Fibromyalgia: Späth M

Carville SF, Arendt-Nielsen S, Bliddal H, Blotman F, Branco JC, Buskila D, Da Silva JA, Danneskiold-Samsøe B, Dincer F, Henriksson C, Henriksson KG, Kosek E, Longley K, McCarthy GM, Perrot S, Puszczewicz M, Sarzi-Puttini P, Silman A, Späth M, Choy EH, Anonymous00148. · Academic Rheumatology Unit, King's College London, Weston Education Centre, Cutcombe Road, London SE5 9RJ, UK. · Ann Rheum Dis. · Pubmed #17644548 No free full text.

Abstract: OBJECTIVE: To develop evidence-based recommendations for the management of fibromyalgia syndrome. METHODS: A multidisciplinary task force was formed representing 11 European countries. The design of the study, including search strategy, participants, interventions, outcome measures, data collection and analytical method, was defined at the outset. A systematic review was undertaken with the keywords "fibromyalgia", "treatment or management" and "trial". Studies were excluded if they did not utilise the American College of Rheumatology classification criteria, were not clinical trials, or included patients with chronic fatigue syndrome or myalgic encephalomyelitis. Primary outcome measures were change in pain assessed by visual analogue scale and fibromyalgia impact questionnaire. The quality of the studies was categorised based on randomisation, blinding and allocation concealment. Only the highest quality studies were used to base recommendations on. When there was insufficient evidence from the literature, a Delphi process was used to provide basis for recommendation. RESULTS: 146 studies were eligible for the review. 39 pharmacological intervention studies and 59 non-pharmacological were included in the final recommendation summary tables once those of a lower quality or with insufficient data were separated. The categories of treatment identified were antidepressants, analgesics, and "other pharmacological" and exercise, cognitive behavioural therapy, education, dietary interventions and "other non-pharmacological". In many studies sample size was small and the quality of the study was insufficient for strong recommendations to be made. CONCLUSIONS: Nine recommendations for the management of fibromyalgia syndrome were developed using a systematic review and expert consensus.

Späth M, Stratz T, Färber L, Haus U, Pongratz D. · Friedrich-Baur-Institute, University of Munich, Munich, Germany. · Scand J Rheumatol Suppl. · Pubmed #15515418 No free full text.

Abstract: Previous studies evaluating the efficacy and tolerance of tropisetron for the treatment of fibromyalgia (FM) used the drug either intravenously or orally, and at different dosage levels ranging from 2 mg to 15 mg daily. The shortest treatment was a single dose and the longest treatment period covered 28 days. A significant reduction of the pain intensity was achieved by using tropisetron 5 mg per day. Apart from the fact that treatment periods were different, the efficacy of oral and intravenous administration did not differ significantly. Tropisetron was well tolerated; but in the 15 mg group in one of the studies, the decrease in pain was less than in the placebo group, however, the frequency of constipation and other gastrointestinal symptoms increased. Furthermore, it was hypothesized that due to the impacts of CYP2D6 activities, a daily dose of tropisetron 2 mg may be efficacious in slow metabolizers only. Although tropisetron proved to be efficacious in a group of fibromyalgia patients, the dose-response curves cannot yet be explained in a fully satisfactory manner, which may encourage research focusing on possible subgroups of FM.

Haus U, Späth M, Färber L. · Novartis Pharma GmbH, Nuremberg, Germany. · Scand J Rheumatol Suppl. · Pubmed #15515406 No free full text.

