Blog Title: Fibromyalgia Research Blog

Neurocognitive Defects & Brain Structure in Fibromyalgia: Are Pain & Cognitive Problems Related?

The journal Brain [2008 Sep 26] just published a study on a fascinating study from the University of Regensburg's Clinic for Rheumatology in Germany. The researchers write that fibromyalgia patients often report memory and attention problems in addition to pain, stiffness and sleep disturbance. While "[a]ccumulating evidence suggests that [fibromyalgia] is associated with CNS [central nervous system] dysfunction and with an altered brain morphology," there have been few studies that have specifically focused on fibromyalgia patients' neuropsychological issues. Therefore the authors of this study aimed to determine whether fibromyalgia patients' memory and attention problems have any correllation with changes in the morphology (structure and shape) of the brain. They focused specifically on the frontal, temporal and cingulate cortices.

Twenty [fibromyalgia] patients underwent extensive testing for potential neuropsychological deficits, which demonstrated significantly reduced working memory and impaired non-verbal long-term memory (limited to free recall condition) in comparison with normative data from age- and education-matched control groups.

On the other hand, pain scores were negatively correlated with grey matter values in the medial frontal gyrus. White matter analyses revealed comparable correlations for verbal working memory and pain scores in the medial frontal and prefrontal cortex and in the anterior cingulate cortex.

Our data suggest that, in addition to chronic pain, [fibromyalgia] patients suffer from neurocognitive deficits that correlate with local brain morphology in the frontal lobe and anterior cingulate gyrus, which may be interpreted to indicate structural correlates of pain-cognition interaction.

Study Reveals Subgroups of Fibromyalgia Patients - Not All Experience Psychological Distress

In an article entitled Fibromyalgia subgroups: profiling distinct subgroups using the Fibromyalgia Impact Questionnaire, researchers at the Université de Sherbrooke in Quebec, Canada, describe the results of their investigation of whether there are multiple types of fibromyalgia. Published in Rheumatology International [2008 Sep 27], the article describes the goal of the research study as identifying fibromyalgia subgroups using a "simple and frequently used clinical tool, the Fibromyalgia Impact Questionnaire (FIQ)."

A total of 61 women diagnosed with [fibromyalgia] participated in this study. [Fibromyalgia] subgroups were created by applying a hierarchical cluster analysis on selected items of the FIQ (pain, fatigue, morning tiredness, stiffness, anxiety and depressive symptoms). We also tested for group differences on experimental pain, psychosocial functioning and demographic characteristics.

FDA Approves Cymbalta for Fibromyalgia

The FDA approved duloxetine (Cymbalta) as a medication for fibromyalgia earlier this week. Cymbalta is a serotonin-norepinphrine reuptake inhibitor. It is also used for anxiety, major depression and peripheral diabetic neuropathy. It has been shown to be effective for some fibromyalgia patients. Cymbalta, made by Lilly, is the second drug to ever be approved for fibromyalgia. Last year Lyrica (pregabalin), an anti-convulsant, became the first fibromyalgia drug approved by the FDA.

The added indication [for fibromyalgia] was approval on the basis of data from two three-month clinical trials of 874 fibromyalgia patients. In both studies, compared with placebo, duloxetine was associated with more than a 30% reduction in pain as measured by the Brief Pain Inventory (BPI) 24-hour average pain scale.

Moreover, patients randomized to duloxetine reported significant pain relief during the first week of treatment.

In both studies the majority of duloxetine patients -- 65% in one study and 66% in the other -- said they felt better since beginning treatment with 60 mg of duloxetine daily, as measured by a self-assessment (Patient Global Impression of Improvement).

Are Fibromyalgia Patients More Sensitive to Sound?

Fibromyalgia is characterized by widespread tenderness, including sensitivity to touch. But do fibromyalgia patients also more sensitive to other stimuli, such as sound? In their article A Psychophysical Study of Auditory and Pressure Sensitivity in
Patients With Fibromyalgia and Healthy Controls, researchers at the Chronic Pain and Fatigue Research Center at the University of Michigan, Ann Arbor, discuss their recent research into this question [Journal of Pain, 2008 Feb 14]. Because past studies reported that people with fibromyalgia are sensitive to other stimuli, such as auditory tones, they hypothesized "that subjects with [fibromyalgia] would display greater sensitivity to both pressure and auditory tones and report greater sensitivity to sounds encountered in daily activities" and that fibromyalgia involves a global central nervous system amplification of sensory information.

