FibroAction News Feed

The role of central dopamine

Fri, 30 May 2008 12:00:00 +0100

Dr Patrick Wood MD has had an article published in the May edition of the journal Expert Review of Neurotherapeutics in which he discusses the role of central dopamine in pain and analgesia [1].

Dr Wood is a respected authority on the cause and treatment of Fibromyalgia Syndrome (Fibro), who has twice been recognised by the American National Institutes of Health for his innovative research. He is Chief Medical Officer for Angler Biomedical Technologies, a private company whose primary focus is improving the understanding and treatment of fibromyalgia, and he formerly directed the Fibromyalgia Research Program and Fibromyalgia Care Clinic at Louisiana State University. Dr Wood is the originator of the Dopamine Theory of Fibromyalgia and he spearheaded the use of advanced imaging technologies, including Positron Emission Tomography (PET scans) and Magnetic Resonance Spectroscopy (MRI) to investigate fundamental changes within the central nervous system relating to Fibro. [2]

In the article, Dr Wood says that recent insights have shown that dopamine has a central role in modulating pain perception and natural analgesia within parts of the brain. Also, while the role of the neurotransmitters, serotonin and norepinephrine, in inhibiting pain (through spinal descending inhibition) is well known, it has now been shown that dopamine has a critical role in this respect too.

Decreased levels of dopamine likely contribute to the painful symptoms that frequently occur in Parkinson's disease and Dr Wood notes that abnormalities in dopamine related neurotransmission have been found in other painful clinical conditions, including burning mouth syndrome, fibromyalgia syndrome and restless legs syndrome. Evidence from animal models and indirect evidence from pharmaceutical trials apparently also suggests a role for dopamine in chronic regional pain syndrome and painful diabetic neuropathy.

The Dopamine Theory of Fibromyalgia, which Dr Wood instigated, proposes that a combination of genetic and environmental factors, such as stress and trauma, causes a reduction in the production of dopamine in the brain of people with Fibromyalgia Syndrome and the reduced levels of dopamine then go on to cause other abonormalities and cause the symptoms of Fibromyalgia Syndrome. [3]

Studies carried out by Dr Wood and his colleagues have shown that people with Fibromyalgia Syndrome have both reduced dopamine activity in the central nervous system [4] and an abnormal dopamine response to pain [5] where people with Fibromyalgia Syndrome do not release dopamine in response to pain, meaning that pain stimuli are felt as being more painful than for healthy controls.

Dr Wood says that several new classes of medication with analgesic properties have an effect on dopamine, as is shown by the capacity of dopamine antagonists to reduce their analgesic capacity. [1] The dopamine agonist, Pramipexole, has also been found to be extremely promising as a treatment for Fibromyalgia Syndrome and has been mostly studied by Dr Andrew Holman MD, who is based in Seattle. [6]

Dr Wood and Dr Holman both feature in the DVD 'Fibromyalgia: Show Me Where It Hurts' which discusses the Dopamine Theory of Fibromyalgia and the studies behind it.

In the DVD, Dr Holman says: "The study of fibromyalgia is doing so much to uncover new areas of human physiology, it’s almost unfathomable."

In the Expert Review of Neurotherapeutics article, Dr Wood says that: "An expanded appreciation for the role of dopamine in natural analgesia provides the impetus for further study ...which may lead to the development of novel therapeutic strategies."

The role of dopamine in Fibromyalgia Syndrome, the potential treatments relating to that and the knowledge that is being discovered in these studies is extremely exciting and could lead to more effective use of medications to treat Fibromyalgia Syndrome. Some doctors (mostly in the US, but including Professor John Davies at Guys Hospital, London) are already using medications that affect dopamine to treat Fibromyalgia Syndrome patients, with a promising level of success.

References:

Wood PB. Role of central dopamine in pain and analgesia. Expert Rev Neurother. 2008 May;8(5):781-97.
Kuchinad A, Schweinhardt P, Seminowicz DA, Wood PB, Chizh BA, Bushnell MC. Accelerated brain gray matter loss in fibromyalgia patients: premature aging of the brain? J Neurosci. 2007 Apr 11;27(15):4004-7.
Wood PB. Stress and dopamine: implications for the pathophysiology of chronic widespread pain. Med Hypotheses. 2004;62(3):420-4.
Wood PB, Patterson JC 2nd, Sunderland JJ, Tainter KH, Glabus MF, Lilien DL. Reduced presynaptic dopamine activity in fibromyalgia syndrome demonstrated with positron emission tomography: a pilot study. J Pain. 2007 Jan;8(1):51-8. Epub 2006 Oct 4.
Wood PB, Schweinhardt P, Jaeger E, Dagher A, Hakyemez H, Rabiner EA, Bushnell MC, Chizh BA. Fibromyalgia patients show an abnormal dopamine response to pain. Eur J Neurosci. 2007 Jun;25(12):3576-82.
Holman AJ, Myers RR. A randomized, double-blind, placebo-controlled trial of pramipexole, a dopamine agonist, in patients with fibromyalgia receiving concomitant medications. Arthritis Rheum. 2005 Aug;52(8):2495-505.

Fibromyalgia and normalising behaviours

Fri, 30 May 2008 12:00:00 +0100

A new study has reported that Fibromyalgia Syndrome patients may not seek help to manage their symptoms because the symptoms seem normal to them. [1]

Fibromyalgia Syndrome often takes a long time to diagnose, with some patients even reporting that they had symptoms for decades before diagnosis. The attitudes and actions of the healthcare professionals seen by the patient are obviously involved in this delay, but so too can be patient attitudes and actions. A problem with invisible illnesses, such as Fibromyalgia Syndrome, which have no outward sign of illness, is that even the patient can doubt whether the symptoms are really there. The symptoms of Fibromyalgia Syndrome have been shown in research to have a number of physiological causes, but with nothing visible, some patients end up wondering if everyone feels the same as them. Many patients try to lead a normal life for some time after the onset of Fibromyalgia Syndrome, maintaining careers, relationships and lifestyles as far as possible for as long as they physically can, despite the immense struggle this can be. This struggle to remain “normal” can continue after diagnosis.

The study, carried out by a Turkish doctor, investigated whether Fibromyalgia Syndrome sufferers who didn’t seek medical help had a different level of normalising attributes than patients who sought medical help. Thirty-seven Fibromyalgia Syndrome patients who were seeing consultants about their condition were compared with 38 Fibromyalgia Syndrome sufferers who weren’t seeing a doctor, as well as 34 healthy controls. They were assessed for anxiety, depression, alexithymia (a relatively new term meaning the inability to express feelings in words) and normalising attributes.

The Fibromyalgia Syndrome sufferers who weren’t seeing a doctor were found to have the highest normalizing scores, with the Fibromyalgia Syndrome patients who were seeing a doctor having even lower normalizing scores than the healthy controls.

The article concluded that “normalization may negatively influence help-seeking behavior and contribute to non-help-seeking behavior.”

Reference:

Gulec H. Normalizing Attributions May Contribute to Non-Help-Seeking Behavior in People With Fibromyalgia Syndrome. Psychosomatics. 2008 May;49(3):212-217.

Myofascial Trigger Points In Whiplash Patients

Sun, 08 Jun 2008 12:00:00 +0100

Swiss researchers from the Reha Rheinfelden Rehabilitation Center and the Department of Neurology, University Hospital Basel, have had an article e-published ahead of print in the journal Archives of physical medicine and rehabilitation in which they describe a study that found a distinct pattern of myofascial findings in patients after whiplash injury. [1]

The objective of the study was to identify objective clinical signs for the diagnosis of whiplash syndrome, focusing on myofascial trigger points. Twenty-four healthy controls and 124 patients took part, including 47 patients with whiplash-associated disorders, 21 with Fibromyalgia Syndrome, 17 with nontraumatic chronic cervical syndrome and 15 with endogenous depression. Each participant was manually examined for myofascial trigger points of the semispinalis capitis, trapezius pars descendens, levator scapulae, scalenus medius, sternocleidomastoideus, and masseter muscles bilaterally.

The study found that 40 of the patients with whiplash (85.1%) had myofascial trigger points in the semispinalis capitis muscle, which was a significantly higher prevalence than any of the control groups (P

The researchers concluded that:

"Patients with whiplash showed a distinct pattern of trigger point distribution that differed significantly from other patient groups and healthy subjects. The semispinalis capitis muscle was more frequently affected by trigger points in patients with whiplash, whereas other neck and shoulder muscles and the masseter muscle did not differentiate between patients with whiplash and patients with nontraumatic chronic cervical syndrome or fibromyalgia."

Myofascial pain frequently co-exists with Fibromyalgia Syndrome, but it often unrecognised and left untreated [2]. It is important that Fibromyalgia Syndrome patients are checked out for myofascial problems, especially if they mention localised pain patterns and localised reductions in mobility. The results of this study suggest that it is even more important to check out patients with a whiplash injury for myofascial problems. The study also suggests that examinations for trigger points could be a way of differentiating between whiplash and other conditions that could give similar symptoms.

References:

Ettlin T, Schuster C, Stoffel R, Brüderlin A, Kischka U. A Distinct Pattern of Myofascial Findings in Patients After Whiplash Injury. Arch Phys Med Rehabil. 2008 Jun 3. [Epub ahead of print]

Starlanyl DJ, Copeland ME. Fibromyalgia and Chronic Myofascial Pain Syndrome: A Survival Manual. New Harbinger Publications: 2001.

