily noise, vulnerability to acoustic stress, and functional and affective complaints associated with fibromyalgia. As expected the results show reduced unpleasantness thresholds for all frequencies and a nonsymptomatic hearing loss for higher frequencies. The elevated hearing threshold correlated significantly with experience of noise at the place of work, which was also elevated in the fibromyalgia group. Generalized pain had a high impact on the interaction between threshold of unpleasantness and daily noise experience. We interpret the differences in thresholds of hearing and of unpleasantness in patients with fibromyalgia as a form of either preconscious or conscious acts to protect against disturbing stimulation. Our results support the notion of a generalized disturbancy of perceptual thresholds in patients with fibromyalgia not restricted to the perception of pain.

Adult↗
PubMed2002

Peripheral and central sensitization in fibromyalgia: pathogenetic role.

Characteristic symptoms of fibromyalgia syndrome include widespread pain, fatigue, sleep abnormalities, and distress. Patients with fibromyalgia show psychophysical evidence of mechanical, thermal, and electrical hyperalgesia. Peripheral and central abnormalities of nociception have been described in fibromyalgia. Important nociceptor systems in the skin and muscles seem to undergo profound changes in patients with fibromyalgia through unknown mechanisms. They include sensitization of vanilloid receptor, acid-sensing ion channel receptors, and purino-receptors. Tissue mediators of inflammation and nerve growth factors can excite these receptors and cause extensive changes in pain sensitivity, but patients with fibromyalgia lack consistent evidence for inflammatory soft tissue abnormalities. Therefore, recent investigations have focused on central nervous system mechanisms of pain in fibromyalgia.

Brain↗
PubMed2003

Fibromyalgia, hepatitis C infection, and the cytokine connection.

Fibromyalgia and chronic hepatitis C infection share many clinical features including prominent somatic complaints such as musculoskeletal pain and fatigue. There is a growing body of evidence supporting a link between cytokines and somatic complaints. This review discusses alterations of cytokines in fibromyalgia, including increased serum levels of interleukin (IL)-2, IL-2 receptor, IL-8, IL-1 receptor antagonist; increased IL-1 and IL-6 produced by stimulated peripheral blood mononuclear cell in patients with FM for longer than 2 years; increased gp130, which is a neutrophil cytokine transducing protein; increased soluble IL-6 receptor and soluble IL-1 receptor antagonist only in patients with fibromyalgia who are depressed; and IL-1 beta, IL-6, and TNF-a by reverse transcriptase-polymerase chain reaction in skin biopsies of some patients with fibromyalgia. In addition, this review describes the mechanism by which alterations in cytokines in fibromyalgia and chronic hepatitis C infection can produce hyperalgesia and other neurally mediated symptoms through the presence of cytokine receptors on glial cells and opiate receptors on lymphocytes and the influence of cytokines on the hypothalamus-pituitary-adrenal axis such as IL-1, IL-6, and TNF-a activating and IL-2 and IFN-a down-regulating the HPA axis, respectively. The association between chronic hepatitis C infection and fibromyalgia is discussed, including a description of key cytokine changes in chronic hepatitis C infection. Future studies are encouraged to further characterize these immunologic alterations with potential pathophysiologic and therapeutic implications.

Antigens, CD↗
PubMed2005

Predictors of clinical pain intensity in patients with fibromyalgia syndrome.

Central changes in pain processing have been previously reported in patients with fibromyalgia syndrome. These changes include decreased thresholds to mechanical and thermal stimuli (allodynia) and central sensitization, both of which are fundamental to the generation of clinical pain. Therefore, psychophysical measures of central pain processing may be useful predictors of clinical pain intensity of fibromyalgia syndrome patients. Previous studies of fibromyalgia syndrome patients have shown statistically significant correlations of psychophysical test results with clinical pain intensity. The tests used to characterize this important relationship were dependent on spinal cord pain mechanisms and included temporal summation of pain or wind-up and wind-up after-sensations. Particularly, the magnitude of wind-up after-sensations appeared to be one of the best predictors for clinical pain intensity of fibromyalgia syndrome patients (27%). Furthermore, the combination of tender point count, negative affect, and wind-up after-sensations accounted for approximately 50% of the variance in clinical pain intensity of fibromyalgia syndrome patients. Therefore, wind-up after-sensations, tender point count, and negative affect not only seem to represent relevant pain mechanisms but also strongly emphasize their importance for fibromyalgia syndrome pain.

Fibromyalgia↗
PubMed2004

Predictors of clinical pain intensity in patients with fibromyalgia syndrome.

