Robert Bennett, MD, PhD, FRCP, FACP, FACR, is Professor of Medicine and Nursing Research at Oregon Health and Science University (OHSU) in Portland, Oregon. He was born and educated in England, and did his basic rheumatology training with Professor Eric Bywaters at the Royal Postgraduate Medical School in London. He has lived in the USA since 1972 and did additional training with Professor Daniel McCarty at the University of Chicago. He was Chairman of the Division of Arthritis and Rheumatic Diseases at OHSU for 24 years (1976-2000). Dr. Bennett is a past President of the International Myopain Society and the American College of Rheumatology Western Region. He and his colleagues at OHSU have been actively involved in fibromyalgia research since 1980. Dr. Bennett has published over 400 articles and book chapters.
Oregon Health & Science University
Stephen I. Katz, MD, PhD is Director of the National Institute of Arthritis and Musculoskeletal and Skin Diseases at the National Institutes of Health. He has held that position since 1995. Concurrently, since 2001, he serves as Senior Investigator with the Dermatology Branch of the National Cancer Institute, NIH.
Dr. Katz completed his BA at the University of Maryland, his MD at Tulane University School of Medicine and his PhD in Immunology at the University of London. He completed his Dermatology residency at the University of Miami School of Medicine. Prior to becoming Director at NIAMS/NIH, he served as Marion B. Sulzberger Professor of Dermatology at the Uniformed Services University of the Health Sciences, and served two years as Acting Chairman of the Dermatology Department. For over twenty years he served as the Chief of the Dermatology Branch, National Cancer Institute, NIH.
From 1997-2002, Dr. Katz served as President of the International Committee for Dermatology and International League of Dermatological Societies. He is a member of the Institute of Medicine of the National Academy of Sciences and the American Academy of Dermatology and has held offices in these organizations and others throughout his career. Dr. Katz has received honors and awards for his service from professional, academic, non-profit and government entities nationally and internationally.
Dan S. Heffez, MD is a neurosurgeon in practice at the Milwaukee Neurological Institute in Milwaukee, Wisconsin. Prior to relocating to Milwaukee, he was Associate Professor of Neurosurgery, Rush Presbyterian St. Luke’s Medical College, Associate Neurosurgeon Rush Presbyterian St. Luke’s Medical Center and director of the Chicago Institute of Neurosurgery and Neuroresearch Neurovascular Surgery Center. He came to the Institute in 1990 from the Johns Hopkins School of Medicine, Baltimore, Maryland, where he served as an assistant professor of neurosurgery and honed his expertise in the treatment of cerebrovascular disorders. Prior to his work at Johns Hopkins, Dr. Heffez held a Fogarty Research Fellowship at the National Institute of Neurological and Communicative Disorders and Stroke.
The recipient of many honors and awards including the prestigious Johns Hopkins School of Medicine Clinician Scientist Award, Dr. Heffez is highly regarded for his surgical skill as well as his research efforts to advance the understanding and treatment of Chiari malformation, cervical myelopathy and cerebral vasospasm. Experimental work initiated and performed by Dr. Heffez was the impetus for developing human fetal surgery for the correction of certain forms of spina bifida. Since 1994 he has been exploring the link between cervical myelopathy and the fibromyalgia syndrome.
Dr. Heffez holds memberships in numerous professional organizations including the American Association of neurological Surgeons, Cerebrovascular and Pediatric sections; Congress of Neurological Surgeons; and Royal College of Physicians and Surgeons of Canada.
Milwaukee Neurological Institute
THE FIBROMYALGIA SYNDROME: OUTCOMES AND IMPLICATIONS
Context: Cervical myelopathy and fibromyalgia are associated with very similar symptoms. Some patients with fibromyalgia also exhibit the neurological signs of cervical myelopathy.
Objective: To determine if treatment of cervical myelopathy in patients with fibromyalgia improves the symptoms of fibromyalgia and the patients’ quality of life.
Design: A non-randomized, prospective, case control study comparing the outcome of surgical versus non-surgical treatment of cervical myelopathy in patients with fibromyalgia.
Setting: Single neurosurgeon referral practice.
Patients: 40 surgical and 31 non-surgical patients 18 years and older who carried the diagnosis of fibromyalgia and who had objective evidence of cervical myelopathy due to cervical spinal stenosis or tonsillar ectopia.
Main Outcomes: SF-36, Screening test for Somatization, HADS, MMPI-2 scale 1 (Hypochondriasis), and self-reported severity of symptoms at time of initial evaluation and one year after treatment.
Results: There was no significant difference in initial clinical presentation or demographic characteristics between the patients treated by surgical decompression and those treated by non-surgical means. There was a striking improvement in all symptoms attributed to the fibromyalgia syndrome in the surgical patients but not in the non-surgical patients at one year following the treatment of cervical myelopathy. At the one year follow-up, there was a statistically significant improvement in both physical and mental quality of life as measured by the SF-36 score for the surgical group as compared to the non-surgical group (Repeated Measures ANOVA p<0.01). There was statistically significant improvement in the scores from Scale 1 of the MMPI-2 and the Screening Test for Somatization Disorder, and the Anxiety and Depression scores exclusively in the surgical patients, (Wilcoxon signed rank, p<0.001)
Conclusion: The surgical treatment of cervical myelopathy due to spinal cord or caudal brainstem compression in patients carrying the diagnosis of fibromyalgia can result in a significant improvement in a wide array of symptoms usually attributed to fibromyalgia with attendant measurable improvements in the quality of life. We recommend detailed neurological and neuroradiological evaluation of patients with fibromyalgia in order to exclude compressive cervical myelopathy, a potentially treatable condition.
Additional authors: Ruth E. Ross, PhD, Yvonne Shade-Zeldow, PhD, Konstantinos Kostas, PhD, Mary Morrissey, ScD, Dean A. Elias, MD, Alan Shepard, MD.
