5'UTR polymorphism in the serotonergic receptor HTR3A gene is differently associated with striatal Dopamine D2/D3 receptor availability in the right putamen in Fibromyalgia patients and healthy controls-Preliminary evidence.

BACKGROUND: Extensive literature has investigated the role of serotonin (5-HT) in the control of the central dopamine (DA) systems, and their dysfunction in the pathological conditions. 5-HT stimulates the local DA release in striatal regions via activation of various receptors including serotonin receptor-3 (5-HT3). Several studies have related polymorphisms (SNPs) in the serotonin receptor-3 (HTR3) genes to be associated with the pain modulation and endogenous pain suppression. A few studies suggested a functional role of 5'UTR SNP in the serotonergic receptor HTR3A gene (rs1062613) in the development of the chronic pain and Fibromyalgia syndrome (FMS) in particular. Here, we investigated the effect of a 5'UTR SNP in the serotonergic receptor HTR3A gene (rs1062613) on striatal dopamine D2/D3 receptor (DRD2) availability and reward-associated DA release in response to unpredictable monetary rewards in 23 women with FMS and 17 age-matched healthy female controls. Furthermore, we aimed to examine if SNP rs1062613 is associated with thermal pain and pain tolerance thresholds. METHODS: We used PET and [11 C]raclopride to assess the DRD2 availability. In the same participants we used the [11 C]raclopride PET bolus-plus-infusion method to measure the [11 C]raclopride receptor binding potential (ΔBP) between an unpredictable reward condition and a sensorimotor control condition. DRD2 availability and ΔBP were assessed in MRI-based striatal regions of interest. Thermal pain and pain tolerance thresholds were assessed outside the scanner. RESULTS: The frequency of SNP rs1062613 genotype differed significantly between groups, indicating that CC homozygotes were more frequent in FMS patients (82.6%) than in healthy controls (41.3%). Our results showed a significant main effect of SNP rs1062613 on [11 C]raclopride binding potential in the right caudate nucleus indicating a higher DRD2 receptor availability for CC-genotype of this SNP. Furthermore, we found a significant group × SNP interaction on [11 C]raclopride binding potential in the right putamen, indicating a higher DRD2 availability in T-carriers compared to CC genotype of SNP rs1062613 in FMS patients, whereas this effect was not present in healthy controls. However, we did not find an influence of SNP rs1062613 on reward-related DA release. In addition, there was no association between SNP rs1062613 and pain threshold or pain tolerance threshold in our data. CONCLUSION: These preliminary results indicate that SNP rs1062613 in the serotonergic receptor HTR3A gene possibly modulates the DRD2 receptor availability.

[Drug treatment and interventional pain therapy in back pain patients]. / Medikamente und Infiltrationen bei Rückenschmerzen.

The treatment of chronic, non-malignant low-back pain is based on the patients' history and the clinical examination. It can be assumed that half of the cases present with a neuropathic pain component which needs to be treated with antidepressive and antiepileptic drugs instead of "pure" analgesics. Opioids should be considered with extreme caution because of their toxicity. Chronic non-malignant back pain is the prototype for interdisciplinary treatment approaches and multi-modal interdisciplinary settings, including pain programmes. However, a personalised strategy has to be preferred in most cases. A quick relief of pain is important in order to improve function as well as to re-integrate the patient into professional life. Spinal infiltrations can be of both diagnostic as well as therapeutic benefits. Their indication must be considered carefully, especially if the invasive diagnostic intervention has no therapeutic consequences. The interventional procedures should only be used as part of a multimodal approach in patients without any psychological problem. The sole use of interventions supports the purely somatic orientation of many patients and thus leads us in the wrong direction.

Hyaluronic Acid in Rheumatology.

Hyaluronic acid (HA), also known as hyaluronan, is an anionic glycosaminoglycan widely distributed throughout various tissues of the human body. It stands out from other glycosaminoglycans as it lacks sulfation and can attain considerable size: the average human synovial HA molecule weighs about 7 million Dalton (Da), equivalent to roughly 20,000 disaccharide monomers; although some sources report a lower range of 3-4 million Da. In recent years, HA has garnered significant attention in the field of rheumatology due to its involvement in joint lubrication, cartilage maintenance, and modulation of inflammatory and/or immune responses. This review aims to provide a comprehensive overview of HA's involvement in rheumatology, covering its physiology, pharmacology, therapeutic applications, and potential future directions for enhancing patient outcomes. Nevertheless, the use of HA therapy in rheumatology remains controversial with conflicting evidence regarding its efficacy and safety. In conclusion, HA represents a promising therapeutic option to improve joint function and alleviate inflammation and pain.