Central changes in pain processing have been previously reported in patients with fibromyalgia syndrome. These changes include decreased thresholds to mechanical and thermal stimuli (allodynia) and central sensitization, both of which are fundamental to the generation of clinical pain. Therefore, psychophysical measures of central pain processing may be useful predictors of clinical pain intensity of fibromyalgia syndrome patients. Previous studies of fibromyalgia syndrome patients have shown statistically significant correlations of psychophysical test results with clinical pain intensity. The tests used to characterize this important relationship were dependent on spinal cord pain mechanisms and included temporal summation of pain or wind-up and wind-up after-sensations. Particularly, the magnitude of wind-up after-sensations appeared to be one of the best predictors for clinical pain intensity of fibromyalgia syndrome patients (27%). Furthermore, the combination of tender point count, negative affect, and wind-up after-sensations accounted for approximately 50% of the variance in clinical pain intensity of fibromyalgia syndrome patients. Therefore, wind-up after-sensations, tender point count, and negative affect not only seem to represent relevant pain mechanisms but also strongly emphasize their importance for fibromyalgia syndrome pain.

Fibromyalgia↗
PubMed1981

Primary fibromyalgia (fibrositis): clinical study of 50 patients with matched normal controls.

Detailed clinical study of 50 patients with primary fibromyalgia and 50 normal matched controls has shown a characteristic syndrome. Primary fibromyalgia patients are usually females, aged 25-40 yr, who complain of diffuse musculoskeletal aches, pains or stiffness associated with tiredness, anxiety, poor sleep, headaches, irritable bowel syndrome, subjective swelling in the articular and periarticular areas and numbness. Physical examination is characterized by presence of multiple tender points at specific sites and absence of joint swelling. Symptoms are influenced by weather and activities, as well as by time of day(worse in the morning and the evening). In contrast, symptoms of psychogenic rheumatism patients have little fluctuation, if any, and are modulated by emotional rather than physical factors. In psychogenic rheumatism, there is diffuse tenderness rather than tender points at specific sites. Laboratory tests and roentgenologic findings in primary fibromyalgia are normal or negative. Primary fibromyalgia should be suspected by the presence of its own characteristic features, and not diagnosed just by the absence of other recognizable conditions. This study has also shown that primary fibromyalgia is a poorly recognized condition. Patients were usually seen by many physicians who failed to provide a definite diagnosis despite frequent unnecessary investigations. A guideline for diagnosis of primary fibromyalgia, based upon our observations, is suggested. Management is usually gratifying in these frustrated patients. The most important aspects are a definite diagnosis, explanation of the various possible mechanisms responsible for the symptoms, and reassurance regarding the benign nature of this condition. A combination of reassurance, nonsteroidal antiinflammatory drugs, good sleep, local tender point injections, and various modes of physical therapy is successful in most cases.

Adolescent↗
PubMed1993

The impact of a meditation-based stress reduction program on fibromyalgia.

Fibromyalgia is a chronic illness characterized by widespread pain, fatigue, sleep disturbance, and resistance to treatment. The purpose of this study was to evaluate the effectiveness of a meditation-based stress reduction program on fibromyalgia. Seventy-seven patients meeting the 1990 criteria of the American College of Rheumatology for fibromyalgia took part in a 10-week group outpatient program. Therapists followed a carefully defined treatment approach and met weekly to further promote uniformity. Patients were evaluated before and after the program. Initial evaluation included a psychiatric structured clinical interview (SCID). Outcome measures included visual analog scales to measure global well-being, pain, sleep, fatigue, and feeling refreshed in the morning. Patients also completed a medical symptom checklist, SCL-90-R, Coping Strategies Questionnaire, Fibromyalgia Impact Questionnaire, and the Fibromyalgia Attitude Index. Although the mean scores of all the patients completing the program showed improvement, 51% showed moderate to marked improvement and only they were counted as "responders." These preliminary findings suggest that a meditation-based stress reduction program is effective for patients with fibromyalgia.

Adaptation, Psychological↗
PubMed1988

Tender points in fibromyalgia.

To establish inter-rater and test-retest reliability of use of a pressure algometer, 5 males and 5 females suffering from chronic fibromyalgia ('fibrositis'), and a normal group of 5 males and 5 females, were examined 2 times by each of 2 independent examiners, using 1 kg/sec rate of application, over 10 paired and typical 'tender points,' localized by skin marker. Tenderness thresholds of tender points were coded and analyzed using repeated measures ANOVA, for factors sex, normal/fibromyalgia, and side, rater, and time 1/time 2. There was significantly lower tenderness thresholds of tender points in fibromyalgia compared to normal subjects. Generalizability coefficients were calculated and showed high inter-rater (0.85), and test-retest (0.85) reliability. Highly significant differences were found between specific tender points. A further 10 normals and 10 fibromyalgia subjects were then examined for 5 paired tender points and 5 paired non-tender points. A 2-way ANOVA was conducted for summed and averaged scores for all tender and non-tender points, with factors normal/fibromyalgia and tender/non-tender; again, there was a large difference between normal and fibromyalgia subjects, and between tender and non-tender points. The interaction was small but significant, but there was a larger difference between fibromyalgia and normal subjects observed on non-tender points. The low tenderness threshold observed at the tender points of fibromyalgia patients may reflect a more generalized lowering of tenderness thresholds, seen at non-tender points as well.