The study administered auditory tones and physical pressure to 30 fibromyalgia patients and 28 healthy controls. They used the same psychophysical methods to deliver the stimuli and a similar way of scaling responses. Subjects also completed a self-report questionnaire regarding sensitivity to everyday sounds.

Participants with [fibromyalgia] displayed significantly greater sensitivity to all levels of auditory stimulation (Ps < .05). The magnitude of difference between [fibromyalgia] patients' lowered auditory sensitivity (relative to control subjects) was similar to that seen with pressure, and pressure and auditory ratings were significantly correlated in both control subjects and subjects with [fibromyalgia]... patients also were more sensitive to everyday sounds (t = 8.65, P < .001).

Cost-Effectiveness of Aquatic Training for Women with Fibromyalgia

The results of a randomized controlled trial were published in the most recent issue of Arthritis Research and Therapy [2008 Feb 22;10(1):R24]. Knowing that physical therapy in warm water has been shown to be highly effective for fibromyalgia patients, the study was designed to evaluate whether it is an efficient investment for patients or health care managers. The research aimed to "assess the cost-utility of adding an aquatic exercise programme to the usual care of women with fibromyalgia."

The study evaluated costs to the health care system and to society. It included 33 participants, all women with fibromyalgia. Seventeen participants were randomly assigned to an experimental group and sixteen to a control group.

The intervention in the experimental group consisted of a one-hour, supervised, water-based exercise sessions, three times per week for 8 months. The main outcome measures were the health care costs and the number of quality-adjusted life-years (QALYs) using the time trade-off elicitation technique from the EQ-5D. Sensitivity analyses was performed for variations in the staff salary, number of women attending sessions and time spent going to the pool. The cost-effectiveness acceptability curves were created using a non-parametric bootstrap technique.

Study Suggests Fibromyalgia Pain is Neuropathic

In the March issue of the journal Pain Medicine [2008 Mar;9(2):149-160] researchers at three institutions in Florida conducted a study to determine whether the neuropathic pain scale (NPS) can be used to classify chronic pain patients (CPPs) as having primarily neuropathic vs non-neuropathic pain, as well as to determine whether there is a cut-off score that can be used reliably to make this distinction between types of pain. This study evaluated 305 chronic pain patients (CPPs) admitted to The Rosomoff Pain Center (Miami, FL). All were administered the NPS, a diagnostic tool designed to assess the distinct pain qualities associated with neuropathic pain, and were given a diagnosis on the basis of a physical examination and all available test results.

Using patients known to have neuropathic or non-neuropathic pain conditions as a reference, esearchers were able to derive "an NPS cut-off score above which CPPs would be classified as having neuropathic pain." Patients who had diagnoses of myofascial pain syndromes, spinal stenosis, epidural fibrosis, fibromyalgia, complex regional pain syndromes, and failed back surgery syndrome, a predicted NPS score was calculated and compared with the cut-off score.

The NPS appeared to be able to separate CPPs into neuropathic pain vs non-neuropathic pain subtypes. The cut-off score the researchers derived was 5.53 on the NPS. Myofascial pain syndrome and spinal stenosis had scores lower than this cut-off score at 3.81 and 4.26, respectively - Therefore they did not meet the criteria for neuropathic pain. Epidural fibrosis, fibromyalgia, complex regional pain syndromes, and failed back surgery syndrome had predictive scores higher than the cut-off score at 6.15, 6.35, 6.87, 9.34, and 7.19, respectively. Thus, these syndromes did meet the qualifications for neuropathic pain according to this study's criteria. The researchers conclude that the NPS does appear to be able to discriminate between patients experiencing neuropathic and non-neuropathic pain.

A debate is currently raging as to whether diagnoses, such as fibromyalgia and complex regional pain syndrome 1, can be classified as neuropathic. Our NPS cut-off score results suggest that these diagnoses may have a neuropathic pain component. The reliability and validity of our NPS method will need to be tested further in other neuropathic pain models, such as diabetic peripheral neuropathic pain.

Immunological Changes in Fibromyalgia & Other Chronic Pain Conditions?