Effect of an interdisciplinary outpatient pain management program (IOPP) for chronic pain patients with and without migration background: a prospective, observational clinical study.

OBJECTIVES: Short- and long-term effects of an interdisciplinary outpatient pain program (IOPP) in terms of quality of life, coping strategies, experiencing of pain and pain intensity as well as the influence of age, gender, or migration background. DESIGN: Single, prospective cohort with assessments at baseline, posttreatment, and at 3, 6, 12 months follow-up. PATIENTS: A total of 175 patients with chronic, nonmalignant pain syndromes (32.1% male and 67.9% female; age 43 ± 9.6 years). INTERVENTION: Multi-professional, biopsychosocial-oriented pain program for the duration of 8 weeks. OUTCOMES: Pain intensity, Pain Disability Index (German Version of Pain Disability Index, PDI-G), cognitive and behavioral coping strategies (Verarbeitung chronischer Schmerzen FESV), Marburger questionnaire about habitual subjective well-being, and processing of chronic pain (Veränderungsfragebogen des Erlebens und Verhaltens, VEV). The migration background was considered to determine whether this variable influences the clinical outcomes. RESULTS: All the mentioned variables except pain intensity improved significantly after the program (P < 0.05); whereas, after the 1-year follow-up, most of the parameters returned to the baseline values. Solely the subscale "pain-related psychological strain" remained significantly better compared with baseline (P < 0.05). The variable "migration background" influenced the outcomes PDI-G, habitual well-being, and FESV (P < 0.001; variance of 16.7% [95% confidence interval 7.8-25.5]). After 12 months, 49.4% showed an improvement with regard to the VEV outcome measurement, 22.6% showed no changes, and 28% showed worsening of the symptoms. Gender and age did not influence the results at 12 months (P = 0.408; P = 0.964). CONCLUSION: This study provides evidence for the short-term effect of the IOPP in chronic pain patients as well as the long-term effect for the variable "pain-related psychological strain".

Do Chronic Pain Patients Wish Spiritual Aspects to Be Integrated in Their Medical Treatment? A Cross-Sectional Study of Multiple Facilities.

Background: Chronic pain is a complex, multidimensional experience. Spirituality is hypothesized to impact pain experience in various ways. Nevertheless, the role that spirituality plays in multimodal pain therapy remains controversial and, to date, quantitative data on whether and for which patients spiritual aspects should be considered in the treatment of chronic pain is lacking. The aim of this study was thus to investigate the proportion and characteristics of patients with chronic pain who wish spiritual aspects to be integrated in their treatment. Methods: Two hundred nine patients with chronic pain were recruited from five inpatient departments and outpatient clinics in the German-speaking part of Switzerland. Patients filled out validated questionnaires, such as the Hospital Anxiety and Depression Scale (HADS), the Resilience Scale (RS-11), the Spiritual and Religious Attitudes in Dealing with Illness (SpREUK), and the 12-item Spiritual Well-Being Scale (FACIT-Sp-12). Results: More than 60% (CI95%: 55.5-67.9%) of the patients wanted to address spiritual aspects in their treatment. These patients were significantly younger, had higher levels of education, and suffered from more frequent and more severe pain than patients who did not wish to address spiritual aspects. Furthermore, there were high correlations with existing spiritual resources and higher scores of spirituality. Conclusions: These results confirm that the majority of chronic pain patients wish spiritual aspects to be considered in their treatment. Additionally, the finding that these patients had more spiritual resources underlines the importance of integrating spiritual aspects in a resource-oriented, patient-centered care approach for this condition.

Including the Spiritual Dimension in Multimodal Pain Therapy. Development and Validation of the Spiritual Distress and Resources Questionnaire (SDRQ).