Pregabalin for Fibromyalgia Syndrome

Tue, 10 Jun 2008 12:00:00 +0100

Researchers from the University of Cincinnati College of Medicine, Ohio, USA e-published an article on June 2nd, ahead of the print in the Journal of Pain, discussing a 14 week trial of pregabalin in patients with Fibromyalgia Syndrome. [1]

In 2007, Pregabalin (brand name Lyrica) was the first medication to be approved by the American Food and Drug Administration (FDA) for "on-label" use as a treatment for Fibromyalgia Syndrome.

Some of the researchers involved in the latest study were also involved in a 13 week Phase III trial of Pregabalin for Fibromyalgia Syndrome that was reported in the Journal of Rheumatology earlier this year. [2]

Both of these randomised, double-blinded, placebo-controlled trials aimed to assess the efficacy and safety of pregabalin in patients with Fibromyalgia Syndrome. They both used end point mean pain scores (as derived from daily diary ratings of pain intensity on an 0 to 10 scale) as the primary outcome variable, with other outcome variables being the Patient Global Impression of Change (PGIC) and the Fibromyalgia Impact Questionnaire (FIQ) total score. Other variables considered were assessments of sleep, fatigue, and mood disturbance. [1][2]

In the latest trial, 750 patients meeting American College of Rheumatology criteria for Fibromyalgia Syndrome had 1 week of single-blinded administration of placebo. After this, the participants were randomly pregabalin (at doses of 300 mg/d, 450 mg/d and 600 mg/d) or placebo, administered twice daily for 14 weeks. [1]

The trial found that, mean changes in pain scores at the end point in pregabalin-treated patients were significantly greater (P < .001: 300 mg/d, -0.71; 450 mg/d, -0.98; 600 mg/d, -1.00), compared with placebo-treated patients. Compared with placebo, significantly more pregabalin-treated patients reported improvement on PGIC (P < .01 for all 3 pregabalin doses) and significant improvements in total FIQ score for the 450 mg/d (P = .004) and the 600 mg/d (P = .003) doses. Compared with placebo, all 3 doses of pregabalin were associated with significant improvement in sleep. [1] This mainly reflects the findings of the Phase III trial [2], except that in that trial, improvements in FIQ-Total Score for the pregabalin groups were numerically but not significantly greater than those for the placebo group.

The most commonly reported pregabalin-related adverse events in both trials were dizziness and somnolence, which tended to be dose-related. [1][2]

The researchers from the latest trial said that:

"This randomized, placebo-controlled trial of 300, 450, and 600 mg/d of pregabalin monotherapy demonstrated that all 3 doses were efficacious for up to 14 weeks for the treatment of fibromyalgia and were well tolerated by most patients. These results provide evidence that pregabalin is an important treatment option for patients with fibromyalgia."

Some of the researchers involved in both trials were also involved in a 6 month trial to evaluate the efficacy of pregabalin monotherapy for durability of effect on the pain from Fibromyalgia Syndrome, the results of which were published in the June edition of the journal pain. [3]

This trial started with a 6-week open-label pregabalin-treatment period, where, during weeks 1-3, 1051 patients received escalating dosages of pregabalin to determine their optimal dosages and, during weeks 4-6, patients received their optimal fixed dosages (either 300, 450 or 600mg/d). To be randomised, patients must have had 50% decrease in pain Visual Analogue Score and a self-rating of "much" or "very much" improved on Patient Global Impression of Change (PGIC) at the end of this 6-week period. [3]

There then followed a 26-week double-blinded trial with participants receiving either placebo (287 partcipants) or their optimal fixed dosage of pregabalin (279 participants). The primary outcome was time to loss of therapeutic response (LTR), defined as a less than 30% reduction in pain (from the open-label baseline) or worsening of the Fibromyalgia Syndrome. [3]

The trial found that time to LTR was longer for pregabalin versus placebo (P<.0001) and that, whereas half the placebo group had LTR by Day 19, half the pregabalin group still had not lost response by the end of the trial. At the end of the trial, 174 (61%) placebo patients met LTR criteria versus 90 (32%) pregabalin patients. [3]

The researchers considered that pregabalin was well tolerated, though 178 (17%) discontinued during the open-label stage for treatment-related adverse events, and more pregabalin than placebo patients discontinued for adverse events during the doubled-blinded stage. [3]

The researchers concluded that:

"In those who respond, pregabalin demonstrated durability of effect for relieving FM pain."

In the trial described above, 54% of initial participants made it through the open-label stage and achieved 50% decrease in pain on the Visual Analogue Score and a self-rating of "much" or "very much" improved on the Patient Global Impression of Change. [3]

When the FDA approved pregabalin (Lyrica) for the treatment of Fibromyalgia Syndrome, Steven Galson MD MPH, director of the FDA's Center for Drug Evaluation and Research, cautioned that the drug was not a panacea because response to the drug was not universal. [4]

Response rates to pregabalin in patients with Fibromyalgia Syndrome have varied widely [4] meaning that, although for some patients Pregabalin is an efficient and well tolerated treatment, there are quite a large proportion of Fibromyalgia Syndrome patients who either do not respond or who suffer from adverse side effects.

References:

Arnold LM, Russell IJ, Diri EW, Duan WR, Young JP Jr, Sharma U, Martin SA, Barrett JA, Haig G. A 14-week, Randomized, Double-Blinded, Placebo-Controlled Monotherapy Trial of Pregabalin in Patients With Fibromyalgia. J Pain. 2008 Jun 2. [Epub ahead of print]

Mease PJ, Russell IJ, Arnold LM, Florian H, Young JP Jr, Martin SA, Sharma U. A randomized, double-blind, placebo-controlled, phase III trial of pregabalin in the treatment of patients with fibromyalgia. J Rheumatol. 2008 Mar;35(3):502-14. Epub 2008 Feb 15.

Crofford LJ, Mease PJ, Simpson SL, Young JP Jr, Martin SA, Haig GM, Sharma U. Fibromyalgia relapse evaluation and efficacy for durability of meaningful relief (FREEDOM): a 6-month, double-blind, placebo-controlled trial with pregabalin. Pain. 2008 Jun;136(3):419-31. Epub 2008 Apr 8.

Peck P. Pregabalin (Lyrica) Is First Drug Approved for Fibromyalgia. June 22, 2007. MedPage Today. http://www.medpagetoday.com/ProductAlert/Prescriptions/tb/5992

Cannabinoids for Fibromyalgia Syndrome

Tue, 10 Jun 2008 12:00:00 +0100

An article has been e-published ahead of print in the journal Nature Clinical Practice. Rheumatology by Fibromyalgia Syndrome expert, Dr Roland Staud MD, and EB Koo, an undergraduate student at the University of Florida, discussing whether cannabinoids are a new treatment option for Fibromyalgia Syndrome. [1] Dr Staud, author of 'Fibromyalgia for Dummies', is Professor of Medicine at the College of Medicine and Director of the Center for Musculoskeletal Pain Research at the University of Florida.

The article discusses cannabinoids as a treatment option for Fibromyalgia Syndrome in light of the study by Skrabek et al, discussed in an article in the February issue of the Journal of Pain. [2]

Skrabek et al carried out what was apparently the first randomized, controlled trial to assess the benefit of nabilone, a synthetic cannabinoid, on pain reduction and quality of life improvement in patients with Fibromyalgia Syndrome. [2]

The randomized, double-blind, placebo-controlled trial was carried out on 40 patients with Fibromyalgia Syndrome. The primary outcome measure, visual analog scale (VAS) for pain, and the secondary outcome measures, number of tender points, the average tender point pain threshold, and the Fibromyalgia Impact Questionnaire (FIQ), were evaluated at 2 and 4 weeks into the trial and then again after a 4-week washout period. [2]

Skrabek et al's trial found that there were significant decreases in the VAS (-2.04, P < .02), FIQ (-12.07, P < .02), and anxiety (-1.67, P < .02) in the nabilone treated group at 4 weeks, and that after the 4-week wash-out period, all benefits were lost, with the nabilone treated group returning to their baseline levels of pain and quality of life. There were no significant improvements in the placebo group. The treatment group experienced more side effects per person at 2 and 4 weeks (1.58, P < .02 and 1.54, P < .05), respectively, and although nabilone was not associated with serious adverse effects, some patients did experience drowsiness, dry mouth, vertigo and ataxia. [2]

Skrabek et al said that:

"Nabilone appears to be a beneficial, well-tolerated treatment option for fibromyalgia patients, with significant benefits in pain relief and functional improvement. ... As nabilone improved symptoms and was well-tolerated, it may be a useful adjunct for pain management in fibromyalgia."

Nabilone, a synthetic cannabinoid, is used to treat chemotherapy-induced nausea and vomiting in patients who do not respond well to other anti-emetics. However, it has also been studied for use in treating cancer pain and neuropathic pain.

Cannabinoids are chemicals that are structurally similar to cannabis or THC (the main psychoactive substance found in cannabis), or that bind to cannabinoid receptors.

References:

Staud R, Koo EB. Are cannabinoids a new treatment option for pain in patients with fibromyalgia? Nat Clin Pract Rheumatol. 2008 Jun 3. [Epub ahead of print].

Skrabek RQ, Galimova L, Ethans K, Perry D. Nabilone for the treatment of pain in fibromyalgia. J Pain. 2008 Feb;9(2):164-73. Epub 2007 Nov 5.