Patrick B. Wood, MD attended medical school and completed residency training in Family Medicine at LSU Health Science Center in Shreveport, Louisiana. Following his residency, he undertook an additional research fellowship in Psychopharmacology and Neuroimaging within the LSU Department of Psychiatry. As a result of his research in fibromyalgia, he was recognized by the National Institutes of Mental Health as one of the nation's most promising New Investigators. He currently runs a Fibromyalgia Specialty Clinic and enjoys appointments to the Departments of Family Medicine, Anesthesiology and Psychiatry.
Department of Family Medicine
A majority of the symptoms that characterize the Fibromyalgia Syndrome suggest supraspinal pathology, including non-nociceptive pain, cognitive dysfunction, dysautonomia and temporospatial dysmetria. Fibromyalgia has previously been described as a ‘stress-associated’ disorder due to its frequent onset and exacerbation of symptoms in the context of stressful (physiological and/or psychosocial) life-events. The hippocampus is exquisitely sensitive to a variety of stress-related neurohormonal factors, and serves to regulate higher brain activity in response to stress exposure. Regulation of mesolimbic dopamine numbers among the many functions of the hippocampus. Exposure to stress has been demonstrated to disrupt mesolimbic dynamics in preclinical models, and stress is known to exacerbate clinical disorders in which dopamine plays a central role, including Parkinsons Disease, Attention-Deficit/Hyperactivity Disorder and Restless Legs Syndrome. We have recently demonstrated a disruption of mesolimbic function in Fibromyalgia Syndrome. A disruption of mesolimbic dopamine, due in part to the impact of stress on hippocampal function, serves as a reasonable explanation for a host of clinical and investigational phenomena that are associated with Fibromyalgia.
Misha-Miroslav Backonja, MD completed his neurology residency at the University of Wisconsin Medical School and then went on to multidisciplinary pain fellowship training also at UW Medical School, during which he started his research training. Following the fellowship he accepted a faculty position at the University of Wisconsin Medical School and a staff physician position at the University of Wisconsin Pain Clinic. Dr. Backonja’s clinical and research interest has been neuropathic pain. First he conducted a series of studies in the laboratory using neuropathic pain models, He then went on to conduct clinical research, investigating neuropathic pain mechanisms and conducting trials with newer pharmacological therapies. His research resulted in many publications in peer reviewed journals including Pain, Analgesia & Anesthesia, Neuroscience, Clinical Journal of Pain, Journal of Pain and Brain Research, just to mention a few. Dr. Backonja served on many research and review committees, including funding US national agencies such as NIH and international agencies, for example in Germany and Canada. His educational efforts lead to series of articles and book chapters, and he has made numerous didactic presentations at national and international meetings.
Quantitative measurements of neuropathic pain today include symptoms and signs, based on long tradition and recently developed tools and databases. With the results of those tools it is now possible to quantitatively measure neuropathic pain and symptoms at the bedside as well as in clinical trials.
Richard H. Gracely, PhD received his doctorate from Brown University in 1977. In 1974, he began working in what is now the Pain and Neurosensory Mechanisms Branch, National Institutes of Dental and Craniofacial Research, National Institutes of Health and was Chief of the Clinical Measurement and Mechanisms Unit and an adjunct member of the Department of Anesthesia, Georgetown University Medical Center. His research focuses on the neural mechanisms responsible for the pain abnormalities observed in chronic multi-symptom illness and in experimental models of these syndromes. Pain from clinical conditions, and pain induced in the laboratory, are assessed by subjective reports and by functional brain imaging using positron emission tomography (PET) and functional magnetic resonance imaging (fMRI). Dr. Gracely has published extensively in the field of pain and is an Associate Editor of the journal PAIN and an Editor of the Journal of Pain. He is currently a Professor of Internal Medicine, Division of Rheumatology, and of Neurology at the University of Michigan. Additionally he is a Research Health Science Specialist for the VA Ann Arbor Health System.
Fibromyalgia is defined by widespread pain and tenderness at 11 or more of 18 defined tender points. Current evidence indicates that tender points are not unique to fibromyalgia, and are simply regions in the body where all people are more tender. Using the number of painful tender points as a measure of tenderness is clinically expedient, but theoretically vulnerable to bias and influenced by subjective distress. Other means of assessing tenderness (e.g., pressure dolorimeter devices, or more elaborate psychophysical methods) demonstrate the same increased pain sensitivity in fibromyalgia that is noted with tender point assessments, but these measures are relatively independent of biasing factors or distress. Standard psychophysical procedures show that the level of blunt pressure needed to evoke a moderate level of pain in fibromyalgia patients is about half the level needed in healthy control subjects. When these levels of pressure, calibrated to produce moderate pain in each person, are delivered in an fMRI scanner, both patients and control subjects show similar levels of increased activity in a number of brain regions known to be involved in pain processing. When the lower pressures delivered to patients are delivered to control subjects, there is minimal activation, and a statistical comparison shows greater activity in patients in the same group of brain regions activated by moderately painful stimulation in each group. These regions include primary and secondary somatosensory cortex, insula, inferior parietal lobule, and cerebellum. These results using psychophysical and fMRI methods are consistent with a general centralized augmentation of mechanical pain sensitivity in fibromyalgia, and this augmentation may be a common feature of other pain syndromes such as idiopathic low back pain and pelvic disorders.
Manuel Martinez-Lavin, MD graduated as a physician from the National University of Mexico. He did his postgraduate training in Internal Medicine at St. Louis University in Missouri and in Rheumatology at Scripps Clinic in La Jolla, California. He is certified in Internal Medicine and Rheumatology by the American Board of Internal Medicine. He is currently Chief of the Rheumatology Department at the National Cardiology Institute of Mexico. He has published over 70 research articles in scientific, peer-reviewed journals. His research proposes that fibromyalgia is an autonomic nervous system disease, and a sympathetically-maintained neuropathic pain syndrome.