CONTEXT: Valid instruments for assessing spiritual resources and distress in pain therapy are scarce. The Spiritual Distress and Resources Questionnaire (SDRQ) was developed to fill this gap. GOALS: The objective of this study was to investigate the SDRQ's psychometric properties. METHODS: We presented the SDRQ to 219 patients with chronic pain conditions and examined its measurement properties, namely reliability and structural, convergent and discriminant validity. To investigate test-retest reliability, the SDRQ was presented a second time to a subsample of 58 randomly selected participants. RESULTS: Factor analysis required a grouping of the 22 SDRQ items into four subscales: spiritual distress, spiritual coping, immanence and transcendence, the latter two representing spiritual resources. Cronbach's alpha was high for spiritual distress (0.93), transcendence (0.85), and immanence (0.81) while it was somewhat lower but still satisfactory for spiritual coping (0.70). The construct validity of the SDRQ was shown by correlations with established measures in the field. Higher levels of spiritual distress were associated with signs of more severe illness, such as emotional distress and pain intensity. CONCLUSION: The results from this study suggest that the SDRQ is an easy-to-use, reliable and valid screening instrument for assessing spiritual distress, spiritual resources and spiritual coping in patients with chronic pain. The SDRQ has the potential to be used with patients suffering from other chronic diseases and to disseminate the palliative approach to pain treatment to other areas of medicine.

Goal attainment scaling as a measure of treatment success after physiotherapy for chronic low back pain.

OBJECTIVES: In some chronic conditions, patient-specific tools with individualized items have proved to be more sensitive outcome instruments than fixed-item tools; their use has not yet been investigated in chronic low back pain (cLBP). METHODS: Eleven males and 21 females [mean age 44.0 (12.3) years] with cLBP, undergoing a spine-stabilization physiotherapy programme, completed the Roland Morris (RM) Disability Scale and a 0-10 pain scale pre- and post-therapy. Post-therapy, goal attainment scaling (GAS) scores were calculated regarding achievement of 2-6 priority GAS goals established pre-therapy; global outcome of therapy was assessed on a 5-point Likert scale. RESULTS: Approximately one-fifth of the individualized goals were not covered by items of the RM. Of the 121 individualized goals, 41 (34%) were achieved at the expected level, 42 (35%) were exceeded and 38 (31%) were not reached. GAS scores correlated with change scores for pain (r = 0.61, P < 0.0001) and RM (r = 0.49, P = 0.006). Sixty-five per cent of the patients had a successful outcome according to GAS (i.e. a score >or=50); 55%, according to global outcome (therapy helped/helped a lot); 39%, according to the RM score change (score decrease >or=30%); and 44%, according to the pain score change (score decrease >or=30%). CONCLUSIONS: GAS demonstrates the achievement of important goals undetected by fixed-item measures and is a valid and sensitive outcome measure for assessing the success of rehabilitation in patients with cLBP.

Sleep quality, the neglected outcome variable in clinical studies focusing on locomotor system; a construct validation study.

BACKGROUND: In addition to general health and pain, sleep is highly relevant to judging the well-being of an individual. Of these three important outcome variables, however, sleep is neglected in most outcome studies.Sleep is a very important resource for recovery from daily stresses and strains, and any alteration of sleep will likely affect mental and physical health, especially during disease. Sleep assessment therefore should be standard in all population-based or clinical studies focusing on the locomotor system. Yet current sleep assessment tools are either too long or too specific for general use. METHODS: Based on a literature review and subsequent patient-based rating of items, an expert panel designed a four-item questionnaire about sleep. Construct validation of the questionnaire in a random sample of the German-speaking Swiss population was performed in 2003. Reliability, correlation, and tests for internal consistency and validity were analyzed. RESULTS: Overall, 16,634 (70%) out of 23,763 eligible individuals participated in the study. Test-retest reliability coefficients ranged from 0.72 to 0.87, and a Cronbach's alpha of 0.83 indicates good internal consistency. Results show a moderate to good correlation between sleep disturbances and health perception, and between sleep disturbances and overall pain. CONCLUSIONS: The Sleep Standard Evaluation Questionnaire (SEQ-Sleep) is a reliable and short tool with confirmed construct validity for sleep assessment in population-based observational studies. It is easy to administer and therefore suitable for postal surveys of the general population. Criterion validity remains to be determined.

Spinal segmental stabilisation exercises for chronic low back pain: programme adherence and its influence on clinical outcome.