Fibromyalgia in Post Menopausal Women

Sun, 15 Jun 2008 12:00:00 +0100

A medication to help prevent osteoporosis and invasive breast cancer in post-menopausal women may also help those who have Fibromyalgia Syndrome (Fibro), according to a recently published study. [1]

The article, from a group of Iranian researchers, was published in the July edition of the European journal of internal medicine (e-published last November), and discusses a study looking at Raloxifene (Evista) in the treatment of Fibro.

Raloxifene is a type of medication called a selective oestrogen receptor modulator. It is licensed in the USA and UK for the treatment of osteoporosis in post-menopausal women and also for the prevention of invasive cancer in post-menopausal women who either have osteoporosis or are at high risk of invasive breast cancer. Raloxifene is not a form of Hormone Replacement Therapy (HRT), but is rather an oestrogen agonist/antagonist, which means that it works like oestrogen in some tissues in the body, and has the opposite effect in other tissues.

The double-blind randomized study was carried out from Feb 2005 until Oct 2006 and enrolled one hundred menopausal women with Fibro. Fifty study participants were given Raloxifen 60mg every other day over 16 weeks, with the other 50 being given a placebo. [1]

The primary outcome measure used was a mean score from: the Stanford Health Assessment Questionnaire (HAQ); the Iranian version of Hospital Anxiety and Depression questionnaire (IHAD); sleep disturbance; number of tender points; and the reduction of pain and fatigue based on Visual Analogue Score (VAS).

Forty-nine (98%) of the participants receiving Raloxifen and 47 (94%) of the participants receiving placebo completed the study. [1]

The study group taking the Raloxifen had a significantly higher response rate than the placebo group, with reduced pain and fatigue, reduced tender point count, reduced sleep disturbance and recovery of usual activities as measured by the Stanford Health Assessment Questionnaire (HAQ). No significant effect on the Hospital Anxiety and Depression questionnaire score was seen. [1]

The researchers concluded that:

"Raloxifen was superior to placebo in the treatment of menopausal patients with fibromyalgia." [1]

Anecdotal reports and some studies suggests that, although abnormalities in reproductive hormone levels are not associated with Fibro [2], the reproductive hormones may have an effect on Fibro symptoms, with the menopause worsening symptoms in some patients [3][4]. However, some studies have also suggested that the use of HRT, and specifically oestrogen HRT, may increase the risk of suffering from Fibro and other chronic pain conditions. [5][6][7] The selective modulation of oestrogen by Raloxifene, as opposed to the replacement of oestrogen by HRT, may be an important factor and could be a novel way of managing both some of the health risks associated with the menopause and also Fibro, in post-menopausal women with Fibromyalgia Syndrome.

References:

Sadreddini S, Molaeefard M, Noshad H, Ardalan M, Asadi A. Efficacy of Raloxifen in treatment of fibromyalgia in menopausal women. Eur J Intern Med. 2008 Jul;19(5):350-5. Epub 2007 Nov 28.
Samborski W, Sobieska M, Pieta P, Drews K, Brzosko M. Normal profile of sex hormones in women with primary fibromyalgia. Ann Acad Med Stetin. 2005;51(2):23-6.

Pamuk ON, Cakir N. The variation in chronic widespread pain and other symptoms in fibromyalgia patients. The effects of menses and menopause. Clin Exp Rheumatol. 2005 Nov-Dec;23(6):778-82.

Okifuji A, Turk DC. Sex hormones and pain in regularly menstruating women with fibromyalgia syndrome. J Pain. 2006 Nov;7(11):851-9.

Macfarlane TV, Blinkhorn A, Worthington HV, Davies RM, Macfarlane GJ. Sex hormonal factors and chronic widespread pain: a population study among women. Rheumatology (Oxford). 2002 Apr;41(4):454-7.

Benediktsdóttir B, Tómasson K, Gíslason T. [Climateric symptoms and hormone replacement treatment among 50 years old Icelandic women.] Laeknabladid. 2000 July/August;86(7/8):501-507.

Meisler JG. Chronic pain conditions in women. J Womens Health. 1999 Apr;8(3):313-20.

City of Hope Fibro Study

Wed, 25 Jun 2008 12:00:00 +0100

Dr. R. Paul St. Amand, Cladia Craig Marek, Dr John (Jack) Shively PhD and a team of researchers working on the "City of Hope Fibromyalgia Study" have e-published a paper ahead of print in the journal Experimental biology and medicine. [1]

Dr. R. Paul St. Amand is the originator of the Guaifenesin Protocol for Fibromyalgia Syndrome (Fibro), a much debated treatment protocol that is not widely accepted by the medical community. Claudia Craig Marek, his medical assistant, is the author of 'Fibromyalgia: The First Year'. The "City of Hope Fibromyalgia Study" is a three-year investigation involving patients of Dr St Amand, which is taking place at City of Hope Hospital in California, USA, where Dr Shively PhD is Chair of the Division of Immunology.

The purpose of the City of Hope Fibro study is to compare the blood of Fibro patients with that of healthy participitants in terms of autoinflammatory genes (genes involved with an inflammatory response when there is no obvious infection) and response to inflammatory stimuli. Other purposes are to determine if there are polymorphisms of the autoinflammatory genes and to look for evidence of links between Fibro and immune or genetic factors.

In the study discussed in the recently e-published article, blood plasma levels of 25 cytokines and chemokines in 92 female Fibro patients and 69 family members were measured, compared to 77 control samples taken from the City of Hope blood bank. The patient group included: patients whose parents did not have Fibro; patients who had one parent with Fibro; patients who had one parent with Fibro but a sibling that did not; and, in one case, a patient whose mother and maternal grandmother both had Fibro. Fifty-six (61%) of the patient group had been treated with the Guaifenesin Protocol for at least 3 months. [1] The control samples were known to be from females without Fibro, although it is not known how well they were screened for signs of the condition, or other conditions.

Cytokines are extensively within the body for communication between cells, like hormones and neurotransmitters, but with a greater diversity than either hormones (which are usually transported in the blood) or neurotransmitters (which are related to the nervous system). Cytokines are involved in the development and functioning of the immune system, as well as with a variety of immunological, inflammatory and infectious diseases. Chemokines are a group of small Cytokines, some of which are considered to promote inflammation.

The movement of leukocytes, a type of white blood cell, across membranes within the body, and the cytokine profile of skeletal muscle cells, were also analysed.

The study found that the Fibro patients and their family members had high levels of MCP-1 and eotaxin compared to controls. [1] However, it was not known how many of the family members might also have had Fibro themselves.

MCP-1, or Monocyte chemotactic protein-1, is a chemokine with a role in getting various immune system cells to the site of infection or injurys. Eotaxin is another chemokine, with a role in recruiting eosinophils, other immune system cells with a relation to inflammation, which are responsible for combating infection and parasites and also control mechanisms associated with allergy and asthma. MCP-1 and Eotaxin gene polymorphisms have been reported to contribute to susceptibility to several immune and inflammatory conditions.[2][3][4]

The City of Hope study article also said that they had found that the patient group on the Guaifenesin Protocol had higher levels of eotaxin than those not being treated. [1]

The article says that "[d]iluted plasma from patients increased the migration of normal eosinophils and monocytes, but not neutrophils, through an endothelial/Matrigel barrier only when mast cells are included in the lower wells". [1] In other words, when compared to the controls, the samples from Fibro patients increased the amount of eosinophils and monocytes crossing barriers similar to those surrounding the internal vessels of the body, such as blood vessels: i.e. they increased the rate of movement of eosinophils and monocytes.

The study also found that skeletal muscle cells can, when tested in the laboratory (in vitro), secrete MCP-1, eotaxin, and IP-10, while treatment with MCP-1 caused secretion of IL-1beta, eotaxin and IP-10 (another cytokine). [1]

In the discussion, the researchers note that there are some possibly conflicting findings in their results, notably the raised levels of both MCP-1 and eotaxin. As eotaxin is a natural antagonist for the main receptor (CCR2) for MCP-1, the raised levels of eotaxin may be in response to the high levels of MCP-1 found, as the body tries to offset the damage caused by the MCP-1. This could also explain the high levels of IP-10 found, as IP-10 is the natural antagonist for both MCP-1 and eotaxin.

The researchers concluded that:

"the [Fibro group] studied here is associated with elevated levels of inflammatory chemokines, MCP-1 and eotaxin may contribute to the symptoms of [Fibro], parents of these patients share the expression profile, and [muscle cells] are a potential source of eotaxin and MCP-1. Therefore reduction of eotaxin and MCP-1 levels or blockade of their receptors may be a reasonable treatment strategy for [Fibro]. We also found evidence that treatment with guifenesin accentuates eotaxin production and reduces IL-13 and IFN-gamma [(other cytokines/chemokines)]. While only a few studies have shown elevated cytokine levels in [Fibro], our data suggests that elevated chemokine levels may play a causative role in [Fibro] and should be investigated further."

However, Hellhammer et al [5] found that chronic stress, such as that experienced by chronic pain patients, e.g. Fibro patients, disrupts the HPA axis and leads to low levels of cortisol. In the long-term, the low cortisol levels may lead to increased levels of other substances, such as leukocytes and cytokines. [5] Thus it could be argued that the raised levels of cytokines found in the Fibro patients in this study may be caused by the Fibro, rather than causing the Fibro in the first place. Or it could be a chicken-and-egg situation where the one worsens the other, making the first worse, and it is very hard to separate cause from effect.

There may also be a fault in the way the results are compared, which would mean that the raised levels of eotaxin in the patient group on the Guaifenesin Protocol compared to the patient group not on Guaifenesin may not be significant.

