2004 - New and Future Directions in Fibromyalgia Pain Management
This year’s symposium focus was on pain and the challenges faced by doctors in helping fibromyalgia patients. Presentations about evolving research on the etiology of fibromyalgia provided depth to understanding the challenges faced by both fibromyalgia patients and treating physicians.
Dr. Bennett is Professor of Medicine 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 currently the President of the International Myopain Society and is a past president of the American College of Rheumatology Western Region. His clinical research interests include fibromyalgia, systemic lupus erythematosus, and overlap syndromes. He and his colleagues developed the Fibromyalgia Impact Questionnaire in 1993; it is now the most widely used instrument for measuring disease activity in fibromyalgia patients. He was first to report adult growth hormone [GH] deficiency in a subset of fibromyalgia patients in 1992 and has subsequently shown the benefits of GH replacement. He holds patents for the utilization of GH in fibromyalgia, chronic fatigue syndrome, rheumatoid arthritis and polymyalgia rheumatica. His bench research involves the molecular characterization of cell surface DNA receptors and he was recently awarded a US patent for a related gene sequence. He has published over 350 articles and book chapters. He is/has been on the editorial boards of Pain, Arthritis and Rheumatism, Geriatrics, the Journal of Musculoskeletal Pain and the Journal of Functional Syndromes.
The rational management of chronic pain (CP) calls for a broad-based approach based upon a bio–psycho–social approach to management. A structured multidisciplinary approach to managing CP patients requires an appreciation of the parts that make up the whole. One cannot successfully manage CP patients if one treats the diagnosis of CP as a unified entity. There are 12 separate management issues that usually require attention in most CP patients seeking medical help which will be presented. They are: Education, Pain, Fatigue, Sleep, Psychological disorders, Endocrine dysfunction, Dysautonomia, Deconditioning, Cognitive dysfunction, The existential crisis, Association syndromes and Evaluating the response to treatment.
Dr. Staud 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 the 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. He became an Assistant Professor of Medicine in the Division of Rheumatology and Clinical Immunology at the University of Florida where he is now an Associate Professor of Medicine. 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. In 1996 he received the American College of Physicians Fellowship and in 1989-1990 the Pfizer: Good Physician Award. He is the member of several Professional Associations including the American College of Physicians and the American College of Rheumatology. Currently he is on the NIH ad hoc study section and in 2003 he helped write the Fibromyalgia Guidelines for the American Pain Society and served on the Food and Drug Administration Arthritis Advisory Committee. From 2001 to present he has served on the Arthritis Foundation Advisory Committee. 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. His publications include Fibromyalgia, a book he co-authored, and a chapter in the Neurobiology of Chronic Muskuloskeletal Pain. Dr. Staud is well published with more than fifty-five articles in print plus he is responsible for the creation of thirty-six abstracts both in print and through presentation at national medical meetings.
Many chronic pain syndromes, including fibromyalgia (FM), show evidence of central nervous system hyperexcitability related to central sensitization. Windup (WU) of second pain reflects increased excitability of spinal cord neurons that is related to central sensitization. Psychophysical testing can help characterize this important central nervous system phenomenon because of the parallels between electrophysiological WU and WU of second pain. Animal experiments have shown that once WU has been established, only low frequency tonic nociceptive input is required to maintain the sensitized state of dorsal horn neurons (WU-maintenance or WU-M). The stimulus frequency necessary to maintain the hyperexcitability of spinal cord neurons can provide a measure of central sensitization. Because central sensitization plays an important role in many chronic pain syndromes including FM, we compared WU-M in 72 normal controls (NC) and 104 FM subjects. WU of second pain was produced by a train of 0.7s duration thermal pulses applied to the glabrous surface of the hands at a frequency of 0.3 Hz. Enhanced second pain associated with WU could thereafter be maintained in FM but not NC subjects for up to 120s by stimuli delivered at 0.16 and 0.08 Hz (WU-M stimuli). These two frequencies of stimulation do not produce WU when delivered alone. Thus, unlike NC subjects, FM subjects showed enhanced second pain during WU-M stimuli at very low stimulus frequencies, indicating central sensitization. Increased WU sensitivity, enhanced WU-M, and increased WU-related aftersensations help account for persistent pain conditions in FM subjects. In addition to WU, WU-M appears to be a useful tool to study mechanisms of pain in patients with characteristics of central sensitization.