Exercise rehabilitation is one of the few evidence-based treatments for chronic non-specific low back pain (cLBP), but individual success is notoriously variable and may depend on the patient's adherence to the prescribed exercise regime. This prospective study examined factors associated with adherence and the relationship between adherence and outcome after a programme of physiotherapeutic spine stabilisation exercises. A total of 32/37 patients with cLBP completed the study (mean age, 44.0 (SD = 12.3) years; 11/32 (34%) male). Adherence to the 9-week programme was documented as: percent attendance at therapy, percent adherence to daily home exercises (patient diary) and percent commitment to rehabilitation (Sports Injury Rehabilitation Adherence Scale (SIRAS)). The average of these three measures formed a multidimensional adherence index (MAI). Psychological disturbance, fear-avoidance beliefs, catastrophising, exercise self-efficacy and health locus of control were measured by questionnaire; disability in everyday activities was scored with the Roland-Morris disability scale and back pain intensity with a 0-10 graphic rating scale. Overall, adherence to therapy was very good (average MAI score, 85%; median (IQR), 89 (15)%). The only psychological/beliefs variable showing a unique significant association with MAI was exercise self-efficacy (Rho = 0.36, P = 0.045). Pain intensity and self-rated disability decreased significantly after therapy (each P < 0.01). Adherence to home exercises showed a moderate, positive correlation with the reduction in average pain (Rho = 0.54, P = 0.003) and disability (Rho = 0.38, P = 0.036); higher MAI scores were associated with greater reductions in average pain (Rho = 0.48, P = 0.008) and a (n.s.) tendency for greater reductions in disability (Rho = 0.32, P = 0.07) Neither attendance at therapy nor SIRAS were significantly related to any of the outcomes. The benefits of rehabilitation depended to a large extent on the patient's exercise behaviour outside of the formal physiotherapy sessions. Hence, more effort should be invested in finding ways to improve patients' motivation to take responsibility for the success of their own therapy, perhaps by increasing exercise self-efficacy. Whether the "adherence-outcome" interaction was mediated by improvements in function related to the specific exercises, or by a more "global" effect of the programme, remains to be examined.

Cross-cultural adaptation, reliability, and validity of the German version of the Pain Catastrophizing Scale.

OBJECTIVE: In patients with chronic pain, catastrophizing is a significant determinant of self-rated pain intensity and disability. The Pain Catastrophizing Scale (PCS) was developed to assist with both treatment planning and outcome assessment; to date, no German version has been validated. METHODS: A cross-cultural adaptation of the PCS into German was carried out, strictly according to recommended methods. A questionnaire booklet containing the PCS, visual analogue scales (numeric rating scale) for pain intensity and general health, the ZUNG self-rating depression scale, the Modified Somatic Perception Questionnaire (MSPQ), the Fear Avoidance Beliefs Questionnaire (FABQ), and the Roland-Morris (RM) disability questionnaire was completed by 111 patients with chronic low back pain (mean age, 49 years), 100 of which also completed it again 7 days later. RESULTS: Cronbach's alpha (internal reliability) for the three subsections of the PCS--helplessness, magnification, rumination--and for the whole questionnaire (PCSwhole) were .89, .67, .88, and .92, respectively. The intraclass correlation coefficients of agreement for the reproducibility were .81, .67, .78, and .80, respectively. The PCSwhole scores correlated with the other scores as follows: pain intensity r=.26, general health r=-.29, ZUNG r=.52, MSPQ r=.53, FABQactivity r=.51, FABQwork r=.61 and RM r=.57. Factor analysis revealed three factors, with an almost identical factor structure to that reported in previous studies. CONCLUSION: The psychometric properties of our German version of the PCS were comparable to those reported in previous studies for the original English version. It represents a valuable tool in the assessment of German-speaking chronic low back pain patients.

Use of the Short-Form-36 Health Survey to detect a subgroup of fibromyalgia patients with psychological dysfunction.

The aim of the present study was to examine the in-depth application of the Short-Form-(SF)-36 Health Survey to score the general well-being in fibromyalgia syndrome (FS) patients. Quality of life was evaluated in 12 patients with FS. With respect to mental well-being (social functioning, role limitation due to emotional health problems, and mental health), two distinguished groups were found concerning psychological functioning. One group (n = 8) demonstrated psychological dysfunction, whereas the other (n = 4) showed normal psychological scores. Physical well-being scores (physical functioning, role limitation due to physical health problems, bodily pain, general health, and vitality) did not differ between FS patients but were altogether below the normal range. Regarding the psychological scores of the two groups of patients, SF-36 can be used to differentiate between patients with and without psychological dysfunction independent of pain. Therefore, we propose that the SF-36 could be of help to provide the most adequate therapy to achieve an optimal outcome in patients with FS and psychological disturbances.

