Increased Levels of Neurotrophins Are Not Specific for Chronic Migraine: Evidence from Primary Fibromyalgia Syndrome.

Sarchielli P, Mancini ML, Floridi A, Coppola F, Rossi C, Nardi K, Acciarresi M, Alberto Pini L, Calabresi P.

Neurologic Clinic, Department of Medical and Surgical Specialties and Public Health, University of Perugia, Perugia, Italy.

All data obtained in experimental animal pain models support the role of nerve growth factor (NGF) as a putative candidate intervening in the pathogenesis of chronic pain, including chronic daily headache (CDH). Few studies have been carried out to establish its role in maintaining pain states in humans. The present study was aimed at investigating cerebrospinal fluid (CSF) levels of NGF and brain-derived neurotrophic factor (BDNF), both measured by sensitive immunoassay, in 20 chronic migraine (CM) patients and 20 patients affected by primary fibromyalgia syndrome (PFMS), compared with those of 20 age-matched control subjects. Significantly higher levels of both neurotrophins and glutamate were found. A significantly positive correlation emerged between CSF values of BDNF and those of NGF (See Note) in CM and PFMS patients, respectively. These findings suggest the possibility of a NGF-mediated up-regulation of BDNF involved in the pathophysiological events underlying long-term neuroplastic changes in persistent chronic painful conditions, such as CM and fibromyalgia. NGF might indirectly exert its effect through enhancing glutamatergic transmission via BDNF. The above mechanisms could account for sustained central sensitization in both chronic pain states. PERSPECTIVE: This article presents findings of higher NGF and BDNF levels correlated to increased glutamate levels in the CSF of both chronic migraine and fibromyalgia patients. This opens new insights into the pathogenic mechanisms of chronic pain and offers clinicians new therapeutic perspectives targeting the above mechanisms in both painful disorders.

PMID: 17611164 [PubMed - as supplied by publisher]

1: J Pain. 2007 Jul 3; [Epub ahead of print]

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Note: (r = .61, P

Fibromyalgia patients show an abnormal dopamine response to pain.

Wood PB, Schweinhardt P, Jaeger E, Dagher A, Hakyemez H, Rabiner EA, Bushnell MC, Chizh BA.

McGill University Centre for Research on Pain, Faculty of Dentistry, 3640 University Street, Strathcona Building, Montreal, QC, Canada, H3A 2B2.

Fibromyalgia is characterized by chronic widespread pain and bodily tenderness and is often accompanied by affective disturbances. Accumulating evidence indicates that fibromyalgia may involve a dysfunction of modulatory systems in the brain. While brain dopamine is best known for its role in pleasure, motivation and motor control, recent evidence suggests that it is also involved in pain modulation. Because dopamine is implicated in both pain modulation and affective processing, we hypothesized that fibromyalgia may involve a disturbance of dopaminergic neurotransmission. Fibromyalgia patients and matched healthy control subjects were subjected to deep muscle pain produced by injection of hypertonic saline into the anterior tibialis muscle. In order to determine the endogenous release of dopamine in response to painful stimulation, we used positron emission tomography to examine binding of [(11)C]-raclopride (D2/D3 ligand) in the brain during injection of painful hypertonic saline and nonpainful normal saline. Fibromyalgia patients experienced the hypertonic saline as more painful than healthy control subjects. Control subjects released dopamine in the basal ganglia during the painful stimulation, whereas fibromyalgia patients did not. In control subjects, the amount of dopamine release correlated with the amount of perceived pain but in fibromyalgia patients no such correlation was observed. These findings provide the first direct evidence that fibromyalgia patients have an abnormal dopamine response to pain. The disrupted dopaminergic reactivity in fibromyalgia patients could be a critical factor underlying the widespread pain and discomfort in fibromyalgia and suggests that the therapeutic effects of dopaminergic treatments for this intractable disorder should be explored.

PMID: 17610577 [PubMed - in process]

1: Eur J Neurosci. 2007 Jun;25(12):3576-82.

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Cranial electrotherapy stimulation and fibromyalgia.

Gilula MF.

President and Director,
Life Energies Research Institute,
2510 Inagua Avenue, Miami,
FL 33133, USA.
mgilula@mindspring.com.