Dr. Krassioukov graduated from Volgograd State Medical School, Russia in 1979 and continued postgraduate training at the Ivan Pavlov Institute of Physiology, Academy of Science of the Soviet Union, in St. Petersburg, Russia. After successful completion of his PhD thesis he practiced neurology in Tallinn, Estonia. In 1991, through a Canada-USSR research exchange program he started his research career in North America. Presently, Dr. Krassioukov is Associate Scientist, ICORD, University of British Columbia, Vancouver, BC, Canada. He also holds a cross appointment at the Department of Physical Medicine & Rehabilitation at the University of Western Ontario, London, ON, Canada. Using experimental animal models and clinical investigations in humans, his research is focusing on investigation of the mechanisms of autonomic dysfunctions and pain after spinal cord injury. He has authored and co-authored more than 60 peer-reviewed manuscripts, book chapters and reviewed articles. Numerous international agencies such as Christopher Reeve Paralysis Foundation, Cervical Spine Research Society, Heart and Stroke Foundation of Canada, British Columbia Neurotrauma Fund/Rick Hansen Institute and others support his research. In July 2003, in order to achieve his goal to practice medicine in North America, Dr. Krassioukov started his residency training in Physical Medicine & Rehabilitation, at the University of British Columbia, Vancouver, Canada.
Chronic pain is a common feature of numerous clinical disorders including spinal cord injury (SCI) and fibromyalgia (FM). Recently, numerous clinical observations suggested the relationship between cervical spine injury and the development of FM. Moreover, the alterations in autonomic nervous system activity have been reported in both conditions: including unstable arterial blood pressure, hypothermia, episodes of sweating, constipation and others. The failure to maintain blood pressure in the erect position also could contribute to the commonly reported fatigue in these individuals. However, the cause and pathophysiology of these changes in autonomic function remain unclear. In our recent study we reported that individuals with SCI experience various chronic pain conditions following injury that are frequently both severe and refractory to the treatments (Widerström-Noga et al, 2004). Although there are many types of chronic pain after SCI, two broad categories can be distinguished, i.e., nociceptive and neuropathic pain. The neuropathic pains may be generated by abnormal hyperactivity of spinal neurons involved in pain transmission (Krassioukov, et al, 2002), or by decreased endogenous pain inhibitory function (Pertovaara et al, 1997). Experimental studies strongly suggest that nociceptive input to the spinal cord may play an important role in the development of autonomic dysfunctions following injury (Krassioukov, et al, 2002). For example, activity in spinal interneurons, sympathetic nerve visceral stimuli, was exaggerated in chronic spinal rats. It has been suggested that sprouting of fibres containing calcitonin gene-related peptide may be important for evoking exaggerated spinal sympathetic reflexes (Christensen and Hulsebosch, 1997; Krenz, et al, 1999; Krassioukov, et al, 2002). To our knowledge, there is no data available concerning the relationship between clinical characteristics of chronic pain and the presence of autonomic dysfunctions in humans with cervical SCI. Since painful stimuli can evoke different autonomic responses, our preliminary study was aimed to define the relationship between autonomic control and the clinical characteristics of chronic pain in persons with cervical SCI. Our findings suggest that plastic changes within the central nervous system contribute to exaggerated autonomic responses commonly observed in individuals with chronic pain. (Supported by Christopher Reeve Paralysis Foundation, Heart and Stroke Foundation of Canada, British Columbia Neurotrauma Fund.)