Abstract: Several 5-HT3 receptor antagonists are available (tropisetron, ondansetron, granisetron, dolasetron, and palonsetron), and further compounds are in clinical development. These substances show only minor differences in the activity profile regarding their affinity for particular receptors. 5-HT3 receptor antagonists are primarily used and found effective in the prevention and treatment of chemotherapy-induced nausea and emesis, and in postoperative nausea and vomiting (PONV). Antagonism of the 5-HT3 receptors in the peripheral and central nervous system is a probable mechanism of action. The substances are suitable as first-line therapy (combined with a corticosteroid) for the prevention of acute nausea and vomiting in patients treated with moderately to severely emetogenic chemotherapeutic agents. This combination is also moderately effective in the prevention of delayed nausea and vomiting. 5-HT3 receptor antagonists are an important constituent in the prevention and treatment of emesis and nausea caused by radiation therapy, especially in patients receiving whole body or upper abdominal treatment. Alosetron was found clinically effective in diarrhoea-predominant irritable bowel syndrome, whereas tropisetron in fibromyalgia and related pain disorders. Further indications for such treatment include anxiety disorders, alcohol dependence, drug withdrawal, and psychosis related to treatment of Parkinson's disease. 5-HT3 receptor antagonists are well tolerated with the most frequently reported adverse effects being headache, constipation, dizziness, tiredness, and gastrointestinal disturbances such as abdominal pain or constipation. Intravenous administration of serotonin induces the Bezold-Jarisch reflex and causes small reversible changes in electrocardiogram (ECG) parameters.

Färber L, Haus U, Späth M, Drechsler S. · Department of Pharmacology, Regensburg Medical School, Regensburg, Germany. · Scand J Rheumatol Suppl. · Pubmed #15515404 No free full text.

Abstract: The 5-HT3 receptor is a ligand-gated cation channel located in the central and peripheral nervous system; it has also been detected on a variety of other cells. In the periphery, it is found on autonomic neurons and on neurons of the sensory and enteric nervous system. In the CNS, the 5-HT3 receptor has been localized in the area postrema, nucleus tractus solitarii, nucleus vaudatus, nucleus accumbens, amygdala, hippocampus, entorhinal, frontal, cingulate cortex, and in the dorsal horn ganglia. Further extraneuronal locations include among others lymphocytes, monocytes, and foetal tissue. 5-HT3 receptors modulate the release of neurotransmitters and neuropeptides like dopamine, cholecystokinin, acetylcholine, GABA, substance P, and serotonin itself. They have been demonstrated to be involved in sensory transmission, regulation of autonomic functions, integration of the vomiting reflex, pain processing and control of anxiety. While the physiologic functions of the 5-HT3 receptor are discrete and difficult to detect, it plays a key role in certain pathologic situations related to increased serotonin release. Clinical development of 5-HT3 receptor antagonists revealed a remarkable range of activities. 5-HT3 receptor antagonists do not modify any aspect of normal behaviour in animals or induce pronounced changes of physiological functions in healthy subjects. Clinical efficacy was shown for various forms of emesis like chemotherapy-induced, radiotherapy-induced, and postoperative emesis, diarrhoea-predominant irritable bowel syndrome, anxiety, chronic fatigue syndrome, alcohol abuse, and in pain syndromes such as fibromyalgia and migraine. Most recent data also suggest that 5-HT3 receptor antagonists are effective for the treatment of other rheumatic diseases such as rheumatoid arthritis, tendinopathies, periarthropathies, and myofascial pain. Other possible indications under discussion are chronic heart pain and bulimia. Unfortunately, experimental findings do not yet provide a homogenous conception of the significance of 5-HT3 receptors in all investigated fields; in nociception, for example, contradictory observations are still inadequately explained and complicated by bell-shaped dose-response curves. Further elucidation and better understanding of the serotonergic neuronal network remains a task for the next decade.

Späth M. · Friedrich-Baur-Institut, Ludwig-Maximilians-Universität München. · Schmerz. · Pubmed #14648317 No free full text.