Cranial electrotherapy stimulation (CES) is a well-documented neuroelectrical modality that has been proven effective in some good studies of fibromyalgia (FM) patients. CES is no panacea but, for some FM patients, the modality can be valuable. This article discusses aspects of both CES and FM and how they relate to the individual with the condition. FM frequently has many comorbidities such as anxiety, depression, insomnia and a great variety of different rheumatologic and neurological symptoms that often resemble multiple sclerosis, dysautonomias, chronic fatigue syndrome and others. However, despite long-standing criteria from the American College of Rheumatology for FM, some physicians believe there is probably no single homogeneous condition that can be labeled as FM. Whether it is a disease, a syndrome or something else, sufferers feel like they are living one disaster after another. Active self-involvement in care usually enhances the therapeutic results of various treatments and also improves the patient’s sense of being in control of the condition. D-ribose supplementation may prove to significantly enhance energy, sleep, mental clarity, pain control and well-being in FM patients. A form of evoked potential biofeedback, the EPFX, is a powerful stress reduction technique which assesses the chief stressors and risk factors for illness that can impede the FM patient’s built-in healing abilities. Future healthcare will likely expand the diagnostic criteria of FM and/or illuminate a group of related conditions and the ways in which the conditions relate to each other. Future medicine for FM and related conditions may increasingly involve multimodality treatment that features CES as one significant part of the therapeutic regimen. Future medicine may also include CES as an invaluable, cost-effective add-on to many facets of clinical pharmacology and medical therapeutics.

PMID: 17605684 [PubMed - in process]

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Cognitive functioning and aging in women.

Badgio PC, Worden BL.

pbadgio@msn.com

Deficits in cognitive function may impact one’s ability to attend to stimuli, think clearly, reason, and remember. Impaired cognitive function is a common complaint among older women presenting for treatment in both mental health and medical care settings, and differential diagnosis of type and extent of cognitive impairment is important for appropriate treatment planning and prognosis. Although overall gender differences in prevalence of cognitive dysfunction are minimal, it is important when treating older women to take into account unique challenges they face in the aging process that impact the cause, type and extent of cognitive complaints with which they present in clinical settings. The current paper provides an overview to guide accurate diagnosis, particularly in women, of different types of cognitive impairment under the broad category of dementias, including Alzheimer’s, Lewy Body Disease, Vascular Dementia, and due to general medical conditions such as coronary artery bypass surgery, head injury, menopause, hypothyroidism, breast cancer treatment, Fibromyalgia, and chronic fatigue. In addition, emotional factors such as depression in older female patients complicate differential diagnosis of cognitive impairment and must be addressed. Given the multiplicity of causes of cognitive difficulties for women across the life span, careful assessment is crucial; the current paper reviews assessment strategies to prepare an integrated, biopsychosocial strategy for identifying particular cognitive deficits and related psychological and medical problems. In addition, prognostic indicators and treatment planning are discussed to help the practitioner organize an empathic, reasoned and multifaceted treatment approach to maximize recovery, minimize deterioration, and manage symptoms for older women in the context of their social support system and living environment.

PMID: 17588877 [PubMed - in process]

1: J Women Aging. 2007;19(1-2):13-30.Links

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Further legitimization of fibromyalgia as a true medical condition

Contact: Ethel Cathers
e.cathers@elsevier.com
215-239-3523
Elsevier Health Sciences

Philadelphia, June 25, 2007 — Fibromyalgia, a chronic, widespread pain in muscles and soft tissues accompanied by fatigue, is a fairly common condition that does not manifest any structural damage in an organ. Twenty-five years ago, Muhammad B. Yunus, MD, and colleagues published the first controlled study of the clinical characteristics of fibromyalgia syndrome. That seminal article, published in Seminars in Arthritis and Rheumatism, led directly to formal recognition of this disease by the medical community. In the June 2007 issue of Seminars in Arthritis and Rheumatism, Dr. Yunus once again makes an enormous contribution to the field of chronic pain and fatigue by meticulously synthesizing and interpreting the extensive body of scientific literature on fibromyalgia and his own insights into the concept of central sensitivity syndromes (CSS).

Fibromyalgia, affecting approximately 2% of the US population, is an example of a class of maladies called CSS. These diseases are based on neurochemical abnormalities and include irritable bowel syndrome, migraine and restless legs syndrome.

Incorporating a critical review of over 225 publications and the author’s broad experience in fibromyalgia and related diseases, Dr. Yunus describes 13 separate conditions that are related to central sensitization (CS), where the central nervous system (spinal cord and brain) becomes extremely sensitized on certain parts of the body, so that even mild pressure or touch would cause much pain. Such hypersensitivity may also be associated with other symptoms such as poor sleep and fatigue.