In summary, the study found that people with Fibro, whether they were on the Guaifenesin protocol or not, had high levels of substances that are usually associated with autoimmune and inflammatory conditions, suggesting that they may be an inflammatory or autoimmune connection with Fibro. Family members of the Fibro patients also had raised levels of some of these substances, suggesting that Fibro might have a family or genetic link. Dr St Amand has suggested that the raised levels of one of the immune system substances found in the patients on the Guaifenesin Protocol, as opposed to those who were not, may be of significance for the validity of the Guaifenesin Protocol. However, there were some flaws in the study and possibly in the conclusion, such as it not being known whether the family members themselves had Fibro and the difference between the Fibro patients on the Guaifenesin Protocol and those who were not, not in itself being significant.

This study remains a very interesting piece of research, but its significance may unfortunately be diluted by the flaws in the study and its significance to proponents of the Guaifenesin Protocol as evidence of the protocol is debatable.

References:

Zhang Z, Cherryholmes G, Mao A, Marek C, Longmate J, Kalos M, St Amand RP, Shively JE. High plasma levels of MCP-1 and eotaxin provide evidence for an immunological basis of fibromyalgia. Exp Biol Med (Maywood). 2008 Jun 5. [Epub ahead of print]
Amoli MM, Salway F, Zeggini E, Ollier WE, Gonzalez-Gay MA. MCP-1 gene haplotype association in biopsy proven giant cell arteritis. J Rheumatol. 2005 Mar;32(3):507-10.
Chae SC, Park YR, Shim SC, Lee IK, Chung HT. Eotaxin-3 gene polymorphisms are associated with rheumatoid arthritis in a Korean population. Hum Immunol. 2005 Mar;66(3):314-20.
Bugeja MJ, Booth D, Bennetts B, Heard R, Rubio J, Stewart G. An investigation of polymorphisms in the 17q11.2-12 CC chemokine gene cluster for association with multiple sclerosis in Australians. BMC Med Genet. 2006 Jul 26;7:64.
Hellhammer DH, Ehlert U, Heim C. The potential role of hypocortisolism in the pathophysiology of stress-related bodily disorders. Psychoneuroendocrinology 25 (2000) 1–35

Fibrofog mimics 20 years of aging

Sun, 29 Jun 2008 12:00:00 +0100

An article has been published recently suggesting that the cognitive problems associated with Fibrofog mimic around 20 years of aging. [1]

The article, Fibromyalgia and cognition, by JM Glass, was published in the Journal of clinical psychiatry.

Cognitive difficulties are a common symptom of Fibromyalgia Syndrome (Fibro), including problems with memory and difficulty concentrating. These cognitive difficulties are often nicknamed "Fibrofog". The existence of these symptoms has been confirmed, according to the article, by studies that were looking at the incidence of cognitive problems in Fibro patients. These studies included objective tests of metamemory (knowing about your own memories, such as how accurate they are), working (short-term) memory, semantic memory (such as remembering facts and the meanings of words), everyday attention, task switching (i.e. being able to change from one task to another), and selective attention (when you purposely focus on one thing). The studies show that the problems with working (short-term) memory, episodic (relating to a specific event) memory and semantic memory associated with Fibro mimic the effects of around 20 years of aging. [1]

According to the article, the cognitive difficulties associated with Fibro may be exacerbated by the presence of depression, anxiety, sleep problems, endocrine disturbances, and pain, but the relationship of these factors to the cognitive difficulties is unclear. [1]

Glass notes that standardised tests and treatment have not yet been established for the cognitive difficulties associated with Fibro. [1] These cognitive difficulties can be extremely hard for patients to cope with and they can have a significant impact on Fibro patients' ability to function and especially to continue working. Proving the cognitive difficulties is often complicated and this can cause issues with family and carers, employers and benefits agencies. Standardised testing for these cognitive problems would be useful and could provide validation for patients. Having accepted treatment protocols for "Fibrofog" would likely make a huge difference to the impact Fibro can have on patients' lives.

References:

Glass JM. Fibromyalgia and cognition. J Clin Psychiatry. 2008;69 Suppl 2:20-4.

An Internet based Self Management Program

Mon, 30 Jun 2008 12:00:00 +0100

An internet based Self Management Program can help people with Fibromyalgia Syndrome (Fibro) or arthritis, according to a recent article. [1]

The article, by a group of researchers at Stanford University School of Medicine, California, USA, was recently e-published ahead of print in the journal Arthritis and Rheumatism. In it, they discuss the results of a 1-year trial of an internet-based arthritis self-management program for patients with arthritis or Fibro.

The researchers note that small-group arthritis self-management programs have proven effective in changing health-related behaviors and improving health status measures. The study specifically aimed to determine the efficacy of an Internet-based Arthritis Self-Management Program as a resource for patients who were either unable or unwilling to attend such a small-group program. [1]

For the study, 855 patients with either rheumatoid arthritis, osteoarthritis, or Fibro, and Internet and e-mail access, were randomized to an intervention or usual care control group. Outcome measures included 6 health status variables (pain, fatigue, activity limitation, health distress, disability, and self-reported global health), 4 health behaviors (aerobic exercise, stretching and strengthening exercise, practice of stress management, and communication with physicians), 5 utilization variables (physician visits, emergency room visits, chiropractic visits, physical therapist visits, and nights in hospital), and self-efficacy. The participants assigned to the intervention group were compared with usual care controls at 6 months and 1 year.

At 1 year, the group assigned to the internet based Arthritis Self Management Program had significantly improved in 4 of 6 health status measures and self-efficacy. No significant differences in health behaviors or health care utilization were found. [1]

The researchers concluded that:

"The Internet-based [Arthritis Self-Management Program] proved effective in improving health status measures at 1 year and is a viable alternative to the small-group [Arthritis Self-Management Program]." [1]

Variations on the Expert Patient Program are used in many countries as a means of helping patients with chronic illnesses. However, having to attend regular meetings often puts some people off, especially those with more severe conditions. The use of an Internet based self-management program could be very useful to a number of patients.

References:

Lorig KR, Ritter PL, Laurent DD, Plant K. The internet-based arthritis self-management program: A one-year randomized trial for patients with arthritis or fibromyalgia. Arthritis Rheum. 2008 Jun 24;59(7):1009-1017. [Epub ahead of print]

Sleep disturbances and Fibro

Mon, 30 Jun 2008 12:00:00 +0100

A recent article discusses a study that looked at the relationship between sleep problems, pain, depression, and physical functioning in patients with Fibromyalgia Syndrome (Fibro). [1]

The article, Sleep disturbances in fibromyalgia syndrome: Relationship to pain and depression, from researchers at Indiana University and Purdue University, Indianapolis, USA, was e-published ahead of print in the journal Arthritis and Rheumatism.

The study involved a baseline assessment and then 1-year follow up of Fibro patients, diagnosed according to the 1990 ACR criteria. who were recruited from a Southern California health maintenance organization. Measures used to evaluate sleep, pain, depression, and physical functioning included the Center for Epidemiologic Studies Depression Scale, the McGill Pain Questionnaire, the Pittsburgh Sleep Quality Index, and the Fibromyalgia Impact Questionnaire. Six hundred patients completed the baseline assessment and 492 completed the 1-year assessment. [1]

The majority of the participants (96% at baseline and 94.7% at 1 year) were found to have problems sleeping. The results were analysed to find if there was a link between any of the variables at the baseline measurement and a change in another variable at the 1-year measurement. No variable was found to be significantly linked to a worsening of sleep problems, but poor sleep at the baseline measurement was linked to more pain at the 1-year measurement. More pain at the baseline measurement was also linked to poorer physical functioning at the 1-year measurement, and poorer physical functioning at the baseline measurement was linked to higher depression scores at the 1-year measurement. [1]

The researchers concluded that:

"These findings highlight the high prevalence of sleep problems in this population and suggest that they play a critical role in exacerbating [Fibromyalgia Syndrome] symptoms. Furthermore, they support limited existing findings that sleep predicts subsequent pain in this [the Fibro patient] population, but also extend the literature, suggesting that sleep may be related to depression through pain and physical functioning." [1]

This study is interesting in that, as well as highlighting how prevalent sleep problems are with Fibro, it also suggests a pathway for the development of depression as a result of Fibro. It is often thought that many Fibro patients have symptoms of depression, but it is not always considered whether problems due to the Fibro were the direct cause of the depression. [2] This study suggests that this is so, corroborating many anecdotal reports that depression is a result of Fibro. [1]

Fibro patients need to keep in mind that a lack of restorative sleep, no matter how much sleep is got overall, is in itself a sleep problem. When you could sleep for much of the day, it can seem unintuitive to say that you have a problem sleeping, but the lack of restorative sleep was one of the first recorded symptoms of Fibro. [3] And as this study suggests, poor sleep can lead to more pain, which can then lead to further problems. [1]

References:

Bigatti SM, Hernandez AM, Cronan TA, Rand KL. Sleep disturbances in fibromyalgia syndrome: Relationship to pain and depression. Arthritis Rheum. 2008 Jun 24;59(7):961-967. [Epub ahead of print]

Arnold LM. Management of fibromyalgia and comorbid psychiatric disorders. J Clin Psychiatry. 2008;69 Suppl 2:14-9.

Moldofsky H. Sleep and fibrositis syndrome. Rheum Dis Clin North Am. 1989 Feb;15(1):91-103.

Another aspect of Fibrofog measured

Mon, 21 Jul 2008 12:00:00 +0100

People with Fibromyalgia Syndrome (Fibro) have trouble reading words and naming colours quickly, according to a recently published article. [1] This is yet another aspect of the cognitive difficulties, nicknamed "Fibrofog", experienced by Fibro patients, that has actually been measured.