The newest issue of the medical journal Neuroimmunomodulation [2008 Feb 1;14(5):272-280] includes the results of a study conducted by Department of Anesthesiology of Ludwig Maximilians University, Munich, Germany. The study address immunological changes in chronic pain patients, specifically complex regional pain syndrome (CRPS) and fibromyalgia (FMS), both of which the researchers describe as "chronic pain syndromes occurring in highly stressed individuals."

Despite the known connection between the nervous system and immune cells, information on distribution of lymphocyte subsets under stress and pain conditions is limited. Lymphocytes are white blood cells that play a critical role in the body's defenses. They include T cells, B cells, and natural killer cells. They also modulate the activities of other cells.

The researchers performed a comparative study of 15 patients with CRPS, 22 patients with FMS and 37 age- and sex-matched healthy controls. Their aim was to investigate the influence of pain and stress on lymphocyte number, subpopulations and the Th1/Th2 cytokine ratio in T lymphocytes.

Lymphocyte numbers did not differ between the groups studied. However, when the subtypes of lymphocytes were studied using quantitative analyses, it became evident that there was "a significant reduction of cytotoxic CD8+ lymphocytes in both CRPS... and [fibromyalgia]... patients as compared with healthy controls. Additionally, CRPS patients were characterized by a lower percentage of IL-2-producing T cell subpopulations reflecting a diminished Th1 response in contrast to no changes in the Th2 cytokine profile."

The article concludes that future studies are necessary in order to answer "whether such immunological changes play a pathogenetic role in CRPS and [FMS] or merely reflect the consequences of a pain-induced neurohumoral stress response, and whether they contribute to immunosuppression in stressed chronic pain patients."

Effects of the Drug Pyridostigmine Along with Exercise in Treatment of Fibromyalgia

A subset of fibromyalgia patients are known to have a dysfunctional hypothalamic-pituitary-insulin-like growth factor 1 (IGF-1) axis, which is diagnosed by low blood serum levels of IGF-1 and a reduced growth hormone (GH) response to physiologic stimuli. There is evidence that the drug pyridostigmine (PYD) can improve the acute response of growth hormone to exercise in fibromyalgia patients. Researchers at Oregon Health & Science University in Portland, OR, conducted a 6-month randomized controlled trial of pyridostigmine in conjunction with exercise, in order to evaluate the effectiveness of this treatment on fibromyalgia treatment.

The purpose of this study was to evaluate the clinical effectiveness of 6 months of PYD and group exercise on [fibromyalgia] symptoms. The researchers randomized patients into one of four groups: PYD PYD plus exercise, PYD without exercise but with diet recall, placebo plus exercise, and placebo plus diet recall but no exercise. To assess the results of the treatments, they used the visual analog scale (VAS) score for pain, tender point count, and total myalgic score. They also used other secondary outcome measures including the Fibromyalgia Impact Questionnaire (FIQ) and scores for individual symptoms (fatigue, poor sleep, stiffness, and anxiety), as well as quality of life (QOL) evluation and level of physical fitness (lower body strength/endurance, upper and lower body flexibility, balance, and time on the treadmill).

A total of 165 [fibromyalgia] patients completed baseline measurements; 154 (93.3%) completed the study. The combination of PYD and exercise did not improve pain scores. PYD groups showed a significant improvement in sleep and anxiety in those who completed the study and in QOL in those who complied with the therapeutic regimen as compared with the placebo groups. Compared with the nonexercise groups, the 2 exercise groups demonstrated improvement in fatigue and fitness. PYD was generally well tolerated.

The research team concluded that "neither the combination of PYD plus supervised exercise nor either treatment alone yielded improvement in most fibromyalgia symptoms." However, they noted that pyridostigmine (PYD) did improve anxiety and sleep, and exercise improved fatigue and fitness. They speculate that pyridostigmine (PYD) "may have improved vagal tone, thus benefiting sleep and anxiety; this notion warrants further study."

Online Support Groups Empowering for Patients with Fibromyalgia & Other Conditions

In an article in the journal Qualitative Health Research [2008 Mar;18(3):405-17] researchers at the University of Twente in the Netherlands present the results of their research into the effects of online support groups on the wellbeing of fibromyalgia, breast cancer and arthritis patients.

Ever since the rise of online support groups it has been presumed that there is an empowering effect from patients' participating in these groups, despite a lack of evidence to back up this assumption. In this study we explored if, and in which ways, patients feel empowered by participation. Additionally, we studied which empowering and disempowering processes occur as a result of taking part in these groups.