Muscle thickness changes during abdominal hollowing: an assessment of between-day measurement error in controls and patients with chronic low back pain.

Spine stabilization exercises, in which patients are taught to perform isolated contractions of the transverses abdominus (TrA) during "abdominal hollowing", are a popular physiotherapeutic treatment for low back pain (LBP). Successful performance is typically judged by the relative increase in TrA thickness compared with that of the internal (OI) and external (OE) oblique muscles, measured using ultrasound. The day-to-day measurement error (imprecision) associated with these indices of preferential activation has not been assessed but is important to know since it influences the interpretation of changes after treatment. On 2 separate days, 14 controls and 14 patients with chronic LBP (cLBP) performed abdominal hollowing exercises in hook-lying, while M-mode ultrasound images superimposed with tissue Doppler imaging (TDI) data were recorded from the abdominal muscles (N = 5 on each side). The fascial lines bordering the TrA, OI and OE were digitized, and muscle thicknesses were calculated. The between-day error (intra-observer) was expressed as the standard error of measurement, SEM; SEM as a percentage of the mean gave the coefficient of variation (CV). There were no significant between-day differences for the mean values of resting or maximal thickness for any muscle, in either group (P > 0.05). The median SEM and CV of all thickness variables was 0.71 mm and 10.9%, respectively for the controls and 0.80 mm or 11.3%, respectively for the cLBP patients. For the contraction ratios (muscle thickness contracted/thickness at rest), the CVs were 3-11% (controls) and 5-12% (patients). The CVs were unacceptably high (30-50%, both groups) for the TrA preferential activation ratio (TrA proportion of the total lateral abdominal muscle thickness when contracted minus at rest). In both the controls and patients, the precision of measurement of absolute muscle thickness and relative change in thickness during abdominal hollowing was acceptable, and commensurate with that typical of biological measurements. The TrA preferential activation ratio is too imprecise to be of clinical use. Knowledge of the SEM for these indices is essential for interpreting the clinical relevance of any changes observed following physiotherapy.

Chronic nonmalignant pain: a challenge for patients and clinicians.

Chronic pain is widely regarded as a condition that is triggered by various factors, including physical, socio-cultural and psychological deficiencies (that is, maladaptive beliefs). These factors are important in the development and maintenance of this unpleasant experience, which consequently requires a biopsychosocial treatment approach. Pain is a multifaceted sense, the perception of which is personal. Pain also depends on various circumstances, and therefore represents a challenge for the patient, as well for the treating physicians. Patients who suffer from long-lasting pain with a predominantly psychosocial component should be referred to specialized pain clinics for further diagnostic assessment and possible allocation to multidisciplinary pain programs. High-quality randomized controlled trials indicate that multidisciplinary pain programs represent the best therapeutic option for the management of patients with complaints associated with complex chronic pain. The prevalence and the costs--both direct and indirect--that are attributed to chronic pain are increasing; however, not enough is being done to sufficiently and effectively treat chronic pain. There is, therefore, a need for well-designed, interdisciplinary, internationally comparable, and widely distributed pain programs, both in outpatient and inpatient settings, to contribute to the prevention of some future pain diseases.

Pain-Associated Transcriptome Changes in Synovium of Knee Osteoarthritis Patients.

Joint pain causes significant morbidity in osteoarthritis (OA). The aetiology of joint pain in OA is not well understood. The synovial membrane as an innervated joint structure represents a potential source of peripheral pain in OA. Here we analyse, using a hypothesis-free next generation RNA sequencing, the differences in protein-coding and non-coding transcriptomes in knee synovial tissues from OA patients with high knee pain (n = 5) compared with OA patients with low knee pain (n = 5), as evaluated by visual analogue scale (VAS). We conduct Gene Ontology and pathway analyses on differentially expressed mRNA genes. We identify new protein-coding, long non-coding RNA and microRNA candidates that can be associated with OA joint pain. Top enriched genes in painful OA knees encode neuronal proteins that are known to promote neuronal survival under cellular stress or participate in calcium-dependent synaptic exocytosis and modulation of GABA(γ-aminobutyric acid)ergic activity. Our study uncovers transcriptome changes associated with pain in synovial microenvironment of OA knees. This sets a firm ground for future mechanistic studies and drug discovery to alleviate joint pain in OA.