The article, e-published ahead of print in the Journal of Clinical Rheumatology, discusses a study carried by 2 researchers at Rush Medical College, Chicago, USA, that aimed to examine the speed of mental operations in people with Fibro under the pressure of time. [1]

The study involved 67 Fibro patients with a history of memory complaints and 51 controls without Fibro presenting with complaints of memory loss. They were asked to carry out 10 timed tasks designed to measure various aspects of the brain's processing speed. [1]

The researchers found that the majority (more than 70%) of the Fibro patients were not significantly different to the norm in performing 7 or more of the tasks. However, more than 49% of FMS patients tested as impaired on the specific tasks of reading words and naming colours. Compared with controls, the number of FMS patients showing impairment was 2.0 times greater for reading speed, and 1.6 times greater for color naming speed. The time delays involved were small, with an average time delay of 203 milliseconds for reading words and 285 milliseconds for naming colors, but these delays represent a significant increase in the time taken: 48% increase in time for Fibro patients to read the same stimulus word as controls. [1]

The researchers concluded that:

"Abnormalities in naming speed are an unappreciated feature of [Fibro]." [1]

They also concluded that abnormalities in naming speed, associated with otherwise good processing speeds, set Fibro patients apart from those with memory complaints but not Fibro. The researchers go on to suggest that clinicians request adding a rapid naming test (such as the Stroop Test) to the battery of cognitive tests in order to show up "cognitive dysfunction in [Fibro] patients who otherwise appear to test normally, despite often intense complaints of memory and concentration difficulties that can affect job performance and increase disability". [1]

An article published last month suggested that the cognitive problems associated with Fibrofog mimic around 20 years of aging. The author of that article noted that standardised tests and treatment have not yet been established for the cognitive difficulties associated with Fibro. [2] This new study suggests one test at least that could be a good cognitive test for Fibro, if not so much a measure of the severity of cognitive symptoms.

References:

Leavitt F, Katz RS. Speed of Mental Operations in Fibromyalgia: A Selective Naming Speed Deficit. J Clin Rheumatol. 2008 Jul 17. [Epub ahead of print]

Glass JM. Fibromyalgia and cognition. J Clin Psychiatry. 2008;69 Suppl 2:20-4.

GPs can treat Fibro just as well as consultants

Tue, 22 Jul 2008 12:00:00 +0100

Fibromyalgia Syndrome (Fibro) can be treated within the primary care setting, and getting treatment quickly leads to better outcomes, according to an article recently e-published ahead of print in the journal Arthritis Research & Therapy. [1]

The study aimed to compare the efficacy of the treatments for Fibro available in both primary care and specialised settings, as well as to look at variables that improve the outcome of treatment. [1] Primary care would normally be medical care with a GP, and specialised care would be with a specialist clinic or a hospital consultant.

The researchers looked at reports of randomized controlled trials researching pharmacological and non-pharmacological treatments for Fibro, available in the research resources MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials, and PsychInfo, with the most recent electronic search being carried out in June 2006. Of the 594 articles identified by abstract and title, 102 full articles were retrieved and 33 of these met the inclusion criteria. These randomised controlled trials assessed 120 treatment interventions on 7789 patients diagnosed with primary Fibromyalgia Syndrome, of which 4505 (57.8%) were included in the primary care group and 3284 (42.2%) in the specialised intervention group. The patients were mostly middle-aged women who had been suffering from Fibro for 6-10 years. [1]

The researchers found that the treatments used in the studies were on average effective, but that there was no significant difference in treatment efficiacy between the patients treated in a primary care setting and those treated in a specialised care setting. They concluded that there was no particular need for specialised care in treating Fibro. [1] The main factor affecting how efficient treatment for Fibro from different doctors is, is often how much knowledge of the condition they have. As Fibro does not fall properly into any one medical discipline, little training is given about the condition, even at consultant level. Primary care practitioners or General Practitioners (GPs) can therefore have as much information and knowledge as their more specialised colleagues.

The researchers also found that variables (that were not affected by the differences in the trials) that improved the outcome of patients receiving treatment were younger age of the patients and shorter duration of the disorder. In other words, the patients who were more likely to do well were young and hadn't been suffering from Fibro for very long. [1]

There were a number of issues with the trials used in this study, such as the varying quality of the trials and the different length of time the treatments were trialled impacting on the results. [1] The number of trials that fit the inclusion criteria was also relatively small.

Past studies have had mixed results as to whether duration of illness is a factor in how well Fibro patients respond to treatment. [2] However, anecdotal evidence suggests that on average, Fibro patients worsen over time, especially during the first few years of the condition. Timely treatment may mean that the condition is less severe, so that less improvement is needed to return the patient to a reasonable level of functionality and symptom relief. It may also make it less likely that reactive depression because of the Fibro develops [3] and psychiatric comorbidities negatively impact the severity and course of Fibro [4] so preventing these developing could lead to a better outcome for patients.

References:

Garcia-Campayo J, Magdalena J, Magallon R, Fernandez-Garcia E, Salas M, Andres E. Efficacy of fibromyalgia treatment according to level of care: a meta-analysis. Arthritis Res Ther. 2008 Jul 15;10(4):R81. [Epub ahead of print]

Wigers SH. Fibromyalgia outcome: the predictive values of symptom duration, physical activity, disability pension, and critical life events--a 4.5 year prospective study. J Psychosom Res. 1996 Sep;41(3):235-43.

Bigatti SM, Hernandez AM, Cronan TA, Rand KL. Sleep disturbances in fibromyalgia syndrome: Relationship to pain and depression. Arthritis Rheum. 2008 Jun 24;59(7):961-967. [Epub ahead of print]

Arnold LM. Management of fibromyalgia and comorbid psychiatric disorders. J Clin Psychiatry. 2008;69 Suppl 2:14-9.

Fibro is not the same as Major Depressive Disorder

Wed, 23 Jul 2008 12:00:00 +0100

A recent article says that Major Depressive Disorder (MDD) and Fibromyalgia Syndrome (Fibro) do not have the same underlying causes and are not subsets of the same disease concept, despite similarities between their characteristics and treatments. [1]

The article, which was e-published ahead of print in the journal Current medical research and opinion, reviewed research on the prevalence, etiology and pathogenesis, clinical characterization, and treatment of Fibro and MDD, as well as studies that examined the relationship between these disorders. The studies reviewed were identified via the PubMed literature search.

In discussing the objective of the review, the researchers said that:

"A large body of evidence suggests that the relationship between major depressive disorder (MDD) and [Fibro] is complex. Improved understanding of this relationship promises to provide clinicians with better assessment and treatment options for both disorders."

They found that there were substantial similarities between Fibro and MDD when considering neuroendocrine abnormalities, psychological characteristics, physical symptoms and treatments. However, they also found that "currently available findings do not support the assumption that MDD and FM refer to the same underlying construct or can be seen as subsidiaries of one disease concept."

The article concludes that new approaches may lead to a better understanding of the link betweem Fibro and MDD and also to more effective psychological and psychopharmacological therapies for Fibro. Medications that are also used as anti-depressants and anti-anxiety medications are already widely used as treatments for Fibro.

The researchers suggested that "clinicians should carefully screen for a history of MDD in patients with Fibro".

References:

Pae CU, Luyten P, Marks DM, Han C, Park SH, Patkar AA, Masand PS, Van Houdenhove B. The relationship between fibromyalgia and major depressive disorder: a comprehensive review. Curr Med Res Opin. 2008 Jul 4. [Epub ahead of print]

ATP calcium and magnesium levels in Fibro

Thu, 24 Jul 2008 12:00:00 +0100

A recent article from a group of Italian researchers has suggested that abnormal ATP levels within blood cells, along with disturbances in calcium and magnesium transport, may be a part of Fibromyalgia Syndrome (Fibro). [1]

The article, which was e-published ahead of print in the journal Clinical biochemistry, discusses a study in which the concentrations of ATP and positively charged ions (cations) were measured in 25 Fibro patients and 25 healthy controls through a chemiluminescent and a fluorimetric assay, respectively. The cation concentration was used as a measure of the concentration of calcium and magnesium, as these are present within cells as positively charged ions. [1]

ATP or Adenosine Triphosphate is a high energy a multifunctional nucleotide, whose most important function is the transport of chemical energy within cells for metabolism. It is the main energy source for the majority of cellular functions.

The preliminary study from the group of Italian researchers found that significantly lower ATP levels were observed inside the platelets of Fibro patients compared to the healthy controls. Fibro patients also showed a trend towards higher calcium concentrations in platelets, along with significantly increased magnesium levels. [1]

The researchers concluded that:

"This preliminary study suggests that disturbances in the homeostasis of platelet ATP metabolism-signaling and calcium-magnesium flows might have a relevance in the pathogenesis of [Fibro]." [1]

However, altered levels in intracellular levels have previously been associated with both aging and other conditions such as high blood pressure, so the results seen here in this preliminary study may be influenced by other factors. [2]

References:

Bazzichi L, Giannaccini G, Betti L, Fabbrini L, Schmid L, Palego L, Giacomelli C, Rossi A, Giusti L, De Feo F, Giuliano T, Mascia G, Bombardieri S, Lucacchini A. ATP, calcium and magnesium levels in platelets of patients with primary fibromyalgia. Clin Biochem. 2008 Jul 2. [Epub ahead of print]

Barbagallo M, Gupta RK, Dominguez LJ, Resnick LM. Cellular ionic alterations with age: relation to hypertension and diabetes. J Am Geriatr Soc. 2000 Sep;48(9):1111-6.