Abstract: Modern management of fibromyalgia (FM) requires a holistic approach, which includes nonpharmacologic strategies (both exercise and behavioral strategies) and pharmacologic treatment. Despite only partial effects in some patients, tricyclic antidepressants, selective serotonin reuptake inhibitors, nonsteroidal antiinflammatory drugs, analgesics and opioids are in use. The use of antiepileptic drugs and antispasticity agents is mainly supported by anecdotal data. Three other classes of agents are currently thought to have useful potentials. N-methyl-D-aspartate-(NMDA-)mediated neurotransmission may play an important role in mediating wind-up and related phenomena in pain pathways. Recent studies have demonstrated that NMDA receptor antagonists improve pain symptoms in FM. But a poor side effect profile represents a significant problem. Cerebrospinal fluid substance P concentrations are significantly elevated in FM patients, but the analgesic potential of neurokinin-1 (NK1) receptor antagonists did not meet early expectations. Tropisetron, a 5-HT3 receptor antagonist, was tested in a multicenter, double-blind, randomized, placebo-controlled trial including 403 patients. In those receiving 5 mg tropisetron, 39.2% fulfilled the response criterion (pain reduction 35%) as compared to 26.2% in the placebo group (p=0.033). On 10 and 15 mg, the responder rates were smaller and statistically not significant. A total of 78 responders to therapy were followed up for 12 months. After the end of treatment, pain intensity rose within one month in all 4 groups. Patients having received 5 or 10 mg showed a less pronounced increase in pain. In addition, even 12 months after stopping treatment, pain was still markedly below baseline levels in the 5 and 10 mg groups.

Späth M. · Friedrich-Baur-Institute, Ludwig-Maximilians-University, Ziemssenstr. 1L D-80336, München, Germany. · Rheum Dis Clin North Am. · Pubmed #12122920 No free full text.

Abstract: Pain is perceived, transmitted, processed and modulated within an extensive network of neurotransmitters and hormones. Despite increasing knowledge about the biologic principles, even on the molecular level, the more we learn about the precise mechanisms of their interactions the more questions arise. It is also pertinent to remember that clinical scientists studying pain modulating pharmacologic agents always have to consider possible placebo effects [57-61]. Most of our knowledge regarding the function of neurotransmitter systems in the CNS has been provided by animal studies. Thus we cannot be sure that they have exactly parallel counterparts in humans. For instance, animal studies suggest an inverse relationship between brain and spinal cord concentrations of substance P. If these observations are converted to an interpretation of human fibromyalgia, low brain-tissue levels of both serotonin and substance P should be expected, while spinal cord serotonin concentrations would be low and spinal cord substance P would be high [1]. There is good evidence that 5-HT, its receptors, and their interactions with other neurotransmitters are essential for nociception and antinociception. The activities of 5-HT receptors can be studied by agonist and in humans especially by antagonist use. But even with a direct spinal application of selective agonists and antagonists, observations may still be confounded by (1) dose, as there can be a dose-dependent activation of different receptor subtypes; (2) type of nociceptive tests (e.g., thermal versus pressure versus chemical models), which may have differences in the way they are regulated; and (3) influences due to effects on temperature, blood flow or motor function. With this potential for variability, it is perhaps not surprising that there is some variability in the results of studies reporting on the effects of various 5-HT agonists and antagonists on nociceptive transmission within the spinal cord [62]. For instance, different 5-HT3 receptor densities could exist in various neuronal systems, one density type being completely inhibited at low concentrations, and the others only at higher concentrations of 5-HT3 receptor antagonists, thus resulting in contrary effects. Finally, the "endogeneous 5-HT tone" may greatly influence agonist and antagonist action. Considering this complexity of serotonin-mediated reactions, it is not surprising that treatment of pain by 5-HT3 receptor antagonists appears to yield inconsistent results. As fibromyalgia is now regarded as a pain amplification syndrome with a broad variety of additional nonpain symptoms, the interrelations are complicated even more. Fibromyalgia associated symptoms (e.g., fatigue, insomnia, and irritable bowel syndrome) can be modulated by 5-HT3 receptor antagonists. From the data evaluated so far, there is evidence that 5-HT3 receptor antagonists provide significant benefit in some fibromyalgia patients. In our practice, the data justify a careful application in clinical use according to the study results. The dosage, route of application, long term adverse reactions and duration of therapy still need to be studied in greater detail. Recently reported adverse events from therapy of irritable bowel syndrome with alosetron [63-67] provide a note for caution before hastily using 5-HT3 receptor antagonists without more studies. One can surmise that, much as the biochemistry of depression has been elucidated by the development of the SSRIs, a greater understanding of the role of 5-HT3 receptor antagonists in treating fibromyalgia patients may provide some insights into disease mechanisms of this enigmatic disorder.