According to Dr. Yunus, “CSS are the most common diseases that are based on real neurochemical pathology and cause real pain and suffering. In some patients stress and depression may contribute to the symptoms but they are all based on objective changes in the central nervous system.”

Dr. Norman L. Gottlieb, Editor of Seminars in Arthritis and Rheumatism, believes that this article “advances our understanding of fibromyalgia, unifies and advances concepts, and suggests that this and several other common disorders have much in common in terms of their biopsychosocial development. This, hopefully, will expand both clinical and research interest in this group of diseases and lead to advances in therapy for many of them.”

In an accompanying editorial John B. Winfield, MD, comments, “Without question, Muhammad Yunus is the father of our modern view of fibromyalgia…. Yunus, who took a rather more biological approach to fibromyalgia in the past, now emphasizes a biopsychosocial perspective. In my view, this is tremendously important because it is the only way to synthesize the disparate contributions of such variables as genes and adverse childhood experiences, life stress and distress, posttraumatic stress disorder, mood disorders, self-efficacy for pain control, catastrophizing, coping style, and social support into the evolving picture of central nervous system dysfunction vis-a-vis chronic pain and fatigue ….Science and medicine now have a rational scaffolding for understanding and treating chronic pain syndromes previously considered to be ‘functional’ or ‘unexplained.’ …Neuroscience research will continue to reveal the mechanisms of CS, but only if informed through a biopsychosocial perspective and with the interdisciplinary collaboration of basic scientists, psychologists, sociologists, epidemiologists, and clinicians.”

Dr. Yunus concludes that CSS is an important new concept that embraces the biopsychosocial model of disease. He advocates further critical studies to fully test this concept which seems to have important significance for new directions for research and patient care involving physician and patient education. “Each patient, irrespective of diagnosis,” says Dr. Yunus, “should be treated as an individual, considering both the biological and psychosocial contributions to his or her symptoms and suffering.”

###
The article is “Fibromyalgia and Overlapping Disorders: The Unifying Concept of Central Sensitivity Syndromes” by Muhammad B. Yunus, MD, Professor of Medicine, Section of Rheumatology, The University of Illinois College of Medicine at Peoria, Peoria, Illinois. The accompanying editorial is “Fibromyalgia and Related Central Sensitivity Syndromes: Twenty-Five Years of Progress” by John B. Winfield, MD, University of North Carolina School of Medicine. Both appear in the June issue of Seminars in Arthritis and Rheumatism, Vol. 36:6, published by Elsevier.

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Effectiveness of Massage Therapy for Chronic, Non-malignant Pain: A Review.

1: Evid Based Complement Alternat Med. 2007 Jun;4(2):165-79. Epub 2007 Feb 5.

Tsao JC.

Pediatric Pain Program, Department of Pediatrics, David Geffen School of Medicine at UCLA, USA.

Previous reviews of massage therapy for chronic, non-malignant pain have focused on discrete pain conditions. This article aims to provide a broad overview of the literature on the effectiveness of massage for a variety of chronic, non-malignant pain complaints to identify gaps in the research and to inform future clinical trials. Computerized databases were searched for relevant studies including prior reviews and primary trials of massage therapy for chronic, non-malignant pain. Existing research provides fairly robust support for the analgesic effects of massage for non-specific low back pain, but only moderate support for such effects on shoulder pain and headache pain. There is only modest, preliminary support for massage in the treatment of fibromyalgia, mixed chronic pain conditions, neck pain and carpal tunnel syndrome. Thus, research to date provides varying levels of evidence for the benefits of massage therapy for different chronic pain conditions. Future studies should employ rigorous study designs and include follow-up assessments for additional quantification of the longer-term effects of massage on chronic pain.

PMID: 17549233 [PubMed - in process]

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Gabapentin Shown Effective for Fibromyalgia Pain

FOR IMMEDIATE RELEASE
Monday, June 11, 2007

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Ray Fleming
301-496-8190

New research supported by the National Institutes of Health’s National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) shows that the anticonvulsant medication gabapentin, which is used for certain types of seizures, can be an effective treatment for the pain and other symptoms associated with the common, often hard-to-treat chronic pain disorder, fibromyalgia.