National Institute of Cardiology
The Autonomic Nervous System (ANS) is our vital structure for internal equilibrium and external adaptation. The peripheral autonomic system is divided into two branches; sympathetic and parasympathetic. These two divisions have antagonistic actions on most bodily functions and thus their proper balance preserves equilibrium.
With the use of a new cybernetic technology named heart rate variability analysis, different groups of investigators have consistently shown that fibromyalgia (FM) patients have changes consistent with ongoing sympathetic hyperactivity. This sympathetic hyperactivity is accompanied by hypo-reactivity to stress. Such autonomic malfunction provides a new coherent explanation for the multifaceted fibromyalgia features including its main manifestation; chronic widespread pain.
We propose that FM is a widespread neuropathic pain syndrome: It is a stimuli-independent pain state accompanied by allodynia and paresthesias. There are signs of central nervous system sensitization. Central sensitization is expression of neuroplasticity and is the major cause of hypersensitivity to pain after injury.
Among neuropathic pain causes we suggest that FM is a “sympathetically maintained,” based on the following arguments: The ongoing sympathetic hyperactivity. FM pain is responsive to sympathetic blockade, and FM pain is rekindled by norepinephrine injections.
This different perspective on FM opens new avenues for research and treatment.
Roland Staud, MD served his residency in clinical Pharmacology at Klinkum Steglitz of Freie Universität in Berlin, Germany. He completed his Internal Medicine residency at Klinikum Charlottenburg of Freie Universität. Later Dr. Staud was a Teaching Assistant of Medicine at Freie Universität School of Medicine. For several years he was in private practice and then completed his residency in Internal Medicine at Englewood Hospital in New Jersey. After service as Chief Resident of Internal Medicine at Englewood Hospital he completed his Fellowship in Rheumatology at New York University. In 1992, Staud became an Assistant Professor of Medicine in the Division of Rheumatology and Clinical Immunology at the University of Florida where he is now a Professor of Medicine.
In 2005 Dr. Staud received a College of Medicine Research Award from the University of Florida. In 2002 and 2001 he received the American College of Rheumatology REF Achievement Award and in 2001 he also received the ACR Service Award and the American Medical Association Physician’s Recognition Award. He is the member of several Professional Associations including the American College of Rheumatology, American Pain Society and International Myopain Society. In 2003 he helped write the Fibromyalgia Guidelines for the American Pain Society. From 2001 to present he has served on the Arthritis Foundation Advisory Committee. In 2005 began serving as a grant reviewer for The Wellcome Trust. He holds a patent on materials and method for the detection and treatment of Wegener’s granulomatosis. He has been an invited speaker at many national medical meetings and is currently a reviewer for several medical journals. He serves as an editor for Pain and Eur. J. Pain, as well as several other magazines. His published books and book chapters include Fibromyalgia for Dummies, a book he co-authored, and chapters Fibromyalgia in the Neurobiology of Chronic Muskuloskeletal Pain.
Dr. Staud is well published with chapters in eight scientific/technical books, co-authorship of Fibromyalgia for Dummies, a patient-focused text, and more than seventy-six articles in refereed journals.
Current research NIH funded studies include Mechanisms of Pain in Patients with Fibromyalgia Syndrome and Sex and Menstrual Cycle effect on Pain and Analgesia. Previous supported studies have looked at the mechanisms of pain in FM.
University of Florida
The generalized hypersensitivity associated with fibromyalgia (FM) has focused considerable interest on central mechanisms for the disorder. These include central sensitization, central disinhibition and a dysfunctional hypothalamic–pituitary–adrenal (HPA) axis. However, the central effects associated with FM may be directly related to a peripheral source of pain. Chronic nociceptive input induces central sensitization, magnifying pain, and it activates the HPA axis and the sympathetic nervous system. Chronic sympathetic activation indirectly sensitizes peripheral nociceptors and sets up a vicious cycle. Thus, it appears that central mechanisms of FM pain may be dependent on abnormal peripheral input(s) for development and maintenance of this condition
Alice A. Larson, PhD graduated from the University of Minnesota with a BA in Biology in 1972 and a PhD in Pharmacology in 1977. She studied electrophysiological techniques as a postdoctoral associate at the University of Illinois until 1978 when she was hired as an assistant professor of pharmacology and neuroscience at the University of Minnesota. Since then she has been promoted to full professor in the Department of Veterinary and Biomedical Sciences. She was awarded the SmithKline Beecham Award for Research Excellence (1994), served as a member of the Behavioral Neurobiology Subcommittee Study Section at NIMH (1988-1992), and served as Director of the Graduate Program in Neuroscience at the University of Minnesota (1992-95). Her research focuses on pain pathways, an area in which she has over 130 publications in a variety of scientific journals. University of Minnesota
Department of Veterinary and Biomedical Science
The primary complaint of patients with fibromyalgia is an enhanced sensitivity to pain (hyperalgesia) and spontaneous pain upon movement that should not normally be painful. This hyperalgesia probably originates in the brain, because it occurs in the absence of obvious pathology in the periphery and because it’s associated with other physiological changes that are regulated in the brain (e.g., abnormal stress responses and non-restorative sleep). We know a lot about various neurochemicals in the brain that cause hyperalgesia, but not much about the exact cells involved. Our working hypothesis is that hyperalgesia is modulated in the central nervous system by mast cells, immune cells whose activity and distribution are strongly correlated with many models of hyperalgesia.