Empowering outcomes mentioned were being better informed; feeling confident in the relationship with their physician, their treatment, and their social environment; improved acceptance of the disease; increased optimism and control; enhanced self-esteem and social well-being; and collective action.

Medications for Fibromyalgia

According to an article in the Italian rheumatology journal Reumatismo [2007;59(4):280-291], the medications Italian physicians have found the most effective for fibromyalgia "include the tricyclic drugs and mixed reuptake inhibitors. Recent works suggest that the anticonvulsant medications pregabalin and gabapentin are also effective. Moreover, two serotonin and norepinephrine-reuptake inhibitors-duloxetine and milnacipran show encouraging results in treating FM symptoms. The results of clinical trials of anti-inflammatory medications have been generally disappointing, but three RCTs have found that tramadol (with or without acetaminophen) is effective in FM.

Effects of Yoga and Tui Na on Fibromyalgia

A study conducted by the Pulmonary Division at University of São Paulo (Brazil) intended to verify whether techniques of yoga with and without the addition of traditional Chinese medicine modality Tui Na would "improve pain and the negative impact of fibromyalgia on patients' daily life." The results are published in the Journal of Alternative and Complementary Medicine [2007 Dec; 13(10):1107-14].

Forty women with fibromyalgia were randomly assigned to two groups. One group participated in Relaxing Yoga (RY) and the other received Relaxing Yoga plus Touch (RYT), for "eight weekly sessions of stretching, breathing, and relaxing yogic techniques." RYT patients also received manipulative techniques of Tui Na, an ancient hands-on Chinese technique that uses acupressure to bring the body into balance.

The outcome of the study was measured using the Fibromyalgia Impact Questionnaire (FIQ), pain threshold at the 18 FMS tender points, and a verbal assessment of pain. The visual analog scale (VAS) for pain was assessed before and after each session and on the follow-up.

Seventeen (17) RYT and 16 RY patients completed the study. Both RY and RYT groups showed improvement in the FIQ and VAS scores, which decreased on all sessions. The RYT group showed lower VAS and verbal scores for pain on the eighth session, but this difference was not maintained on the follow-up. Conversely, RY VAS and verbal scores were significantly lower just on the follow-up.

Warm Water Exerise Effective for Fibromyalgia Symptom Relief

In the most recent issue of Clinical and Experimental Rheumatology [2007 Nov-Dec;25(6):823-30] researchers at the Section of Physical Education and Sports, University Pablo de Olavide, Seville (Spain) describe their study of the effects of warm water exercise on middle-aged women with fibromyalgia. They aimed to compare cognitive function between fibromyalgia patients and health controls, as well as to evaluate the efficacy of warm water exercise.

Sixty middle-aged women with fibromyalgia were randomly assigned to either an exercise training group that participated in 3 sessions a week of aquatic training in chest-high 32 C / 89.6 F water for 16 weeks. The program included mobility, aerobic, strengthening, and relaxation exercises. The control group did not receive this treatment. Twenty-five healthy women without fibromyalgia were also assessed. Pain was assessed in patients using pressure applied by a "syringe calibrated like a pressure dolorimeter", and a visual analog scale.

The severity of [fibromyalgia] was evaluated using the Fibromyalgia Impact Questionnaire. Cognitive function was measured in healthy individuals and patients using several standardized neuropsychological tests. All patients were measured at baseline and post-treatment.

An exercise therapy three times per week for 16 weeks in a warm-water pool is an adequate treatment to decrease the pain and severity of [fibromyalgia] as well as to improve cognitive function in previously unfit women with [fibromyalgia] and heightened painful symptomatology.

Nabilone (Synthetic Cannibanoid) for the Treatment of Fibromyalgia Pain

Research conducted at the University of Manitoba's Rehabilitation Hospital [Canada] into the effectiveness of a synthetic cannibanoid for fibromyalgia pain was recently published in the Journal of Pain [2007 Oct 30] .

Nabilone is a synthetic cannabinoid that mimics THC, the main ingredient of marijuana, but it can be dosed more uniformly and has more predictable side effects. It causes no or minimal euphoria, and is not derived from the cannabis plant. Nabilone has been used medically as an anti-nausea drug as well as for neuropathic pain. It is sold in many countries as a drug called Cesamet and is FDA approved in the US for the treatment of chemotherapy-induced nausea and vomiting as well as for the treatment of anorexia and weight loss in AIDS patients. It is widely used "off-label" as an adjunct therapy for chronic pain management. Studies have shown it has benefits for multiple sclerosis as well as fibromyalgia.