Pongratz D, Späth M. · Friedrich-Baur-Institut, Medizinische und Neurologische Klinik, Klinikum der Universität, Innenstadt, München. · Fortschr Neurol Psychiatr. · Pubmed #11386124 No free full text.

Abstract: The classification of fibromyalgia is based on the criteria of the American College of Rheumatology. For diagnostic reasons autonomic disturbances and mental features have to be considered. The distinction between fibromyalgia (tender points) and myofascial pain syndrome (trigger points) is essential. Internal and neurological disorders as a primary cause of fibromyalgia have to be excluded. The aetiology and pathogenesis of fibromyalgia still remain uncertain. The myopathological patterns in fibromyalgia are non-specific: type-II-fiber-atrophy, a slight increase in lipid droplets, a proliferation of mitochondria and a slightly elevated incidence of ragged red fibers. Biochemically alterations of the serotonin system and high levels of substance P in the cerebrospinal fluid of fibromyalgia patients are important. Animal experiments showed that the central stimulation by nociceptor input from muscles is exaggerated in skeletal muscle pain conditions, suggesting central hyperexcitability. The diagnosis of fibromyalgia requires a thorough exclusion of other rheumatologic and neurologic disorders. The differential diagnosis is complicated by an overlap to other chronic somatoform pain disorders.

Späth M, Stratz T, Neeck G, Kötter I, Hammel B, Amberger CC, Haus U, Färber L, Pongratz D, Müller W. · Friedrich-Baur-Institute, University of Munich, D-80336 München, Germany. · Scand J Rheumatol. · Pubmed #15370724 No free full text.

Abstract: OBJECTIVE: To determine the efficacy of a serotonin receptor (5-HT(3)) antagonist in the treatment of fibromyalgia (FM) in a prospective, randomized, double-blind, placebo-controlled, multicentre trial. METHODS: Twenty-one female patients (age 21-63 years) with FM according to the American College of Rheumatology classification criteria for FM were assigned randomly to either a placebo group or to receive a daily intravenous bolus injection of 5 mg tropisetron for 5 days. RESULTS: In patients receiving tropisetron, the visual analogue scale (VAS) score for pain decreased by 28.9 compared with a decrease of 6.8 in the placebo group [probability (p)=0.063; effect size: 0.794]. Similar results were obtained using a body diagram pain score as a secondary efficacy parameter: mean pain reduction was 27.2 in the tropisetron group, versus 2.8 in the placebo group (p=0.038; effect size: 0.902). CONCLUSION: 5-HT(3) receptor antagonists provide significant pain relief for a group of FM patients.

Färber L, Stratz TH, Brückle W, Späth M, Pongratz D, Lautenschläger J, Kötter I, Zöller B, Peter HH, Neeck G, Welzel D, Müller W, Anonymous00012. · Institut für Pharmakologie der Universität Regensburg, Germany. · Int J Clin Pharmacol Res. · Pubmed #11708570 No free full text.

Abstract: We investigated the efficacy and tolerability of short-term treatment with tropisetron, a selective, competitive 5-HT3-receptor antagonist in fibromyalgia. The trial was designed as a prospective, multicenter, double-blind, parallel-group, dose-finding study. We randomly assigned 418 patients suffering from primary fibromyalgia to receive either placebo, 5 mg, 10 mg or 15 mg tropisetron once daily for 10 days. Clinical response was measured by changes in pain score, visual analog scale, tender point count and ancillary symptoms. Responders were prospectively defined as patients showing a 35% or higher reduction in pain score. Treatment with 5 mg tropisetron resulted in a significantly higher response rate (39.2%) than placebo (26.2%) (p < 0.05). In the visual analog scale, the group administered 5 mg tropisetron showed a significant improvement (p < 0.05) and the group administered 10 mg tropisetron showed a nonsignificant clinical benefit. The number of painful tender points was significantly reduced (p = 0.002) in the 5 mg tropisetron group. Regarding ancillary symptoms, the 5 mg tropisetron group showed a significant improvement (p < 0.05) in sleep and dizziness. The patients' overall assessment of efficacy was significantly higher for 5 mg (p = 0.016) and 10 mg (p = 0.002) tropisetron than for placebo. The safety and tolerability of tropisetron was good; gastrointestinal tract symptoms were the most frequently reported adverse events. Short-term treatment of fibromyalgia patients with 5 mg tropisetron for 10 days proved to be efficacious and well tolerated. In this study a bell-shaped dose-response curve was seen.