In the periphery, mast cells are commonly found along nerves, where they are well known to release neuroactive substances that sensitize peripheral nerves. In the periphery, there is cross-talk between nerves and the adjacent mast cells that modulates pain-related (nociceptive) sensitivity. Mast cells exert their influence by increasing their numbers in a specific tissue and/or by degranulating. Degranulation causes compounds to be released from mast cell granules, and many of these compounds have immediate neuroactive and/or vasodilatory effects. The cross-talk occurs when nerves transmitting pain messages are activated by noxious, painful stimuli and release potent degranulators of mast cells, such as substance P. The mast cells, in turn, degranulate and release compounds that further sensitize peripheral nerves, causing hyperalgesia.
Mast cells are also located in the central nervous system, but less is known about their activity in the brain. Interestingly, mast cells in the brain are distributed almost exclusively in the thalamus. The thalamus is important in arousal, chronic stress, and the integration of sensory information including tactile and nociceptive input. Mast cell distribution in the thalamus of normal healthy mice, humans, and other mammals appears in several thalamic nuclei, is sparse, uneven, and varies greatly in number and distribution from one individual to another. Because mast cells in the brain are located in thalamic nuclei that play important roles in pain processing, and because pain-sensitive neurons projecting from the spinal cord to the thalamus contain compounds capable of degranulating mast cells, there exists the intriguing possibility that mast cells in the thalamus might influence pain, similar to their role in the periphery.
Two situations well known to exacerbate pain are the presence of certain reproductive hormones and exposure to stress—these situations are also known to influence mast cell number and activity. Since females are generally more sensitive than males to painful stimuli, we explored the differences between genders regarding mast cells and the sensitivity to mechanical stimuli in a model of hyperalgesia. Our results showed that in normal mice, the difference between mast cell distribution in males and females was especially pronounced in those thalamic nuclei that process nociceptive signals. When we induced mechanical hyperalgesia by ligating a spinal nerve in mice, females were more prone to hyperalgesia than males. In addition, females accumulated more thalamic mast cells in response to the spinal nerve ligation than did males, and the mast cells were more densely distributed on the side of the thalamus to which the ligated nerve projected. In subsequent studies, we found several additional lines of evidence showing correlations between various types of hyperalgesia, increases in mast cell numbers, and mast cell degranulation. For example, when mice were injected with NGF, a hyperalgesic compound that is elevated in the cerebrospinal fluid of patients with primary fibromyalgia, thermal hyperalgesia corresponded well with the incidence of mast cell degranulation.
While these and the spinal nerve ligation studies indicate a correspondence between mast cells and enhanced pain, they do not prove a cause and effect relationship. Therefore, to investigate whether the degranulation of mast cells in the thalamus causes hyperalgesia, we used a drug that prevents mast cell degranulation. When injected into the brain area, this mast cell stabilizer prevented the hyperalgesic condition that normally would have been produced by a large dose of dynorphin, another compound that is elevated in the cerebrospinal fluid of patients with fibromyalgia. In other models of pain in mice, we found that a centrally injected mast cell stabilizer also inhibited behaviors that are thought to reflect pain. Together these data support the possibility that the transmission of pain is modulated by mast cell degranulation in the thalamus.
Based on these data, we believe that mast cells in the thalamus influence pain processing in the central nervous system, similar to mast cells’ well-characterized effect peripherally. If this is the case, it would shed valuable light on a variety of symptoms of the fibromyalgia syndrome, such as abnormal stress responses and sleep disorders since they also depend on neuronal pathways that pass through the thalamus. Thalamic mast cells may be the common link explaining several diverse symptoms of fibromyalgia.
For details, please refer to the following:
Kim Dupree Jones, RN, FNP, PhD is an Assistant Professor at the Oregon Health and Science University Schools of Nursing and Medicine. She received her BSN degree from the University of Tennessee, her MN in Nursing/FNP at Emory University and her PhD and Post-Doctorate at Oregon Health and Science University. Currently she is the Assistant Professor, Primary Health Care Nurse Practitioner Programs at Oregon Health & Science University School of Nursing. Prior to her tenure at OHSU, she was an Assistant Professor at Georgia State University in the Family Nurse Practitioner Program. Dr. Jones is a Board member of the Oregon Fibromyalgia Foundation, and serves as Foundation president in 2005-2006.
Dr. Jones’ most current published papers include work with Dr. Robert Bennett’s fibromyalgia group at OHSU. Currently, she is involved with funded studies looking at exercise and balance in fibromyalgia . She continues to be funded for research related to growth hormone in fibromyalgia research, including current research looking at treatment with an oral growth hormone secretogogue, and research studying pyridostigmine bromide and exercise in FM patients. The GH stimulating effect of this drug is impressive and far more cost effective than growth hormone.
Schools of Nursing and Medicine, SN-5S
PURPOSE: Clinicians report that fibromyalgia (FM) patients have balance impairments, yet this has never been objectively tested. The purpose of this study was to determine whether patients with FM differ from matched healthy controls in their subjective and objective balance control, using a recently validated tool to determine the extent of balance disturbance.
METHODS: 28 FM subjects (age 49.0 +/- 4.3) and 33 healthy controls (age 47.6 +/- 5.8) underwent objective balance testing with The Balance Evaluation-Systems Test (BESTest). All subjects were free from conditions associated with poor balance such as neuropathy and vestibular disorders. The BESTest was designed to identify impaired subcomponents of balance: Stability Limits, Transitions/Anticipatory Postural Adjustments, Reactive Postural Responses, Sensory Orientation, and Stability in Gait with selective attention. Scores for the total test and subsections are provided as a percentage of total possible points. Subjective balance was evaluated with the Activities-Specific Balance Confidence Scale (ABC). This is a 16-item questionnaire designed to identify fear of falling by providing level of confidence (0¬100%) with which participants can form specific tasks without losing balance. We also asked subjects to report the number of falls in the previous six months prior to testing.