In the NIAMS-sponsored, randomized, double-blind clinical trial of 150 women (90 percent) and men with the condition, Lesley M. Arnold, M.D., director of the Women’s Health Research Program at the University of Cincinnati College of Medicine, and her colleagues found that those taking gabapentin at dosages of 1,200 to 2,400 mg daily for 12 weeks displayed significantly less pain than those taking placebo. Patients taking gabapentin also reported significantly better sleep and less fatigue. For the majority of participants, the drug was well tolerated. The most common side effects included dizziness and sedation, which were mild to moderate in severity in most cases.

NIAMS Director Stephen I. Katz. M.D., Ph.D., remarked that “While gabapentin does not have Food and Drug Administration approval for fibromyalgia, I believe this study offers additional insight to physicians considering the drug for their fibromyalgia patients. Fibromyalgia is a debilitating condition for which current treatments are only modestly effective, so a study such as this is potentially good news for people with this common, painful condition.”

Fibromyalgia is a chronic disorder characterized by chronic, widespread muscle pain and tenderness, and is frequently accompanied by fatigue, insomnia, depression, and anxiety. It affects three million to six million Americans, mostly women, and can be disabling.

The precise cause of fibromyalgia in not known, but research suggests it is related to a problem with the central nervous system’s processing of pain. As with some other chronic pain conditions, people with fibromyalgia often develop a heightened response to stimuli, experiencing pain that would not cause problems in other people. Yet, unlike many other pain syndromes, there is no physical evidence of inflammation or central nervous system damage.

Although gabapentin has little, if any, effect on acute pain, it has shown a robust effect on pain caused by a heightened response to stimuli related to inflammation or nerve injury in animal models of chronic pain syndromes. Researchers have suspected that it might have the same effect in people with fibromyalgia. The new research, published in the April 2007 edition of Arthritis & Rheumatism, indicates the suspicions were correct.

Although the researchers cannot say with certainty how gabapentin helps reduce pain, Dr. Arnold says one possible explanation involves the binding of gabapentin to a specific subunit of voltage-gated calcium channels on neurons. “This binding reduces calcium flow into the nerve cell, which reduces the release of some signaling molecules involved in pain processing,” she says.

How gabapentin improves sleep and other symptoms is less clear, and there are probably different mechanisms involved in fibromyalgia symptoms. “Gabapentin improved sleep, which is an added benefit to patients with fibromyalgia who often report unrefreshing or disrupted sleep,” Dr. Arnold says.

What is important is that people with fibromyalgia now have a potential new treatment option for a condition with few effective treatments. “Studies like this give clinicians evidence-based information to guide their treatment of patients,” says Dr. Arnold.

The mission of the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), a part of the Department of Health and Human Services’ National Institutes of Health, is to support research into the causes, treatment and prevention of arthritis and musculoskeletal and skin diseases; the training of basic and clinical scientists to carry out this research; and the dissemination of information on research progress in these diseases. For more information about NIAMS, call the information clearinghouse at (301) 495-4484 or (877) 22-NIAMS (free call) or visit the NIAMS website at http://www.niams.nih.gov.

The National Institutes of Health (NIH) — The Nation’s Medical Research Agency — includes 27 Institutes and Centers and is a component of the U.S. Department of Health and Human Services. It is the primary federal agency for conducting and supporting basic, clinical and translational medical research, and it investigates the causes, treatments, and cures for both common and rare diseases. For more information about NIH and its programs, visit http://www.nih.gov.

Arnold, LM et al. Gabapentin in the treatment of fibromyalgia; a randomized, double-blind, placebo-controlled multicenter trial. Arthritis Rheum. 2007; 56: 1336-1344.

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A closer look at pain and hepatitis C: Preliminary data from a veteran population.

1: J Rehabil Res Dev. 2007;44(2):231-44.

Silberbogen AK, Janke EA, Hebenstreit C.

VA Boston Healthcare System, Psychology Service (116B), 150 South Huntington Avenue, Boston, MA 02130. amy.silberbogen@va.gov.

An association between the hepatitis C virus (HCV) and various pain diagnoses, including arthritis, fibromyalgia, and peripheral neuropathy, has been reported. In this article, we review the literature on the relationship between HCV and pain, highlighting current knowledge as well as methodological issues that exist in many studies. We also present preliminary findings from a survey conducted at two Department of Veterans Affairs facilities to assess the scope and impact of pain on functioning in veterans with HCV. Our results indicate that pain is very prevalent within this population and that HCV-positive veterans who experience persistent pain have significant depressive symptoms and engage in high-risk behaviors, such as cigarette smoking and alcohol use. Finally, we draw upon our review and preliminary results to propose areas of future rehabilitative research and to address the implications for clinicians working with patients with comorbid HCV and pain.