Nondermatomal somatosensory deficits in chronic pain are associated with cerebral grey matter changes.

OBJECTIVES: Widespread sensory deficits occur in 20-40% of chronic pain patients on the side of pain, independent of pain aetiology, and are known as nondermatomal sensory deficits (NDSDs). NDSDs can occur in absence of central or peripheral nervous system lesions. We hypothesised that NDSDs were associated with cerebral grey matter changes in the sensory system and in pain processing regions, detectable with voxel-based morphometry. METHODS: Twenty-five patients with NDSDs, 23 patients without NDSDs ("pain-only"), and 29 healthy controls were studied with high resolution structural MRI of the brain. A comprehensive clinical and psychiatric evaluation based on Diagnostic and Statistical Manual was performed in all patients. RESULTS: Patients with NDSDs and "pain-only" did not differ concerning demographic data and psychiatric diagnoses, although anxiety scores (HADS-A) were higher in patients with NDSDs. In patients with NDSDs, grey matter increases were found in the right primary sensory cortex, thalamus, and bilaterally in lateral temporal regions and the hippocampus/fusiform gyrus. "Pain-only" patients showed a bilateral grey matter increase in the posterior insula and less pronounced changes in sensorimotor cortex. CONCLUSIONS: Dysfunctional sensory processing in patients with NDSDs is associated with complex changes in grey matter volume, involving the somatosensory system and temporal regions.

Bilateral Sensory Changes and High Burden of Disease in Patients With Chronic Pain and Unilateral Nondermatomal Somatosensory Deficits: A Quantitative Sensory Testing and Clinical Study.

OBJECTIVES: Widespread sensory deficits resembling hemihypoesthesia occur in 20% to 40% of chronic pain patients on the side of pain, independent of pain etiology, and have been termed nondermatomal sensory deficits (NDSDs). Sensory profiles have rarely been investigated in NDSDs. MATERIALS AND METHODS: Quantitative sensory testing according to the protocol of the German Research Network on Neuropathic Pain (DFNS) was performed in the face, hand, and foot of the painful body side and in contralateral regions in chronic pain patients. Twenty-five patients with NDSDs and 23 without NDSDs (termed the pain-only group) were included after exclusion of neuropathic pain. Comprehensive clinical and psychiatric evaluations were carried out. RESULTS: NDSD in chronic pain was associated with high burden of disease and more widespread pain. Only in the NDSD group were significantly higher thresholds for mechanical and painful stimuli found in at least 2 of 3 regions ipsilateral to pain. In addition, we found a bilateral loss of function for temperature and vibration detection, and a gain of function for pressure pain in certain regions in patients with NDSD. Sensory loss and gain of function for pressure pain correlated with pain intensity in several regions. DISCUSSION: This may indicate a distinct sensory profile in chronic non-neuropathic pain and NDSD, probably attributable to altered central pain processing and sensitization. The presence of NDSD in chronic non-neuropathic pain may be regarded as a marker for higher burden of pain disease.

Prospective epidemiological observations on the course of the disease in fibromyalgia patients.

OBJECTIVES: The aim of the study was to carry out a survey in patients with fibromyalgia (FM), to examine their general health status and work incapacity (disability-pension status), and their views on the effectiveness of therapy received, over a two-year observation period. METHODS: 48 patients diagnosed with FM, according to the American College of Rheumatology (ACR) criteria, took part in the study. At baseline, and on average two years later, the patients underwent clinical investigation (dolorimetry, laboratory diagnostics, medical history taking) and completed the Fibromyalgia questionnaire (Dettmer and Chrostek 1). RESULTS: 27/48 (56%) patients participated in the two-year follow-up. In general, the patients showed no improvement in their symptoms over the observation period, regardless of the type of therapy they had received. General satisfaction with quality of life improved, as did satisfaction regarding health status and the family situation, although the degree of pain experienced remain unchanged. In comparison with the initial examination, there was no change in either work-capacity or disability-pension status. CONCLUSIONS: The FM patients showed no improvement in pain, despite the many various treatments received over the two-year period. The increase in general satisfaction over the observation period was believed to be the result of patient instruction and education about the disease. To what extent a population of patients with FM would show similar outcomes if they did not receive any instruction/education about their disorder, cannot be ascertained from the present study; and, indeed, the undertaking of a study to investigate this would be ethically questionable. As present, no conclusions can be made regarding the influence of therapy on the primary and secondary costs associated with FM.