Fibromyalgia Has Highly Negative Impact on Lives of Muslim Bedouin Women

Though research frequently focuses on patient populations in urban areas of developed countries, fibromyalgia "has been described and studied in various sociocultural settings in both developed and developing countries." In their study published in Seminars in Arthritis and Rheumatism [2007 Oct 29] researchers at Ben Gurion University of the Negev (Beer Sheva, Israel) aimed to assess the clinical manifestations of fibromyalgia and describe its effect on quality of life in the "unique setting of Muslim Bedouin women in the southern Israel Negev desert area."

They evaluated 102 Bedouin women were recruited from a primary health care clinic in the Negev, all of whom fulfilled the American College of Rheumatology (ACR) criteria for fibromyalgia diagnosis. Tender points were assessed using manual dolorimetry (an instrument used to measure pain tolerance) and pain level, anxiety, depression, and quality of life were also assessed using various questionnaires.

Transcranial Direct Current Stimulation for Pain and Sleep

Medical researchers from the Department of Psychobiology, Universidade Federal de São Paulo (São Paulo, Brazil) conducted a randomized, sham-controlled study on the "site-specific effects of transcranial direct current stimulation on sleep and pain in fibromyalgia." The results are published in Pain Practice (2007 Nov 6).

Transcranial direct current stimulation (tDCS) involves applying weak electrical currents to the body so that the electromagnetic field they create will modulate the activity of brain neurons. It has been found to alter neuron firing rates. It is being studied as a treatment for a variety of conditions such as stroke recovery, depression and migraines. Do not confuse tDCS with electroconvulsive therapy or transcranial magnetic stimulation. tDCS does not independently cause nerve cells to fire, nor does it cause muscle twitches, seizures or other negative side effects of older forms of electrical stimulation.

The fibromyalgia sleep and pain study investigated whether or not transcranial direct current stimulation (tDCS) of two different parts of the brain, dorsolateral prefrontal cortex [DLPFC] and primary motor cortex [M1], would be more effective than sham treatment in its impact on the sleep patterns of fibromyalgia sufferers.

Thirty-two patients randomly received sham stimulation or active tDCS with the anode centered over M1 or DLPFC (2 mA, 20 minutes for five consecutive days). "A blinded evaluator rated the clinical symptoms of fibromyalgia. All-night polysomnography was performed before and after five consecutive sessions of tDCS."

The results of the study showed that anodal tDCS did have an effect on both sleep and pain that was specific to what site was stimulated. Stimulation of M1 and DLPFC treatments induced opposite effects on sleep and pain, whereas sham stimulation induced no significant sleep or pain changes.

Specifically, M1 treatment significantly increased increased sleep efficiency and decreased arousals, whereas DLPFC stimulation was decreased sleep efficiency, increased rapid eye movement (REM) latency (the time it takes to go from wakefulness to REM sleep) and sleep latency (the time it takes to go from full wakefulness to the point where you have fallen asleep). "A decrease in REM latency and increase in sleep efficiency were associated with an improvement in fibromyalgia symptoms (as indexed by the Fibromyalgia Impact Questionnaire)." The study also found that patients with a higher body mass index (BMI) had the worse sleep outcome as evaluated by changes in sleep efficiency after M1 stimulation.

The researchers conclude that "[o]ur findings suggest that one possible mechanism to explain the therapeutic effects of tDCS in fibromyalgia is via sleep modulation that is specific to modulation of primary M1 activity."

Muscle Strengthening vs. Aerobic Exercise for Fibromyalgia

What is more effective in the treatment of fibromyalgia, aerobic exercise or muscle strengthening? That is what researchers at the Department of Physical Medicine and Rehabilitation, Dokuz Eylül University (Ýzmir, Turkey) decided to find out. This month's edition of Rheumatology International [2007 Nov 3] reveals their conclusions.

The study involved 30 women with fibromyalgia who were randomly assigned to either an aerobic exercise (AE) program or a strengthening exercise (SE) program for eight weeks. "Outcome measures included the intensity of fibromyalgia-related symptoms, tender point count, fitness (6-min walk distance), hospital anxiety and depression (HAD) scale, and short-form health survey (SF-36)."