RESULTS: FM patients scored significantly worse on both objective and subjective measures of balance compared to controls. The composite BESTest score was M = 87% in the FM patients and M = 95% in the controls (p <.001). The FM subjects were different from controls in 4 of the 5 components of the BEST test: Stability Limits (p < .001), Transitions/Anticipatory Postural Adjustments (p = .007), Sensory Orientation (p <.012), and Stability in Gait with selective attention (p <.001). FM subjects were also significantly different from controls in ABC self-report (FM M = 78% balance confidence, healthy controls M = 98% confidence, p <.001). FM subjects reported 25 falls in the last 6 months whereas controls reported 5 falls (p =.01). The correlation between ABC and BESTest scores was significant (r = 0.64).
CONCLUSIONS: FM is associated with balance problems and increased fall frequency. Four of five subcomponents of the BESTest were abnormal in FM subjects consistent with the hypothesis that FM affects many peripheral and central mechanisms for postural control. Furthermore, the subjects are well aware of their balance deficits reflected in their low balance confidence. Particularly striking was their inability to use somatosensory information to identify their limits of stability, use anticipatory postural adjustments and maintain gait speed under cognitive distraction. Further study is needed to identify the relative contribution of neural and muscular impairments to postural stability in patients with FM and develop specific balance interventions to remediate these impairments. Acknowledgement: 2 R37 AG006457-19 NIH/NIA (Kim D. Jones, Fay B. Horak, Kerri Winters, Robert M. Bennett Oregon Health & Science University, Portland, OR)
Dedra S. Buchwald, MD received her BA in Neurobiology and Medical Degree from the University of California in San Diego. She completed an internship in Internal Medicine at North Carolina Memorial Hospital, Chapel Hill and her residency in Internal Medicine at Duke University Medical Center. Following she spent three years as the Henry J. Kaiser Fellow in General Internal Medicine at Harvard Medical School, Brigham and Women’s Hospital in Boston.
Buchwald joined the faculty at the University of Washington in 1987 and is currently a Professor of Medicine. She is the Director of the Chronic Fatigue Clinic at Harborview Medical Center in Seattle. In addition to her School of Medicine teaching responsibilities, she serves on the Faculty of the University of Washington Multidisciplinary Clinical Research Training (K-12) Program, is the Director of the Native Investigator Development Program, Director of the University of Washington Twin Registry and serves as a member of the Institute of Medicine, Committee on the Health of Gulf War Veterans.
Dr. Buchwald serves as principal investigator, co-investigator and mentor on many on-going research studies funded by the NIH and other organizations in the areas of chronic pain, fibromyalgia, chronic fatigue. Additionally, she is very active in research studies specific to the Native American population. Dr. Buchwald has published over 165 articles in refereed journals and 12 book chapters, as well as other publications. She is a regular presenter on chronic fatigue syndrome and fibromyalgia in the US, Canada and Europe.
Department of Medicine
Michael J. Rosner, MD received his undergraduate degree in Physiological Psychology at the University of Virginia (with Honors) in 1969. He graduated with his MD from the Medical College of Virginia in 1972 where he also completed a straight Surgical Internship and Neurosurgical residency. He spent six months during 1977 at the Institute for Neurological Sciences at the Southern General Hospital in Glasgow, Scotland working as a registrar in Neurological Surgery.
His first faculty appointment was in the Division of Neurosurgery at the Medical College of Virginia as an Assistant Professor of Neurological Surgery and assistant chief of Neurosurgery at McGuire Veterans Medical Center. He was elected to fellowship in the American College of Surgeons. While in Richmond, he began research in the field of Neurotrauma and focused upon therapy for Traumatic Brain Injury and especially intracranial hypertension. He received grant funding by NIH and the Veterans Administration. It was here that he made early observations on the relationships between Cerebral Perfusion Pressure (CPP) and intracranial pressure waves.
He was recruited as an Associate Professor of Neurosurgery to the University Of North Carolina School Of Medicine at Chapel Hill by Dr. Steve Mahaley in 1983. He became medical director of the Neurosurgical ICU and continued with work in Traumatic Brain Injury and Neurosurgical Critical Care. He was granted tenure.
When Dr. Mahaley took over the Division of Neurological Surgery at the University of Alabama he again recruited Dr. Rosner to be Medical Director of the Neurosurgical Intensive Care Unit at University Hospital. While at UAB he was promoted to full professor with tenure and he became Chairman of the American Association of Neurological Surgeons Neurosurgery Critical Care Course. As a direct result of research in TBI, the mortality and morbidity of severe brain injury have been halved. He is an eminent authority on Cerebral Perfusion Pressure, is widely published and a popular speaker. In 1995, he became a fellow of the American College of Critical Care Medicine. In 1998, Dr. Rosner left the University of Alabama for private practice.
His research interest and publications center on Cerebral Perfusion Pressure as related to Traumatic Brain Injury. At the 1991 Eighth International Symposium on Intracranial Pressure in Rotterdam, Dr. Rosner received awards for presentations on “Cerebral Perfusion Pressure Management of Head Injury” and “Toxic Effects of Nutritional Support in the Severely Head Injured Patient” as well as the best paper of the symposium.
His experience with TBI and spinal cord injury led to his current interests in the narrow spinal canal and hypoplastic posterior fossa (Chiari). These interests began to develop in the early 1980’s and have grown in importance to Dr. Rosner’s practice. In the mid-1990’s Dr. Rosner became aware of the frequency with which many patients with Chiari and cervical stenosis had been diagnosed with fibromyalgia, but also noted that their overall complaints markedly improved with treatment of the spinal and posterior fossa decompression. This area of interest remains paramount to Dr. Rosner’s clinical practice today.