Female↗
PubMed1996

Generalized hypervigilance in fibromyalgia: evidence of perceptual amplification.

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.

Adult↗
PubMed2005

The effects of a 12-week strength-training program on strength and functionality in women with fibromyalgia.

OBJECTIVE: To determine whether women with fibromyalgia benefit from strength training. DESIGN: Randomized controlled trial. SETTING: Testing was completed at the university and training was completed at a local community wellness facility. PARTICIPANTS: Twenty-nine women (age range, 18-54 y) with fibromyalgia participated. Subjects were randomly assigned to a control (n=14; wait-listed for exercise) or strength (n=15) group. After the first 4 weeks, 7 (47%) women dropped from the strength group. INTERVENTION: Subjects underwent 12 weeks of training on 11 exercises, 2 times a week, performing 1 set of 8 to 12 repetitions at 40% to 60% of their maximal lifts and were progressed to 60% to 80%. MAIN OUTCOME MEASURES: Subjects were measured for strength, functionality, tender point sensitivity, and fibromyalgia impact. RESULTS: The strength group significantly (P< or =.05) improved upper- (strength, 39+/-11 to 42+/-12 kg; control, 38+/-13 to 38+/-12 kg) and lower- (strength, 68+/-28 to 82+/-25 kg; control, 61+/-25 to 61+/-26 kg) body strength. Upper-body functionality measured by the Continuous-Scale Physical Functional Performance test improved significantly (strength, 44+/-11 to 50+/-16U; control, 51+/-11 to 49+/-13U) after training. Tender point sensitivity and fibromyalgia impact did not change. CONCLUSIONS: Strength training improved strength and some functionality in women with fibromyalgia. Interventions with resistance have important implications on independence and quality of life issues for women with fibromyalgia.

Activities of Daily Living↗
PubMed2004

Electroconvulsive therapy in patients with depression and fibromyalgia.

The effect of electroconvulsive therapy (ECT) on depression and other symptoms of fibromyalgia was studied in a prospective 3-month trial in 13 patients with fibromyalgia and concomitant depression. All the patients met the DSM-IV diagnostic criteria for Major Depressive Disorder and fulfilled the American College of Rheumatology diagnostic criteria for fibromyalgia. The Montgomery and Asberg Depression Rating Scale (MADRS) and the clinical global impression scale (CGI) were used to assess the severity of depression and the clinical change of the patients. The fibromyalgia impact questionnaire (FIQ) was used to evaluate the severity of the fibromyalgia symptoms. The intensity of pain was evaluated using a 6-point scale (0=no pain, 5=very severe pain), and tender point palpation. All assessments were performed at baseline and at follow-up visits, which took place one week, one month and three months after ECT. There was a significant improvement in depression after ECT according to MADRS. Using CGI, six patients were much or very much improved, while four patients were minimally improved and three patients had no change. There was significant improvement in four out of ten FIQ item scores, "feel good", "fatigue", "anxiety" and "depression". No significant change was found in the FIQ item scores "physical function", "pain", "stiffness" and "morning tiredness" or number of tender points and self-reported pain. We conclude that ECT is a safe and effective treatment for depression in fibromyalgia patients, but has no effect on the pain or other physical symptoms of these patients.

Adult↗
PubMed2006

A reconsideration of the relevance of systemic low-dose ketamine to the pathophysiology of fibromyalgia.

UNLABELLED: Fibromyalgia is a common disorder characterized by chronic widespread pain that affects an estimated 2% of the general population. Recent advances have shed insight on this mysterious disorder, leading to the growing conclusion that disturbances of pain-related processes within the central nervous system, termed central sensitization, represent its most likely source. The phenomenon of central sensitization depends on plasticity in function of N-methyl-D-aspartate (NMDA) subtype glutamate receptors. Earlier studies implicated increased sensitivity of central NMDA receptors as playing a primary role in fibromyalgia, as evidenced by a significant reduction in symptoms among a large subset of patients in response to low doses of ketamine, a noncompetitive NMDA receptor antagonist. However, recent insights into the pharmacology of this drug cast doubt on a direct contribution of NMDA receptors and add credence to a model of the disorder that suggests that the primary pathology of fibromyalgia is a suppression of the normal activity of dopamine-releasing neurons within the limbic system. The implications for future therapies for fibromyalgia, and indeed many other chronic pain conditions, are discussed in light of these insights. PERSPECTIVE: The current lack of a demonstrable pathology underlying the pain of fibromyalgia has hampered progress toward adequate treatment of this mysterious disorder. Accumulating evidence suggests that fibromyalgia may represent a dysregulation of dopaminergic neurotransmission, which may provide insights to guide both rational clinical interventions as well as system-specific research models.

Dopamine↗