Haus U, Varga B, Stratz T, Späth M, Müller W. · Novartis Pharma GmbH, Department of Clinical Research, Nürnberg, Germany. · Scand J Rheumatol Suppl. · Pubmed #11028833 No free full text.

Abstract: The 5-HT3 receptor antagonists are a novel therapy for patients suffering from fibromyalgia, although the optimal duration of treatment is still unclear. The objective of this phase II study was to evaluate whether prolonging treatment with tropisetron to 4 weeks is tolerable and correlated with an improved clinical benefit. Thirty female patients with fibromyalgia received oral tropisetron (5 mg) daily for 28 days in an open-label fashion. Treatment resulted in significantly decreased pain as measured by visual analog scale (VAS), with a mean reduction of 59.7% and an absolute median change of -25.0 from baseline to day 28 (p<0.0001). A similar, significant reduction of 55.7% and absolute median change of -31.0 was observed in the painscore (p<0.0001). The response rate with patients showing a > or = 35% reduction in individual pain scores was 72.4% at day 28. The pressure tolerance of tender-points was slightly increased at the end of the treatment period. In addition, significant improvements were observed in the State-Trait-Anxiety-Inventory (STAI), scales of von Zerssen (Bf-S) and Beck Depression Index (BDI). Functional symptoms were compared with the results from a 10-day, randomized, double-blind phase III study of tropisetron in 418 fibromyalgia patients. In both studies several functional symptoms such as sleep disturbances and dizziness improved significantly (p<0.05). In the 28 days study, the number and extent of improvement in functional symptoms was increased compared with the shorter trial. Tolerability and safety of tropisetron was good, and typically for 5-HT3-receptor antagonists, gastrointestinal symptoms and headache were the most frequently reported events. In conclusion, 28 days treatment of fibromyalgia patients with 5 mg tropisetron resulted in significant pain reduction, which was most pronounced after 10 days with a further reduction up to day 28. Psychometric tests showed significant improvements in depression and anxiety state scores, while functional symptoms improved with extended tropisetron treatment.

Färber L, Stratz T, Brückle W, Späth M, Pongratz D, Lautenschläger J, Kötter I, Zöller B, Peter HH, Neeck G, Alten R, Müller W. · Institut für Pharmakologie der Universität Regensburg, Germany. · Scand J Rheumatol Suppl. · Pubmed #11028832 No free full text.

Abstract: OBJECTIVE: Based on a potential role for serotonin receptors in fibromyalgia, we investigated the efficacy and tolerability of treatment with tropisetron, a highly selective, competitive inhibitor of the 5-HT3 receptor. METHODS: In this prospective, multicenter, double-blind, parallel-group, dose-finding study, 418 patients suffering from primary fibromyalgia (ACR criteria) were randomly assigned to receive either placebo, 5 mg, 10 mg or 15 mg tropisetron once daily, respectively. The duration of treatment was 10 days. The clinical response was measured by changes in pain-score, visual analog scale (VAS), and the number of painful tender-points. RESULTS: Treatment with 5 mg tropisetron resulted in a significantly higher response rate (39.2%) when compared with placebo (26.2%) (p=0.033). The absolute reduction in pain-score was -13.5% for 5 mg tropisetron, -13.0% for 10 mg tropisetron, and -6.3% for placebo (p<0.05). The effects of 15 mg tropisetron were similar to placebo, thus suggesting a bell-shaped dose-response curve. Compared with placebo, treatment with 5 mg tropisetron led to a significant improvement (p<0.05) in VAS, while a clear trend in terms of clinical benefit was seen with 10 mg tropisetron. The number of painful tender-points was also reduced significantly (p=0.002) in the 5 mg tropisetron group. Of interest, during the 12-month follow-up period, pain intensity of responders on 5 mg and 10 mg tropisetron was still markedly below baseline. The treatment was well tolerated, with gastro-intestinal complaints being the most frequently reported side effects, in keeping with the known safety profile for 5-HT3 receptor antagonists. CONCLUSIONS: This study demonstrates the efficacy of short-term treatment with 5 mg tropisetron once daily in primary fibromyalgia. Treatment was well tolerated and prolonged clinical benefits were seen.