Online Group Lurkers may not get the most benefit

Sun, 27 Jul 2008 12:00:00 +0100

If you go to an online support group but "lurk" rather than participating, it may be preventing you from getting the most benefit out of the group, according to the recently published results of a Dutch study.

The study, results of which were published in the Journal of medical internet research, followed up on an earlier study that indicated that participation in online support groups had a profound effect on the participants’ feelings of “being empowered.” [1]

The earlier study, and indeed most previous studies of online patient support groups, focused on active members of these groups, who contribute by posting messages (posters). This new study explored whether people who read the messages, but do not actively contribute by posting themselves, (lurkers) profit to the same extent from use of online patient support groups as posters do.

The researchers noted, although little is known about lurkers in online patient support groups, some studies have been conducted on lurkers in other online communities. Opinions about lurking and lurkers vary considerably, with some poeple considering it negative bahaviour, using the resources of online groups without giving back to them, whilst others consider lurking to be acceptable or even beneficial, encouraging new members and discouraging an overload of posting. Lurking rates on various online groups are highly variable, but with an average of 45.5% of lurkers in health-related online support groups being reported. [1][2]

For the latest study, the researchers used Google to identify all Dutch online support groups for patients with breast cancer, Fibromyalgia Syndrome (Fibro), and arthritis. The owners of 19 groups then sent out invitations to complete an online survey, including questions demographic and health characteristics, use of and satisfaction with the online support group, empowering processes, and empowering outcomes. The online questionnaire was completed by 528 individuals, of which 109 (21%) identified themselves as lurkers. [1]

Lurkers were found to be slightly older than posters, with a shorter disease history and reported lower mental well-being. [1]

Posters were found to be visiting the online support groups significantly more often for social reasons, such as curiosity about how other members were doing, to enjoy themselves, as a part of their daily routine, and because other members expected them to be there. Lurkers and posters did not differ in their information-related reasons for visiting the online support group. [1]

Lurkers were significantly less satisfied with the online support group compared to posters. Although the researchers found that lurkers did not differ significantly from posters with regard to most empowering outcomes, such as “being better informed,” “feeling more confident in the relationship with their physician,” “improved acceptance of the disease,” “feeling more confident about the treatment,” “enhanced self-esteem,” and “increased optimism and control”, lurkers scored significantly lower for “enhanced social well-being”.

The researchers concluded that:

"[The] study revealed that participation in an online support group had the same profound effect on lurkers’ self-reported feelings of being empowered in several areas as it had on posters. Apparently, reading in itself is sufficient to profit from participation in an online patient support group."

However, actively contributing to an online support group could enhance lurker's social well-being.

References:

van Uden-Kraan CF, Drossaert CH, Taal E, Seydel ER, van de Laar MA. Self-reported differences in empowerment between lurkers and posters in online patient support groups. J Med Internet Res. 2008 Jun 30;10(2):e18.

Nonnecke B, Preece J. Lurker demographics: counting the silent. Proceedings of the SIGCHI Conference on Human Factors in Computing Systems April 1-6; The Hague, The Netherlands. New York: ACM Press 2000:73-80.

High Dose Amitriptyline not for Fibro

Thu, 14 Aug 2008 12:00:00 +0100

An article by Spanish researchers discussing amitriptyline as a treatment for Fibromyalgia Syndrome (Fibro) was this week e-published ahead of print in the journal Rheumatology. The researchers concluded that there was no evidence to support the use of amitriptyline for Fibro at higher doses or for longer than 8 weeks.

In order to assess the efficacy and safety of amitriptyline as a treatment for Fibro, a comprehensive computerized search in Medline (Pubmed), EMBASE and The Cochrane Library was carried out, looking for randomized controlled trials (RCTs) that compared amitriptyline vs placebo in adult patients suffering from Fibro. Ten study of moderate to high quality were identified, although the variability of the studies precluded a quantitative meta-analysis being carried out (i.e. the results could not simply be integrated).

Amitriptyline 25 mg/day (six RCTs) was found to be of benefit compared to placebo when considering pain, sleep, fatigue and overall patient and investigator impression. However, this benefit was generally seen at 6-8 weeks of treatment, with no benefit being noted at 12 weeks.

Amitriptyline 50 mg/day (four RCTs) did not demonstrate a benefit compared to placebo.

Neither dose of amitriptyline had an effect on the number of tender points the study participants were measured as having.

The researchers concluded that:

"A definitive clinical recommendation regarding the efficacy of amitriptyline for [Fibro] symptoms cannot be made. There is some evidence to support the short-term efficacy of amitriptyline 25 mg/day in FM. There is no evidence to support the efficacy of amitriptyline at higher doses or for periods [greater than] 8 weeks. "

The researchers went on to suggest that more stringent RCTs with follow-up periods are needed in order to determine the long-term efficacy and safety of amitriptyline and to define its role in the management of Fibro.

References:

Nishishinya B, Urrútia G, Walitt B, Rodriguez A, Bonfill X, Alegre C, Darko G. Amitriptyline in the treatment of fibromyalgia: a systematic review of its efficacy. Rheumatology (Oxford). 2008 Aug 12. [Epub ahead of print]

Waon Heat Therapy for Fibro

Thu, 21 Aug 2008 12:00:00 +0100

A recent article from Japanese researchers has shown that Waon Therapy, a specific kind of soothing warmth therapy, can be effective at helping to treat Fibromyalgia Syndrome (Fibro). [1]

For the Waon therapy, 13 female Fibro patients, spent 15 minutes relaxing in far infrared-ray dry sauna maintained at an even temperature of 60 degrees C, folowing which they were transferred to a room maintained at 26-27 degrees C where they were covered with a blanket from the neck down to keep them warm for 30 minutes. [1]

The pain Visual Analog Scale (VAS) and the Fibromyalgia Impact Questionnaire (FIQ) were used to assess subjective pain levels and symptom impact due to Fibro. After the first session of Waon therapy, all the patients experienced significant pain reduction of 11-70% and after 10 sessions of the therapy, the effects stabilised at 20-78% of pain reduction. Significant reductions in pain and symptoms were determined using the pain Visual Analog Scale (VAS) and the Fibromyalgia Impact Questionnaire (FIQ), and these reductions in pain and symptoms were seen throughout the observation period. [1]

The researchers concluded that:

"Waon therapy is effective for the treatment of Fibromyalgia Syndrome." [1]

Heat therapies of various forms are often used by Fibro patients, with heated pool treatment being included in the EULAR evidence-based recommendations for the management of Fibromyalgia Syndrome. [2] Heat was also rated as one of the most effective management modalities by an internet survey of 2,596 people with Fibro that was carried out last year. [3]

References:

Matsushita K, Masuda A, Tei C. Efficacy of Waon therapy for fibromyalgia. Intern Med. 2008;47(16):1473-6. Epub 2008 Aug 15.
Reference: 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; EULAR. EULAR evidence-based recommendations for the management of fibromyalgia syndrome. Ann Rheum Dis. 2008 Apr;67(4):536-41. Epub 2007 Jul 20.
Bennett RM, Jones J, Turk DC, Russell IJ, Matallana L. An internet survey of 2,596 people with fibromyalgia. BMC Musculoskelet Disord. 2007 Mar 9;8:27

Statins and muscle pain

Mon, 25 Aug 2008 12:00:00 +0100

A recently e-published article from a team of researchers at a Harvard teaching hospital has suggested that statin users are more likely to have musculoskeletal pain. [1]

Statins (3-hydroxy-3-methylglutaryl coenzyme A or HMG-CoA inhibitors) are a class of medications that are used to lower cholesterol levels in people with or at risk of cardiovascular disease. They work by inhibiting an HMG-CoA enzyme, stimulating LDL receptors, resulting in more low-density lipoprotein (LDL - often known as "bad cholesterol") being taken from the bloodstream and a decrease in blood cholesterol levels.

Muscle effects are the most commonly reported side effects of statins, with muscle cramps, myalgia (muscle pain), myopathy (muscle problems with the primary symptom of muscle weakness due to dysfunction of the muscle fibers), rhabdomyolysis (the breakdown of muscle fibers) and arthralgias (joint pains) being reported. Non-urgent myalgias are relatively common, with rhabdomyolysis being rare.

However, in placebo-controlled trials the incidence of muscle pain is often similar for placebo and active control groups.

This study sought to evaluate whether statin use was associated with a higher prevalence of musculoskeletal pain in a nationally (USA) representative sample. [1]

Data from the US National Health and Nutrition Examination Survey (NHANES) 1999-2002 was used. This gave 3,580 adult "participants", 40 years of age or over, without arthritis, who were interviewed at home and examined in a mobile examination center. They were asked about sociodemographic characteristics, health conditions, medication use, and musculoskeletal pain. Height, weight, blood pressure, ankle brachial index, and cholesterol were measured. The ankle brachial index is a measure of the reduction in blood pressure between arteries in the upper arms and the ankles, and as such, it is used to detect evidence of blockages in the circulatory system. [1]

The study analysed the data to determine the prevalence and adjusted odds ratios of any musculoskeletal pain and musculoskeletal pain in 4 different anatomical regions (neck/upper back, upper extremities, lower back, and lower extremities) by statin use during the last 30 days. [1]

There were 402 statin users in the data used and the study found that 22% of these reported musculoskeletal pain in at least 1 anatomical region during the 30 days previous to the data being collected, compared to 16.7% of those who did not use a statin. Compared to persons who did not use statins, those who used statins had multivariable-adjusted odds ratios of 1.50 for any musculoskeletal pain, 1.59 for lower back pain, and 1.50 for lower extremity pain. [1]

The researchers concluded that musculoskeletal pain is common in adults 40 years of age or over, without arthritis, and that:

"In this nationally representative sample, statin users were significantly more likely to report musculoskeletal pain."