There were significant improvements in both groups regarding pain, sleep, fatigue, tender point count, and fitness after treatment. HAD-depression scores improved significantly in both groups while no significant change occurred in HAD-anxiety scores. Bodily pain subscale of SF-36 and physical component summary improved significantly in the AE group, whereas seven subscales of SF-36, physical component summary, and mental component summary improved significantly in the SE group. When the groups were compared after treatment, there were no significant differences in pain, sleep, fatigue, tender point count, fitness, HAD scores, and SF-36 scores.

The study shows that both types of exercise are more or less equally effective in improving symptoms for fibromyalgia. In particular they both have similar effects on reducing tender point count, improving fitness, reducing depression, and increasing quality of life. However, neither were shown to affect the anxiety that plagues some fibromyalgia patients.

Does Resistance Exercise Improve Heart Rate Variability in Women with Fibromyalgia?

In the journal Clinical Physiology and Functional Imaging this month, researchers in the Department of Nutrition, Food and Exercise Sciences at Florida State University (Tallahassee, FL) present their findings regarding treating the reduced heart rate variability (HRV) that is found in fibromyalgia patients. Reduced heart rate variability increases fibromyalgia patients' risk for illness and death from cardiovascular problems.

The researchers hypothesized that resistance exercise training (RET) would improve heart rate variability, baroreflex (a bodily mechanism for maintaining blood pressure) sensitivity and muscle strength in women with fibromyalgia. They studied 10 FMS patients and 9 healthy controls, aged 27-60 years. Only women with fibromyalgia underwent RET two days per week for 16 weeks. Both groups of subjects were measured before and after the intervention and evaluated on their HRV and spontaneous baroreflex sensitivity (BRS) using a continuous electrocardiogram as well as blood pressure monitoring using finger plethysmography.

At baseline "RR interval, total power, log transformed (Ln) squared root of the standard deviation of RR interval (RMSSD), low-frequency power and BRS were lower... and [heart rate] and pulse pressure were higher in women with fibromyalgia than in healthy controls." After the resistance exercise treatment, "mean total power increased, RMSSD increased and Ln of high-frequency power increased in women with FM. Upper and lower body muscle strength increased by 63% and 49%... and pain perception decreased by 39% in women with FM." No changes were found in baroreflex sensitivity, heart rate and blood pressure after the treatment.

The researchers conclude as follows:

Our study demonstrates that RET improves total power, cardiac parasympathetic tone, pain perception and muscle strength in women with fibromyalgia who had autonomic dysfunction before the exercise programme.

1 in 4 Chronic Pain Patients Has Vitamin D Deficiency, Which Can Worsen Pain

Vitamin D deficiency has been known for a while to be common in fibromyalgia patients, and research has even linked it with anxiety and depression in fibromyalgia. New research, however, shows that Vitamin D deficiency may in fact cause worsening of chronic pain in general. The American Society of Anesthesiologists recently released results of a Mayo Clinic study that shows that 1/4 of chronic pain patients have inadequate blood levels of vitamin D. The study also suggests that such a deficiency can possibly contribute to the severity of chronic pain. Their study showed that patients who have vitamin D deficiency needed a higher dose of morphine for a longer time in order to alleviate their pain.

Researchers recorded the serum vitamin D levels of 267 adults undergoing outpatient treatment for chronic pain, as well as their pain medication (morphine) dose and duration of use, and physical and general health functioning. Of the patients tested, 26 percent had vitamin D inadequacy. Among these patients, the morphine dose was nearly twice that of the group with adequate vitamin D levels. In addition, the vitamin D inadequacy group used morphine for an average of 71.1 months versus 43.8 months. The vitamin D deficient group also reported lower levels of physical functioning and had a poorer view of their overall health.

Abnormalities Found in Nerve Cells in the Skin of Fibromyalgia Patients

In this month's Clinical Rheumatology [2007 Oct 3], researchers at Dongguk University College of Medicine in South Korea published the results of a blinded study conducted to "determine if there are any abnormal electron microscopic (EM) findings in the skin of fibromyalgia syndrome (FMS) patients, which might contribute to or be due to the increased pain sensitivity seen in this condition."