80 Doctors Drive, Suite 4
Understanding the association between Chiari malformation and fibromyalgia requires multiple distinct leaps in the general understanding of Chiari malformation and its neurological effects:
ii. Long term, it is complicated by secondary degenerative changes in the spine due to abnormal spinal mechanics from muscle weakness and postural abnormalities. Treating these secondary changes without understanding the underlying pathophysiology is usually unhelpful or worsens the symptomatology.
ii. Altered processing with allodynia, wind-up, failure of habituation and inhibitory processes with sensory threshold change.
iii. Secondary spinal degenerative changes with root & cord compression.
ii. Sleep disorders
iii. Attention disorders & others
ii. Maladaptation due to chronic illness & social stress
iii. Drug dependency
This talk will provide an overview with examples of the above including outcomes from surgical treatment. It will be stressed that those with Chiari and its related syndromes usually have a very complex disease which has been present for decades. Its polysomatic nature and frequent maladaptive behaviors can stress the diagnostic acumen and tolerance of many physicians easily leading to misdiagnosis or concerns of malingering and psychosomatic disorders.
Andrew J. Holman, MD has been a clinical rheumatologist for 15 years in south suburban Seattle and is also Assistant Clinical Professor of Medicine at the University of Washington. He completed his undergraduate studies at Bowdoin College in 1981 and received his medical degree from the University of Missouri-Columbia in 1987. His internal medicine residency training was completed at Denver Presbyterian Medical Center in 1990.
His interests in fibromyalgia, autoimmune disease and the autonomic nervous system has lead to development of a treatment strategy for fibromyalgia with dopamine agonists and investigation into how autonomic regulation influences autoimmunity. Dr. Holman’s hypothesis that autonomic arousal from deep, restorative sleep underlies the pathogenesis of fibromyalgia led to American College of Rheumatology poster presentations in 1998-2000 describing the use of Restless Legs Syndrome options for fibromyalgia. Ultimately, this work led to use of dopamine agonists for fibromyalgia and placebo controlled trials to support this hypothesis.
Comorbidities able to increase sympathetic tone, such as untreated obstructive sleep apnea, has lead to new efforts to discover and negate any adverse effect on autonomic tone in patients with FMS. In animal models, positional, intermittent cervical cord compression has been proposed as a cause of central autonomic dysregulation. Consequently, diagnosis and treatment of this emerging new entity in humans has become a particularly important focus of his recent research efforts.
Pacific Rheumatology Research, Inc.
Two Chiari malformations were identified and 56 cases of cord compression were found at C2-3, C3-4, C4-5, C5-6, C6-7 and C7-T1, of which, 42 (75%) required the novel extension view for diagnosis. For 8 patients, cord flattening was present, but only appreciated in the extension view. ICCC patients trended higher in MHAQ pain, fatigue, global, but lower in psych and stiffness scores without achieving statistical significance. Screening questions were helpful, but only positive romberg (p=0.056) and pain in a hairdresser sink (p=0.072) approached significance by Pearson correlation. However, positive romberg correlated with disability (.004), narcotic use (.009), pain in hairdresser sink (.0001) and dentist chair (.0001), dizziness (.043), tender point count (.0001), and cervical pain with extension (.0001).
Roger W. Kula, MD is a graduate of Johns Hopkins University. He trained at New York and Memorial Hospitals, Cornell University, New York where he interned in Medicine and Assistant Physician and Fellow in Medicine. He completed his residence in Neurology at HC Moffitt and University of California Hospitals, San Francisco, California. Dr. Kula served the Public Health Services at the Medical Neurology Branch of the NINCDS, Bethesda, MD, where he received his neuromuscular disease training under Dr. W. King Engel.
Dr. Kula joined SUNY-Health Sciences Center at Brooklyn in 1977 as Assistant Professor in the Department of Neurology and Director of the Neuromuscular Disease Unit. He is widely published and the recipient of several grants. In 1998, Dr. Kula was presented with the Ade T. Milhorat, MD Humanitarian Award by the Muscular Dystrophy Association.
Recently, Dr. Kula joined Dr. Thomas Milhorat in establishing The Chiari Institute in Great Neck, New York. Since 1984, Dr. Kula has been Associate Professor of Clinical Neurology and in 1988 became Vice Chairman of the Department of Neurology and Chairman of the Education and Clinical Services Committee. He joined the Long Island College Hospital medical staff as Chairman in 1992.
Board Certified in Internal Medicine and Neurology, Dr. Kula has played an active role in the American Academy of Neurology, the Brooklyn Neurological Society and the Medical Club of Brooklyn. Dr. Kula is a medical advisor for the Muscular Dystrophy Association and an active member with the American College of Physician executives, as well as the American Society of Clinical Neurophysiology and the American Association for the Advancement of Science.
The Chiari Institute
Patients with CMI may experience no symptoms. When symptoms are present, they usually do not appear until adulthood. Most patients complain of severe pressure-like occipital headache and neck pain but may also experience: Dizziness, disequilibrium, tinnitus, chronic fatigue, tenderness, numbness, tingling, burning, sleep apnea, palpitations, tremors, clumsiness, segmental pain, impaired memory or concentration, cervical pain, low back pain and urinary incontinence. Because of this complex symptomatology, patients are frequently misdiagnosed with illnesses such as fibromyalgia and chronic fatigue syndrome. At least one-fourth of patients manifest symptoms following relatively minor head or neck injury, complicating the understanding of their underlying disorder and raising issues of malingering or secondary litigious gain.
Specific radiologic criteria for the identification of tonsillar ectopia and CMI are fuzzy. Recent analyses of posterior fossa dimensions and subtle a abnormalities of CSF flow at the craniocervical junction may make it possible to more easily identify a hypoplastic posterior fossa (with only minimal or no tonsillar descent) sometimes referred to as Chiari zero. The most constant feature of MCI is a volumetrically small posterior fossa, which predisposes patients to hindbrain overcrowding.
The goal of the diagnostic work-up is to establish a correct diagnosis, separate possibly concurrent or associated clinical problems, provide a course of management and clearly lay out the risks, benefits, and expectations of possible operative intervention.