PMID: 17551875 [PubMed - in process]

A closer look at pain and hepatitis C Preliminary___[J Rehabil Res Dev_ 2007] – PubMed Result

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Functioning in individuals with chronic fatigue syndrome: increased impairment with co-occurring multiple chemical sensitivity and fibromyalgia.

1: Dyn Med. 2007 May 31;6(1):6 [Epub ahead of print]

Brown MM, Jason LA.

ABSTRACT: BACKGROUND: Chronic fatigue syndrome (CFS), multiple chemical sensitivity (MCS), and fibromyalgia (FM) commonly co-occur. Some propose that CFS, MCS, and FM are manifestations of the same illness based on high rates of co-occurrence and overlapping diagnostic criteria. This study seeks to differentiate these diagnoses by comparing individuals with one or more illness on functioning, psychiatric comorbidity, coping style, and in vivo physical measures.

METHODS: Participants included 114 men and women who met criteria for CFS. FM was diagnosed during a physical examination, and MCS was assessed using a questionnaire. Participants were divided into four groups: CFS alone, CFS-MCS, CFS-FM, and CFS-MCS-FM. Self-report measures, a psychiatric interview, and in vivo physical measures were given.

RESULTS: 43.9% met criteria for CFS alone, 23.7% met criteria for CFS-MCS, 15.8% met criteria for CFS-FM, and 16.7% met criteria for CFS-MCS-FM. The CFS-MCS-FM group was more disabled than the CFS alone group on measures of physical functioning, general health, and bodily pain. In vivo measures did not differ, but the CFS-MCS-FM group rated exertion higher than the CFS alone group.

CONCLUSIONS: Individuals with CFS alone were the highest functioning group across several domains, such as disability, depression, and severity of symptoms. Participants with three diagnoses experienced the greatest amount of disability. While substantial co-occurrence of these illnesses was found, this study provides evidence that having more than one illness exacerbates one’s disability beyond CFS alone.

PMID: 17540028 [PubMed - as supplied by publisher]

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The effect of acclydine in chronic fatigue syndrome: a randomized controlled trial.

1: PLoS Clin Trials. 2007 May 18;2(5):e19.

The GK, Bleijenberg G, van der Meer JW.

Department of General Internal Medicine, Nijmegen Expert Centre Chronic Fatigue, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands.

OBJECTIVES: It is unclear whether insulin-like growth factor (IGF) function is involved in the pathophysiology of chronic fatigue syndrome (CFS). Unpublished data and reports in patient organization newsletters suggest that Acclydine, a food supplement, could be effective in the treatment of CFS by increasing biologically active IGF1 levels. Here we aimed to measure the IGF1 and IGF binding protein (IGFBP) 3 status of CFS patients compared to age- and gender-matched neighborhood controls, and to assess the effect of Acclydine on fatigue severity, functional impairment, and biologically active IGF1 level (IGFBP3/IGF1 ratio).

DESIGN: A randomized, placebo-controlled, double-blind clinical trial. SETTING: Radboud University Nijmegen Medical Centre, The Netherlands. PARTICIPANTS: Fifty-seven adult patients who fulfilled the US Centers for Disease Control and Prevention criteria for CFS. IGF status of 22 CFS patients was compared to that of 22 healthy age- and gender-matched neighborhood control individuals.

INTERVENTION: Acclydine or placebo for 14 wk.

OUTCOME MEASURES: Outcomes were fatigue severity (Checklist Individual Strength, subscale fatigue severity [CIS-fatigue]), functional impairment (Sickness Impact Profile-8 [SIP-8]), and biologically active IGF1 serum concentrations. Analyses were on an intention-to-treat basis.

RESULTS: There was no difference in IGF status in 22 CFS patients compared to healthy age- and gender-matched control individuals. Treatment with Acclydine did not result in significant differences compared with the placebo group on any of the outcome measures: CIS-fatigue +1.1 (95% CI -4.4 to +6.5, p = 0.70), SIP-8 +59.1 (95% CI -201.7 to +319.8, p = 0.65), and IGFBP3/IGF1 ratio -0.5 (95% CI -2.8 to +1.7, p = 0.63).

CONCLUSION: We found no differences in IGF1 status in CFS patients compared to healthy matched neighborhood controls. In addition, the results of this clinical trial do not demonstrate any benefit of Acclydine over placebo in the treatment of CFS.

PMID: 17525791 [PubMed - in process]

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