One of the researchers from the team that carried out this study has also co-authored another paper that was published this month in the journal Pharmacogenomics. In this it is suggested that a gene required for muscle atrophy is implicated in the pathophysiology of statin-induced muscle injury, such as rhabdomyolysis. [3]

Statin use may be problematic for Fibromyalgia Syndrome patients because of the risk of increased pain. [4] However, an article published earlier this year suggests that the risk of myalgia and other potentially treatment-limiting muscle effects can be reduced through: proper monitoring; statin dosage reduction, discontinuation, and rechallenge; and the use of treatment alternatives, such as statins which are less likely to cause side effects. Statins can thus be used for their cardiovascular benefits whilst minimising the risk of muscle effects. [5]

References:

Buettner C, Davis RB, Leveille SG, Mittleman MA, Mukamal KJ. Prevalence of musculoskeletal pain and statin use. J Gen Intern Med. 2008 Aug;23(8):1182-6. Epub 2008 May 1.
Silva MA, Swanson AC, Gandhi PJ, Tataronis GR. Statin-related adverse events: a meta-analysis. Clin Ther. 2006 Jan;28(1):26-35.
Buettner C, Lecker SH. Molecular basis for statin-induced muscle toxicity: implications and possibilities. Pharmacogenomics. 2008 Aug;9(8):1133-42.
Mascitelli L, Pezzetta F, Goldstein MR. Detrimental effect of statin therapy in women with fibromyalgia. Arch Intern Med. 2008 Jun 9;168(11):1228-9.
Jacobson TA. Toward "pain-free" statin prescribing: clinical algorithm for diagnosis and management of myalgia. Mayo Clin Proc. 2008 Jun;83(6):687-700.

Pain Related Cognitive Behavioral Mechanisms and Fibro

Wed, 27 Aug 2008 12:00:00 +0100

An article by Dutch researchers has suggested that screening for pain persistance and pain avoidance patterns in patients with Fibromyalgia Syndrome (Fibro) can lead to finding more effective treatments for individual patients. [1]

In the article, published in the International Journal of Behavioural Medicine, the researchers say that the variations between Fibro patients as regards pain-related cognitive-behavioral mechanisms, has been proposed as a reason why some patients do better than others with some treatments. [1]

Pain-related cognitive-behavioral mechanisms include pain avoidance, characterised by avoiding activities because they may cause pain (even though, in some cases, e.g. with exercise, this can lead to more pain in the long-term), and pain persistance, characterised by continuing with activities in spite of pain (even though this may lead to more pain).

The Dutch researchers used a self-reported screening instrument, that assesses pain-avoidance behavior, to distinguish betweenpatients with pain-persistence and pain-avoidance patterns. [1]

The two resultant groups of patients were then compared with regard to several pain-related cognitive-behavioral factors, as well as their performance on a physical fitness test. They were also compared with regard to the judgments of trained therapists based on a semi-structured interview. [1]

They found that the results of the self-reported screening instrument they used corresponded with the other results in terms of which patients were assessed as having pain-avoidance and pain-persistence patterns.

The researchers concluded that:

"...a short self-report screening instrument can be used to distinguish between pain-avoidance and pain-persistence patterns within the heterogeneous population of [Fibro] patients, which offers promising possibilities to improve treatment efficacy by tailoring treatment to specific patient patterns." [1]

A previous article published earlier this year discussed 2 case studies where cognitive behavioural therapy (CBT) and exercise therapy for patients with Fibro were tailored for whether the patients fell into pain-avoidance or pain-persistence pattern groups. [2]

That study found that tailoring the CBT and exercise therapy to take the pain-avoidance/pain-persistence patterns into account can contribute to the improvement of the care of Fibro patients. [2]

References:

van Koulil S, Kraaimaat FW, van Lankveld W, van Helmond T, Vedder A, van Hoorn H, Cats H, van Riel PL, Evers AW. Screening for pain-persistence and pain-avoidance patterns in fibromyalgia. Int J Behav Med. 2008;15(3):211-20.
van Koulil S, van Lankveld W, Kraaimaat FW, van Helmond T, Vedder A, van Hoorn H, Cats H, van Riel PL, Evers AW. Tailored cognitive-behavioral therapy for fibromyalgia: two case studies. Patient Educ Couns. 2008 May;71(2):308-14. Epub 2008 Jan 9.

Juvenile Fibro and Anxiety

Wed, 27 Aug 2008 12:00:00 +0100

A recent article has suggested that children with Fibromyalgia Syndrome (Fibro) are more likely to suffer from anxiety disorders, and that anxiety is linked to poorer functioning in these patients. [1]

The article, from a group of researchers in the Division of Behavioral Medicine and Clinical Psychology at the University of Cincinnati College of Medicine, Ohio, USA, was published in the September issue of The Clinical Journal of Pain.

Their study aimed to assess the prevalence of mood, anxiety, and behavioral disorders in children and adolescents with juvenile primary fibromyalgia syndrome (JPFS) and to assess the relationship between psychiatric disorders and the severity of their Fibro. [1]

The study looked at 76 children and adolescents diagnosed with JPFS (ages 11 to 18 years) in pediatric rheumatology clinics at 4 hospitals in the Midwest area of the USA. Standardized psychiatric interviews were conducted with the children/adolescents and their parents or primary caregivers, and measures of symptom severity, including pain intensity and physician global ratings, were obtained for the patients. [1]

The researchers found that 67.1% of the patients had at least 1 current psychiatric diagnosis and 71.5% had at least 1 lifetime psychiatric diagnosis, with the DSM-IV (Diagnostic and Statistical Manual of Mental Disorders-fourth edition) being used to define psychiatric diagnoses. [1]

The most frequent psychiatric diagnosis was anxiety disorder (57.5% of patients). [1]

Although mood difficulties were also common, the researchers found that the presence of major depression in the young participants was lower than has been reported for adults with Fibro. [1]

Physicians' global assessment of functioning was significantly lower for patients with a current anxiety disorder. However, it was found that there were no significant differences in pain severity among patients with and without anxiety, mood, or behavioral disorders. [1]

The researchers concluded that:

"There seems to be a high prevalence of anxiety disorders in patients with JPFS, and presence of anxiety disorder is associated with poorer physician-rated functioning. Future research should explore whether early anxiety symptoms are predictive of long-term functioning."

According to an article published in an Icelandic journal earlier this year, the estimated prevalence of juvenile primary fibromyalgia syndrome (JPFS) is 1.2%-6.2%, with prevalence being higher in girls than in boys, and peaking at the time of puberty. The development of JPFS is related to many factors, such as genetic and anatomic factors, disordered sleep and psychological distress. [2]

The diagnosis of JPFS is based on the criteria defined by Yunus and Masi in 1985, which include generalised musculoskeletal aching at three or more regions for at least three months and at least five of eighteen typical tender points. [2][3]

Although there is an emerging understanding of JPFS and its treatment, [2] the situation in the UK hasn't improved much since 1985, when Masi and Yunus (the now legendary Fibro expert, Dr. Muhammad B. Yunus), wrote that:

"Juvenile PFS is often misdiagnosed. Recognition of this common rheumatologic condition in juveniles is important in order to avoid unwarranted investigations and improper management."

References:

Kashikar-Zuck S, Parkins IS, Graham TB, Lynch AM, Passo M, Johnston M, Schikler KN, Hashkes PJ, Banez G, Richards MM. Anxiety, mood, and behavioral disorders among pediatric patients with juvenile fibromyalgia syndrome. Clin J Pain. 2008 Sep;24(7):620-6.
Baldursdóttir S. [Juvenile primary fibromyalgia syndrome--review] Laeknabladid. 2008 Jun;94(6):463-72.
Yunus MB, Masi AT. Juvenile primary fibromyalgia syndrome. A clinical study of thirty-three patients and matched normal controls. Arthritis Rheum. 1985 Feb;28(2):138-45.

Hydrotherapy for Fibromyalgia Syndrome

Sun, 31 Aug 2008 12:00:00 +0100

Hydrotherapy is useful in managing Fibromyalgia Syndrome (Fibro), according to a recently e-published study from researchers at the Health and Rehabilitation Sciences Research Institute at the University of Ulster. [1]

The researchers carried out a systematic review of the published results of previous trials to examine the effectiveness of hydrotherapy in the management of Fibro. [1] A number of databases of scientific articles (AMED, BNI, CINAHL, The Cochrane Library, EMBASE, MEDLINE, ProQuest, PubMed, Science Direct and Web of Science) were searched for articles published between 1990 and July 2006 that contained the keywords: 'fibromyalgia' and 'hydrotherapy', 'balneotherapy', 'aqua therapy', 'pool therapy', 'water therapy', 'swimming', 'hydrogalvanic', 'spa therapy', 'physiotherapy', 'physical therapy' and 'rehabilitation'. [1]

The randomised controlled trials (RCTs) found in the search were then assessed for methodological quality using the van Tulder scale and 10 RCTs were found that met the inclusion criteria. [1]

These 10 RCTS showed that the use of hydrotherapy as a treatment for Fibro caused positive outcomes to be reported for pain, health-status and tender point count. [1]

The researchers concluded that:

"There is strong evidence for the use of hydrotherapy in the management of [Fibromyalgia Syndrome]". [1]

The EULAR evidence based recommendations for the management of Fibromyalgia Syndrome recommend that

"Heated pool treatment, with or without exercise, is effective." [2]

References:

McVeigh JG, McGaughey H, Hall M, Kane P. The effectiveness of hydrotherapy in the management of fibromyalgia syndrome: a systematic review. Rheumatol Int. 2008 Aug 27. [Epub ahead of print]
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; EULAR. EULAR evidence-based recommendations for the management of fibromyalgia syndrome. Ann Rheum Dis. 2008 Apr;67(4):536-41. Epub 2007 Jul 20.