Timothy Wiebe, MD was born in Dawson Creek, British Columbia, Canada. He graduated with a degree in medicine from the University of Alberta in 1993; and from neurosurgical residency at the University of Mississippi in 2000.
Dr. Wiebe was inspired by his parents who were both active in health care. Prior to beginning at the university he volunteered with the Association for the Rehabilitation of the Brain Injured in Calgary, Alberta. He was inspired by ARBI Cofounder Audrey Morris—now recognized as Lady Audrey Morrice after decoration with the order of Canada for her contribution to brain injury rehabilitation.
Dr. Wiebe has become interested in clinical manifestations of mesenchymal hyperplasia as they may relate to formerly covert developmental spinal conditions.
Currently, Dr. Wiebe practices general neurosurgery for the Southern Neurological and Spinal Institute in Hattiesburg, Mississippi. His wife, Jacqueline A. Wiebe, MD is Director of Psychiatry and Student Counseling at the University of Southern Mississippi. Daughter Sheree Johnson currently attends Miami Advertising School.
Southern Neurological and Spinal Institute
At the 5 week stage of human embryology mesenchymal cells migrate diffusely, and their differentiation is guided by overlying ectoderm. (Brookes) A patient with multiple manifestations of mesenchymal hyperplasia has been reported; including torus palatinus, adult onset Bartter’s Syndrome, and fatty filum terminale with adult tethered cord syndrome. (Wiebe)
The author reviews manifestations of mesenchymal hyperplasia and concludes that clinical signs of mesenchymal hyperplasia may suggest underlying occult pathology; and that mesenchymal hyperplasia may have a diffuse pathogenic role.
Luc Dupont Jasmin, MD, PhD is currently involved in a clinical practice centered on the treatment of pain, epilepsy and spinal disorders. His current reseach activities are in the field of neuroanatomy and neuropharmacology of pain and inflammation. He uses a combination of molecular (gene transfer, RNAi), pharmacological, behavioral and anatomical approaches.
Dr. Jasmin received his Diploma of College Studies at C.E.G.E.P. Saint Laurent, in Canada. He received a Minor in Chemistry, Doctor of Medicine and PhD in Neuroanatomy from the University of Montreal in Canada. His Postdoctoral training internship in surgery and his residency in neurosurgery were completed at Notre-Dame Hospital at the University of Montreal, Canada. His postdoctoral training in research, anatomy, and his clinical work in neurosurgery were completed at the University of San Francisco.
His research credentials are extensive including several NIH funded investigations. Topics of research include, Cortically induced antinociception; Neurogenic Cystitis; A new therapeutic approach for breast leptomeningeal carcinomatosis; Noradrenergic dysfunction: a model of fibromyalgia pain; Cortical modulation of pain behavior; Sustained inhibition of pain behavior by increasing glutamic acid decarboxylase (GAD) expression in the Rostral Agranular Insular Cortex in the rat; Hyperalgesia in noradrenaline deficient mice; and Schwann cell spinal remyelination in the rat. Dr. Jasmin has also taken on the challenging task of developing a rat model for fibromyalgia scientific studies.
Dr. Jasmin is well published with more than thirty-six articles to his credit. He has also been involved with writing reviews, chapters and editorials for several medical journals. He is a frequent invited lecturer, including a presentation at the NIH/NIAMS Fibromyalgia Program Assessment meeting in 2002 and the National Fibromyalgia Research Association Symposium and NIH Fibromyalgia workshop in 2004. His accomplishments also include a 2002 patent application on therapeutic uses of tachykinin receptor antagonists and adrenenoreceptor antagonists on pain and opiate dependence. Dr. Jasmin has several abstracts that are currently under review for publication.
Department of Surgery
One of the most exciting recent discoveries in pain research is that interactions between neurons and glial cells are critically involved in the establishment and maintenance of complex pain syndrome. While many studies have now shown the importance of such interactions in the spinal cord, particularly in relation to pain associated with nerve injury, much less is known about the significance of neuron-glial cell relations in the periphery where primary sensory neurons are located.
The primary sensory neurons are the first neuron to sense painful stimuli and they are the ones damaged when there is a nerve injury. A unique type of glial cell, the satellite cell, surrounds each one of these neurons. Just as the neurons they surround, satellite cells undergo profound changes in chronic pain states. One of the key roles of satellite cells is to ensure that constant levels of ions potassium are maintained around neurons. This occurs through the uptake and release of extracellular potassium through satellite cells' ionic channels and redistribution of potassium between gap junctions between satellite cells. Neurons can directly affect these events by releasing neurotransmitters that reach satellite cells. It is likely that perturbation of the satellite cells or the communication between satellite cells and neurons, deeply impact the ionic equilibrium in the trigeminal ganglion and nerve injury pain. To study the influence of ionic changes on nerve injury pain, we alter the expression of specific genes (one at the time) in satellite cells using a novel technique name RNA interference (RNAi). Using this technique we are able to silence individual genes and observe the effect on behavior and molecular adaptations in the trigeminal ganglion. The genes that we target are potassium channels found on satellite cells only, gap junctions, and proteins on which neurotransmitters in the satellite cells. These studies serve to establish the importance of neuron-glial cell communication in chronic pain and to further our understanding on how possible variations molecular adaptation after nerve injury could underlie individual susceptibility to pain.
Serge Marchand, PhD received his doctorate in neuroscience from the faculty of medicine at Université de Montréal and a post-doc in neuroanatomy from USCF. He is professor at the faculty of medicine at Université de Sherbrooke, Director of the Pain Axis at the Clinical Research Center of the CHUS and has a joint chair in pain at both UQAT and Université de Sherbrooke. He is author of several articles and book chapters in the field of endogenous pain modulation mechanisms and of a book entitled « Le phénomène de la douleur » (Chenelière-McGraw-Hill, Montréal and Masson editors, Paris, 1998). His research interests aim at understanding the neurophysiological basis of the development, persistency and treatment of chronic pain.