Rüster M, Franke S, Späth M, Pongratz DE, Stein G, Hein GE. · Department of Internal Medicine III, Friedrich-Schiller-University of Jena, Germany. · Scand J Rheumatol. · Pubmed #16393769 No free full text.

Abstract: OBJECTIVES: To compare levels of the advanced glycation end product (AGE) N(epsilon)-carboxymethyllysine (CML) present in the muscle tissue and in the serum of patients with fibromyalgia (FM) vs. healthy controls. METHODS: The serum levels of CML were measured in 41 patients with FM and 81 healthy controls. The presence of CML, nuclear factor kappa B (NF-kappaB), the AGE receptor (RAGE), collagen types I, II, VI, and CD68-positive monocytes/macrophages in muscle tissue of 14 patients with FM was investigated by immunohistochemistry. RESULTS: Patients with FM showed significantly increased serum levels of CML in comparison to healthy controls. The immunohistochemical investigation revealed a stronger staining for CML and NF-kappaB and more CD68-positive monocytes/macrophages in the muscle of FM patients. The collagens and CML were co-localized, suggesting that the AGE modifications were related to collagen. RAGE was absent in controls but a faint and patchy staining was seen in FM. CONCLUSIONS: In the interstitial connective tissue of fibromyalgic muscles we found a more intensive staining of the AGE CML, activated NF-kappaB, and also higher CML levels in the serum of these patients compared to the controls. RAGE was only present in FM muscle. AGE modification of proteins causes reduced solubility and high resistance to proteolytic digestion of the altered proteins (e.g. AGE-modified collagens). AGEs can stimulate different types of cells by activation of the transcription factor NF-kappaB, mediated by specific receptors of AGEs (e.g. RAGE) on the cell surface. Both mechanisms may contribute to the development, perpetuation, and spreading of pain characteristic in FM patients.

Kohnen R, Färber L, Späth M. · IMEREM Institute for Medical Research Management and Biometrics Ltd., Germany. · Scand J Rheumatol Suppl. · Pubmed #15515419 No free full text.

Abstract: Vegetative and functional symptoms are, besides pain and tenderness of tender points, considered as additional information for the diagnosis of fibromyalgia (FM). In clinical trials, vegetative and functional symptoms have been included for selection of patients (e.g. sleep disturbances) and as secondary outcome parameters. Despite the relevance of these symptoms, no validated method is currently available but symptom lists are ad hoc developed by investigators. In this manuscript, data from a published double blind, randomised study are reanalysed which compared oral therapy over 10 days with 5 mg, 10 mg, and 15 mg to placebo in FM patients. This study applied a list of 17 vegetative and functional symptoms, which had to be scored by the patients by use of a 4-point severity scale (0 = none to 3 = severe). Factor analysis of the baseline data from 195 patients suggested to separate 6 sub-scales: Cardiovascular, gastrointestinal, psychiatric (sleep disturbance), nervous, autonomic system, and general disorders. Sleep disturbances, general symptoms (morning stiffness, fatigue) and autonomic symptoms (cold extremities, hyperhidrosis) were most severe in intensity. Analysis of sensitivity for treatment effects made use of differences between placebo and 5 mg tropisetron in changes between baseline and final assessment of the tropisetron trial. While, on the item level, differences in favour of tropisetron could only be demonstrated for sleep disorders, on the sub-scale level, also favourable effects of tropisetron could be shown for cardiovascular and nervous system complaints and, as a tendency, for general symptoms. On the other side, the sub-scale score of gastrointestinal symptoms worsened under tropisetron whilst it improved under placebo which effect was due to side effects of the active treatment. It is concluded that symptom clusters like sub-scales of a list of vegetative and functional symptoms will be more suitable for diagnostic purposes and evaluation of treatment outcome of clinical trials. Further research is urgently required which addresses the development of a FM-specific scale to assess vegetative and functional symptoms.