They collected skin biopsy samples from 13 fibromyalgia patients and 5 control subjects, which were read by an individual who did not have any knowledge of whether the biopsy was from a study participant or not. All five skin biopsies from healthy controls "showed relatively even distribution of variegated sized unmyelinated axons sheathed well by complicatedly folded Schwann cell membranes." However, in the tissue samples from 9 of the 13 fibromyalgia petients, unmyelinated Schwann cells were noted to be ballooned, a finding not found in any of the controls.

Axons in most patients trended towards being localized in the periphery of the unmyelinated Schwann cell sheaths (p = 0.002). Particularly, peripheral localization of axon in the unmyelinated Schwann cell sheath had a strong relationship with ballooning of Schwann cell (p =0.042), simplified folding of Schwann cell sheath (p = 0.039) and smaller axon (p = 0.034). Myelinated nerve fibers were unremarkable.

Gender Differences in Fibromyalgia Patients' Medical and Social Experiences

Researchers in Spain set about evaluating the sociodemographic, clinical and psychosocial differences between men and women with fibromyalgia, as well as analyzing the differences in how fibromyalgia symptoms impact male and female patients in their daily activities and work environment, and how they are treated by the healthcare system. In this study, published in Revista Clínica Española [2007 Oct;207(9):433-9], they used a detailed survey, distributed to patients with currently diagnosed fibromyalgia in three different rheumatology clinics in Spain.

The sociodemographic characteristics were very similar in men and women. However, there was a greater proportion of men diagnosed with [fibromyalgia] on sick leave, compared to women with the same diagnosis. Men had a worse perception of their health, a higher percentage of psychiatric history and current mental illness and more impact of the disease.

Physical Activity Protects Men with PTSD from Developing Severe Fibromyalgia

Researchers at Meir Medical Center in Israel have discovered that men with combat-related post-traumatic stress disorder (PTSD) are less likely to develop severe fibromyalgia (FMS) if they maintain a high level of physical activity, according to a study published in Italy's Clinical and Experimental Rheumatology (2007 Jul-Aug;25(4):529-33).

Because fibromyalgia has been associated with some mental health disorders, and a recent study showed that fibromyalgia is more prevalent in men suffering from combat-related PTSD, the researchers chose to "analyze the relationship between engagement in physical activity, the psycho-metric traits of PTSD and the future development of FMS." They studied 55 male patients who had all been diagnosed with post-traumatic stress disorder after combat-related trauma. All were examined using the American College of Rheumatology (ACR) criteria to determine the presence or absence of fibromyalgia.

Each patient completed questionnaires characterizing his quality of sleep, and the Sheehan Disability Scale measuring performance in the familial, social and vocational spheres. Additionally, each of the enrollees was interviewed by an experienced psychiatrist, who then completed a Clinician Administered PTSD Scale, a Clinical Global Impression Scale, and calculated an SF-36 score. Each patient was asked whether he exercised often, occasionally or not at all.

Gender Differences in Chronic Pain and Depression Rates

In October's Psychosomatics (2007 Oct;48(5):394-399), Canadian researchers present results of an epidemiological study of "gender differences in the prevalence of depression in four chronic pain conditions and pain severity indices in a national database."

In 131,535 adults, the prevalence of depression in women (9.1%) was almost twice that of men (5%). One-third (32.8%) had a chronic pain condition (fibromyalgia, arthritis/rheumatism, back problems, and migraine headaches). The prevalence of depression in individuals with chronic pain conditions was 11.3%, versus 5.3% in those without. Women reported higher rates of chronic pain conditions and depression and higher pain severity than men.... Depression and chronic pain conditions represent significant sources of disability, especially for women.

Transcranial Magnetic Stimulation Induces Long-Term Pain Decrease in Fibromyalgia Patients

As we reported in this post from 2006, transcranial magnetic stimulation is increasingly being studied and found to be effective in pain reduction for fibromyalgia and other conditions. The latest study of transcranial magnetic stimulation comes from the journal Brain (2007 Sep 14) and details an experiment conducted by researchers in France. This study was based upon the premise that "non-invasive unilateral repetitive transcranial magnetic stimulation (rTMS) of the motor cortex induces analgesic effects in focal chronic pain syndromes, probably by modifying central pain modulatory systems." Because neuroimaging studies have shown that a large number of brain structures, including those involved in pain processing, are activated during rTMS, the researchers purported that this type of stimulation could induce "generalized analgesic effects." They conducted their study with the goal of determining the effects of unilateral motor cortex-focused rTMS on 30 patients with chronic widespread fibromyalgia pain.