Physical functioning limitations with Fibromyalgia Syndrome

Sun, 31 Aug 2008 12:00:00 +0100

Women with Fibro may have more physical functional limitations than the average 80-year old woman, according to a survey carried out by the American National Fibromyalgia Association (NFA). [1]

For an article recently e-published ahead of print in the journal Womens Health Issues, researchers including NFA founder and president, Lynne Matallana, carried out a secondary analysis using data from an Internet-based survey posted on the National Fibromyalgia Association website. [1]

The data used included 1,735 women aged 31-78 years who reported being diagnosed with Fibromyalgia Syndrome (Fibro). [1]

More than 25% of the women reported having difficulty taking care of personal needs and bathing. [1]

More than 60% reported difficulty doing light household tasks, going up/down 1 flight of stairs, walking half a mile, and lifting or carrying 10 lbs. [1]

More than 90% of the women reported having difficulty doing heavy household tasks, lifting or carrying 25 lbs, and doing strenuous activities. [1]

The researchers also found that women with lower functional ability reported higher levels of fatigue, pain, spasticity, depression, restless legs, balance problems, dizziness, fear of falling, and bladder problems. [1]

They concluded that:

"The average woman in this sample reported having less functional ability related to activities of daily living and instrumental activities of daily living than the average community-dwelling woman in her 80s." [1]

They also noted that several symptoms and secondary conditions were found to be associated with limited functioning. Targeting these symptoms/conditions specifically may be important in terms of future interventions. [1]

References:

Jones J, Rutledge DN, Jones KD, Matallana L, Rooks DS. Self-Assessed Physical Function Levels Of Women With Fibromyalgia A National Survey. Womens Health Issues. 2008 Aug 22. [Epub ahead of print]

Specialist Nurses can diagnose Fibromyalgia Syndrome

Sun, 07 Sep 2008 12:00:00 +0100

A recent article has suggested that the use of specialised nurses in the diagnostic process of Fibromyalgia Syndrome (Fibro) is a trustworthy, successful and cost-effective approach that saves waiting time and provides greater patient satisfaction. [1]

The article, e-published ahead of print in the journal Arthritis and Rheumatism discussed a study that aimed to evaluate the substitution of specialised rheumatology nurses for rheumatologists in diagnosing Fibro. [1]

One hundred and ninety-three patients with Fibro like symptoms, who were referred for diagnosis, were randomly allocated to either a study group to be diagnosed by a specialised rheumatology nurse (SRN group) or to a control group to be diagnosed by a rheumatologist (RMT group). [1]

The patients allocated to the specialised rheumatology nurse group were seen within 3 weeks by a nurse who took a structured patient history and initiated routine laboratory tests. During a 5-minute supervision session, the rheumatologist was informed by the nurse about medical history, performed a brief physical examination, and confirmed or rejected the nurse's diagnosis. [1]

The patients allocated to the rheumatologist group were seen by a rheumatologist after a regular waiting period of 3 months. [1

The outcome measures used were an initial agreement between the nurse and rheumatologist in the group of patients allocated to the specialised rheumatology nurse group, final diagnosis after 12-24 months of follow-up, patient satisfaction, and diagnostic costs. [1]

The study found that the average waiting times were 2.8 weeks for the patients allocated to the specialised rheumatology nurse group and 12.1 weeks for the patients allocated to the rheumatologist group. Eight of the patients allocated to the rheumatologist group cancelled their appointments because of the waiting time. [1]

There was excellent agreement between the diagnoses made by the rheumatologist and the diagnoses made by the specialised rheumatologist nurse. After 12-24 months of followup, none of the initial diagnoses were recalled in either group. [1]

The patients allocated to the specialised rheumatology nurse group were significantly more satisfied and average diagnostic were lower for this group (219 Euros vs 281 Euros) compared to the patients allocated to the rheumatologist group . [1]

The researchers concluded that:

"Substituting specialized nurses for rheumatologists in the diagnostic process of [Fibro] is a trustworthy and successful approach that saves waiting time, provides greater patient satisfaction, and is cost-effective."

Specialist nurses are used for a number of conditions, including neurological conditions such as Multiple Sclerosis. In general, they are found to decrease costs and increase patient satisfaction.

References:

Kroese ME, Schulpen GJ, Bessems MC, Severens JL, Nijhuis FJ, Geusens PP, Landewé RB. Substitution of specialized rheumatology nurses for rheumatologists in the diagnostic process of fibromyalgia: A randomized controlled trial. Arthritis Rheum. 2008 Aug 29;59(9):1299-1305. [Epub ahead of print]

Fibromyalgia Syndrome has greater impact on patients

Sun, 07 Sep 2008 12:00:00 +0100

Three articles that were first published in late 2007 concluded that Fibromyalgia Syndrome (Fibro) has more of an impact on patients' lives and has more consequences for patients than many other chronic conditions and forms of widespread pain. [1] [2] [3]

The first article, on a study by reseachers Cöster et al at Linköping University, Sweden, was published in the European Journal of Pain. The study found that Fibro was associated with more severe symptoms/consequences for daily life and higher pain severity than chronic widespread pain without widespread allodynia. [1]

Allodynia is “Pain from stimuli which are not normally painful”, such as pain from a stroking motion on the skin.

The researchers said that Fibro is currently classified as chronic widespread pain with widespread allodynia to pressure pain, and that there have been few studies comparing Fibro with chronic widespread pain that does not have associated widespread allodynia. [1]

The study used a randomly selected sample from the general population, with a postal questionnaire and pain mannequin being sent to 9952 people. The response rate was 76.7% and the pain drawings showed that 345 people had widespread pain (in all four extremities and axially). Clinical examination, including a manual tender point examination, was performed in 125 subjects and these people answered commonly used questionnaires on pain, quality of life, coping strategies, depression, and anxiety. [1]

Chronic widespread pain without widespread allodynia to pressure pain was found in 4.5% in the population and Fibro was found in 2.5% of the population. [1]

The study found that, compared with chronic widespread pain without widespread allodynia, Fibro was associated with more severe symptoms/consequences for daily life and higher pain severity. Similar coping strategies were found in both groups. [1]

The second article, describing a study by Hoffman and Dukes in Connecticut, USA, was published in the International journal of clinical practice. [2]

They carried out a review of 37 studies of Fibro that measured health status with the 36-item Medical Outcomes Study Short-Form Health Survey (SF-36) or the 12-item Short-Form Health Survey (SF-12), describing how the health status profile of people with Fibro compares to that of people in the general population and patients with other health conditions. [2]

Hoffman and Dukes found that studies performed worldwide showed that people with Fibro were significantly more impaired than people in the general population in terms of all of the eight health factors assessed. [2]

These factors include:

Physical functioning
Role functioning difficulties caused by physical problems
Bodily pain
General health
Vitality (energy vs. fatigue)
Social functioning
Role functioning difficulties caused by emotional problems and mental health.

Groups of Fibro patients in the studies reviewed had both mental health and physical health scores below the general population and poorer overall health status compared to those with other specific pain conditions. Fibro patients had similar or significantly lower (poorer) physical and mental health status scores compared to those with rheumatoid arthritis, osteoarthritis, osteoporosis, systemic lupus erythematosus, myofacial pain syndrome, primary Sjögren’s syndrome and others. [2]

Hoffman and Dukes concluded that people with Fibro had an overall health status burden greater than that of people with other specific pain conditions that are widely accepted as impairing. [2]

The third article, from researchers Perruccio et al at the Toronto Western Research Institute, was published in the Journal of epidemiology and community health. [3]

Their study examined the relative impact of 13 chronic conditions using 3 outcome measures:

Activity limitations
Self-rated health
Physician visits

They found that, at the individual level, Fibro or Chronic Fatigue Syndrome and cancer (and to a lesser extent stroke and heart disease) were associated with an increased risk of both activity limitations and a self-rated health status of fair or poor (as opposed to good). [3]

These studies may be useful in demonstrating that Fibro can have a significant effect on a Fibro patient's life.

References:

Cöster L, Kendall S, Gerdle B, Henriksson C, Henriksson KG, Bengtsson A. Chronic widespread musculoskeletal pain - a comparison of those who meet criteria for fibromyalgia and those who do not. Eur J Pain. 2008 Jul;12(5):600-10. Epub 2007 Nov 19.
Hoffman DL, Dukes EM. The health status burden of people with fibromyalgia: a review of studies that assessed health status with the SF-36 or the SF-12. Int J Clin Pract. 2008 Jan;62(1):115-26. Epub 2007 Nov 24.
Perruccio AV, Power JD, Badley EM. The relative impact of 13 chronic conditions across three different outcomes. J Epidemiol Community Health. 2007 Dec;61(12):1056-61.