Frank B, Niesler B, Bondy B, Späth M, Pongratz DE, Ackenheil M, Fischer C, Rappold G. · Institute of Human Genetics, University of Heidelberg, Heidelberg, Germany. · Clin Rheumatol. · Pubmed #15293096 No free full text.

Abstract: The neurotransmitter serotonin (5-hydroxytryptamine, 5-HT) has been implicated in numerous human disorders. Dysfunction of serotonergic neurotransmission is thought to play a major role in the pathophysiology of the fibromyalgia syndrome (FMS) which is characterised by non-restorative sleep and severe pain. In our study, both serotonin receptor subunit genes, HTR3A and HTR3B, have been investigated for sequence variations in FMS patients in order to reveal a possible involvement in the aetiology of FMS. We examined DNA samples from 48 patients with FMS representing sporadic cases by single-strand conformation polymorphism (SSCP) and denaturing high-performance liquid chromatography (dHPLC) analysis, sequenced samples with conspicuous patterns and performed statistical calculations. HTR3A mutational analysis revealed one novel as well as five known sequence variations. Investigating HTR3B, we detected seven formerly described mutations and one novel sequence variant. Statistical computation rated all variants as probably non-disease-related polymorphisms. Nevertheless, one might speculate about an effect of the respective sequence variants on the severity of the disease. Sequence variants of the serotonin receptor subunit genes HTR3A and HTR3B indicate no obvious significance in the aetiology of fibromyalgia, yet they represent the basis for future studies on their pharmacogenetic relevance.

Späth M, Neeck G. · Friedrich-Baur-Institut, Klinikum der Ludwig-Maximilians-Universität, Ziemssenstr. 1a 80336, Munich, Germany. · Z Rheumatol. · Pubmed #12491129 No free full text.

Abstract: Research on fibromyalgia over the last ten years has focused on the broad variety of pathogenetic aspects of a pain amplification syndrome. This emphasizes pain as the leading symptom. The sociomedical implications are obvious and considerable, and therefore fibromyalgia has increasingly become the subject of expert assessments. The expert assessment should not discuss the existence or non-existence of fibromyalgia, but evaluate the individual impairments, disabilities and handicaps which may lead to an individual degree of dysfunctioning.

Müller W, Pongratz D, Bärlin E, Eich W, Färber L, Haus U, Lautenschläger J, Mense S, Neeck G, Offenbächer M, Späth M, Stratz T, Tolk J, Welzel D, Wiech K, Wohlgemuth M. · No affiliation provided · Scand J Rheumatol Suppl. · Pubmed #11028839 No free full text.

This publication has no abstract.

Schwarz MJ, Späth M, Müller-Bardorff H, Pongratz DE, Bondy B, Ackenheil M. · Psychiatric Hospital, University of Munich, Germany. · Neurosci Lett. · Pubmed #10025591 No free full text.

Abstract: The serotonergic system has repeatedly been discussed to be involved in the pathophysiology of fibromyalgia (FM), which is a syndrome of widespread pain and sleep disturbance. Elevated levels of substance P (SP), a mediator of nociception, have been described in FM. In this study the possible relationship between SP and serotonin (5-HT) together with its precursor tryptophan (TRP) and its metabolite 5-hydroxyindoleacetic acid (5-HIAA) was evaluated in 51 serum samples of fibromyalgia patients. These parameters were compared with clinical data such as pain intensity or sleep quality. A strong negative correlation between SP and 5-HIAA (P = .000) as well as between SP and TRP (P = .009) could be demonstrated. High serum concentrations of 5-HIAA and TRP showed a significant relation to low pain scores (5-HIAA: P = .030; TRP: P = .014). Moreover, 5-HIAA was strongly related to good quality of sleep (P = .000), while SP was related to sleep disturbance (P = .005). These data are valid to support the hypothesis of a systemic involvement of 5-HT and SP in fibromyalgia.