Universit de Sherbrooke
The fibromyalgia syndrome is a common clinical condition with a complex clinical pattern characterized by widespread pain and by other clinical manifestations such as sleep disturbance, fatigue, depression, gastrointestinal symptoms and headache 3,16. The aetiology of fibromyalgia is still unknown. However, biochemical abnormalities in the cerebrospinal fluid of those patients, including low concentrations of the metabolites of serotonin (5HT) and noradrenalin (NA) 14, high concentrations of substance P 13,15,15 and of nerve growth factors 6 and a reduction of brain dopamine (DA) 17,18 suggest a pathogenesis of central origin. The reduction of 5HT, NA and DA is consistent with the idea that a dysfunction of the descending inhibitory systems is responsible, at least in part, for the widespread pain of fibromyalgia.
Pain is a dynamic phenomenon resulting from the activity of both inhibitory and excitatory endogenous modulatory systems12. One of these mechanisms, the diffuse noxious inhibitory control (DNIC)9,10, is activated by nociceptive stimuli and involves the activation of serotoninergic, noradrenergic, and opioidergic descending inhibitory pathways from the brainstem 2,5,9,10. In animals, lesion of the spinal dorsolateral funiculus (DLF), a pathway responsible for descending 5HT and NA inhibition, produces hyperalgesia 1.4 The reduction of 5HT and/or NA in certain chronic pain conditions raises the possibility that a deficit of DNIC is responsible for the experience of diffuse pain.
We developed a spatial summation paradigm to verify the recruitment of DNIC when different segments of the arm are immerged in nociceptive cold or hot water11. We recently demonstrated that the recruited inhibitory mechanism is opioidergic8, as it is the case for DNIC. Using the same paradigm we found that for fibromyalgic patients, no differences were found between the increasing and decreasing sessions; pain is always related to the surface stimulated, suggesting a lack of DNIC in these patients. Moreover, the deficit of DNIC found in fibromyalgia is not generalized to all chronic pain conditions since DNIC was normally activated in the low back pain patients7.
During this symposium, I will present some of our results showing a deficit of DNIC in fibromyalgia but not in LBP by using different paradigms that could be suitable in the clinical setting. I will also discuss some preliminary results on the role of sex hormones and the autonomic nervous system in fibromyalgia.
I. Jon Russell, MD, PhD is Associate Professor of Medicine at the University of Texas Health Science Center at San Antonio and Director of the University Clinical Research Center. Since joining the faculty at the University of Texas Health Science Center at San Antonio in 1978, Dr. Russell has served as a council member for the Central Region American College of Rheumatology, as National Chairman for the American College of Rheumatology's Non-articular Rheumatism Study Group, on the Research Grants Committee for the Arthritis Foundation, on the Research and Development Committee for the Audie Murphy Veterans Administration Hospital, on the Chronic Pain Management Subcommittee for the University Health System, and on several site review committees and grant review panels for the National Institutes of Health.
Dr. Russell has been honored by listings in The Best Doctors in America, The Best Doctors in America: Central Region, The Best Doctors in the South and Southwest, The Best 2000 Doctors in America and the international Faculty of 1000 Medicine. He was given the Humanitarian of the Year Award  by the South Central Texas Chapter of the Arthritis Foundation.
Dr. Russell has conducted research studies in the immunology, pathogenesis, and management of rheumatic diseases and fibromyalgia syndrome. His current research involves genetic and biophysiologic mechanisms of pain and stiffness in fibromyalgia syndrome. He is an author of over 100 original publications, including research reports and invited chapters in medical textbooks, and his research is reported in numerous lay articles.
He was Founding President of the International MYOPAIN Society and currently serves as a Board Member for that organization. He is a Senior Editor for the Haworth Press, and has been Editor-in-Chief of The Journal of Musculoskeletal Pain since its inception over 10 years ago. He is also an Editorial Board member for Pain Watch and several medical publications in the United States, Canada and France. He serves as a reviewer for several professional journals.
Dr. Russell is co-author of The Fibromyalgia Help Book, and producer of the video documentary "Fibromyalgia and You," two educational resources for people with fibromyalgia. He has also supported lay group education activities by serving on the boards of many fibromyalgia syndrome lay support organizations in the United States, Canada, France and the European Union. He travels extensively in the United States and abroad speaking to medical audiences and lay groups about soft tissue pain conditions, rheumatic diseases, and medical education issues.
University of Texas at San Antonio
Physiologic. That contention is based on the experimental findings of increased wind-up in the dorsal horn of the spinal cord and allodynia confirmed by functional magnetic resonance imaging of pain signaling in the brain.
Biochemical. Abnormalities in the cerebrospinal fluid [increased pronociceptors like substance P and nerve growth factor, plus decreased levels of antinociceptors evidenced by metabolites of serotonin, norepinephrine, and dopamine], abnormalities in the blood [tryptophan, serotonin, others] and abnormalities in the urine [5-hydroxyindole acetic acid] support the physiological observations. A formula based on spinal fluid neurochemical abnormalities appears to be objectively diagnostic.
Therapeutic. The treatment of FMS is increasingly directed at correcting the demonstrated abnormalities. An attempt to control substance P activity by blocking the neurokinin-1 receptor was not successful as monotherapy, but an alpha-adrenergic agonist reduced the spinal fluid levels of substance P. Efforts directed at augmenting biogenic amine agonists have produced four successful drugs with multidimensional benefits. Calcium channel blockade and activation of gamma-hydroxybutyrate have proven beneficial for both pain and sleep.
Conclusions. Neurochemical abnormalities in biological fluids obtained from patients with FMS are relevant to the symptoms exhibited by the patients, provide objective measures in support of a central nervous system pathogenesis, and have successfully served as guides to the development of more effective medicinal therapies.
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