In this double-blind study, patients were randomly assigned to receive active rTMS or a sham treatment, both applied to the left primary motor cortex once a day for ten days. Outcome was measured primarily through self-reported pain intensity over the last 24 hours, which was measured before the study, daily during the treatments, and then 15, 30 and 60 days after the treatment sessions began. They also used other assessment tools such as the McGill Pain Questionnaire, Fibromyalgia Impact Questionnaire, Hamilton Depression Rating Scale, the Beck Depression Inventory and the Hospital Anxiety and Depression Scale. In addition, they tested the pain threshold of specific tenderpoints using applied pressure after rTMS treatments.

The study found that "[A]ctive rTMS significantly reduced pain and improved several aspects of quality of life (including fatigue, morning tiredness, general activity, walking and sleep) for up to 2 weeks after treatment had ended. The analgesic effects were observed from the fifth stimulation onwards and were not related to changes in mood or anxiety. The effects of rTMS were more long-lasting for affective than for sensory pain, suggesting differential effects on brain structures involved in pain perception."

They reported very few side effects and concluded that the data shows that unilateral rTMS of the motor cortex has potential as an effective analgesic therapy for fibromyalgia due to its long-term reduction of chronic widespread pain.

Researchers Suggest NDMA as "Possible Lynchpin" In the Pathogenesis of Fibromyalgia

In N-Methyl-D-Aspartate Receptor-Mediated Chronic Pain: New Approaches to Fibromyalgia Syndrome Etiology and Therapy, several researchers present their approach to the causation and therapy of fibromyalgia syndrome. Published in Journal of Musculoskeletal Pain (Vol 15, Issue 2, pp. 33 - 44), this article hypothesizes that FMS may be caused by "stress-induced disturbances of endocrine and neurological systems, involving the N-Methyl-D-Aspartate [NMDA] receptor." This receptor is implicated in other chronic pain conditions, as well. Their review aims to "provide evidence for targeting the NMDA receptor for FMS pharmacotherapy and discuss its significance to FMS pain."

The researchers found that fibromyalgia pain is difficult to manage effectively due to their being no "discrete objectifiable physical findings" and that psychological stress is often erroneously thought to be the sole explanation. In addition, the physical pathology of fibromyalgia pain is not yet clear. However, the authors posit that there is "an impressive body of evidence [that] suggests that FMS pain is likely due to central sensitization. Given its role in central pain perception and processing, the NMDA receptor represents a possible lynchpin in the pathogenesis of chronic pain in FMS." They write:

We propose that the very centrality of NMDA receptors in chronic pain makes them an ideal target for pharmacotherapy in FMS. Reports of recent clinical trials using newer low-affinity NMDA receptor antagonists have shown analgesic affects in chronic pain states other than FMS. These new compounds represent novel avenues of research into the management of chronic pain.

PET Scans Show Multidisciplinary Treatment May Alleviate Neurological Malfunctioning in Fibromyalgia

The results of a pilot study published in Rheumatology International (July 20, 2007) show that clinical improvement in fibromyalgia can occur when a multi-disciplinary treatment program is able to increase a fibromyalgia patient's limbic metabolism. According to researchers at Washington Hospital Center, Washington, DC, this indicates that there is limbic system involvement in fibromyalgia syndrome.

Aberrant central neurological functioning is believed to contribute to the abnormal sensations of fibromyalgia (FM). This pilot study sought to determine if alterations in regional brain metabolism from baseline occur in FM after undergoing a multidisciplinary therapeutic regimen. Regional brain metabolic activity was estimated using (18)F-fluorodeoxyglucose positron emission tomography ((18)FDG PET). Nine participants with FM received an 8-week comprehensive treatment program. Serial testing with (18)FDG PET and the Fibromyalgia Impact Questionnaire were performed. Statistical analysis was performed using repeated Wilcoxon signed rank tests. A clinical improvement (FIQ median change 20.68, P = 0.005) was noted with treatment. With treatment, increases in brain metabolism were noted in various components of the limbic system (P = 0.004-0.1). An increase in limbic metabolism was noted with concomitant symptomatic improvement, suggesting that the limbic system attenuates FM symptoms.