MIGHT GLIA BE THE CULPRIT CAUSING FIBROMYALGIA PAIN?
In chronic pain conditions, such as fibromyalgia, the assumption that is classically made is that neurons cause the problem. That is, the uncontrolled pain must be due to malfunctioning neurons in the pain pathway. I will offer a radically different view. That is, that non-neuronal cell types called glia may be the root of the problem. Spinal cord glia (astrocytes and microglia) are immune-like cells which release an array of neuroexcitatory substances when these cells are triggered to activate. Key among these spinally-released substances are the proinflammatory cytokines: interleukin-1 (IL1), interleukin-6 (IL6) and tumor necrosis factor (TNF). Evidence accruing across multiple laboratories over the past decade provide compelling support that activated glia, and their proinflammatory cytokine products, are key players in the creation and maintenance of diverse pathological pain states. This profile suggests novel approaches to pain control where spinal cord glia and their proinflammatory cytokines are the therapeutic target, rather than neurons. In animal models, this strategy is clearly successful. A novel non-viral gene therapy approach (which constrains glial activation by driving the spinal production of the anti-inflammatory cytokine interleukin-10 [IL-10]), abolishes neuropathic pain for well over 3 months. Indeed, once pain eventually returns, complete pain relief is again readily re-instated by simple follow-up IL-10 therapy. While such an approach will hopefully reach clinical trials, it is clear that pharmaceutical companies are resistant to fibromyalgia as a target population, as there are no animal models to document whether spinal glial activation does or does not occur in this syndrome. A new human postmortem project will be described which aims to provide this missing key; that is, to define whether glial activation does indeed occur in spinal cords of fibromyalgia patients compared to pain-free controls. By registering donors for this ambitious program prior to death, thorough documentation of medical, drug, and pain histories will be available in addition to anatomical, mRNA and protein analyses of spinal tissues. It will be through such a program that the role of glia in fibromyalgia pain will begin to be clarified
Dr. Burns is currently Director of Preclinical Research at Pain Therapeutics, Inc., a small biopharmaceutical company in South San Francisco devoted to developing novel drugs for severe chronic pain, such as the pain associated with osteoarthritis, low-back pain, or irritable bowel syndrome. Since joining the company in 2002, Dr. Burns and her academic collaborators have produced preclinical data that further characterizes Pain Therapeutics’ proprietary combinations of opioid agonists with ultra-low-dose opioid antagonists, elucidating the mechanism of action in enhancing analgesia and attenuating tolerance and withdrawal, as well as demonstrating their decreased potential for addiction. Dr. Lindsay Burns received her PhD in neuropsychology at the University of Cambridge, U.K., where she studied the interaction of limbic structures and dopamine in reward processing. Her post-doctoral training at McLean Hospital in Boston focused on therapies for Parkinson’s and Huntington’s diseases.
Oxytrex is a novel drug that combines oxycodone, an opiate, with ultra-low-dose naltrexone, an opioid antagonist. Pain Therapeutics, Inc. is currently conducting in Phase III clinical trials with Oxytrex in patients with low-back pain and osteoarthritis. A Phase II clinical trial in osteoarthritis demonstrated a significantly greater reduction in pain intensity by Oxytrex and prolonged pain relief compared to the equivalent dose of oxycodone alone. Extensive preclinical data has demonstrated that ultra-low-dose opioid antagonists in combination with opiates enhance analgesia, prevent tolerance, reverse established tolerance and prevent withdrawal signs. The mechanism of action of ultra-low-dose opioid antagonists is to prevent a switch in G protein coupling by opioid receptors that occurs in opioid tolerance. Both this mechanism of tolerance and its attenuation by an ultra-low-dose opioid antagonist were recently demonstrated at the molecular level. Early results in a rat neuropathic pain model demonstrate a strong and prolonged anti-hyperalgesic effect by ultra-low-dose naltrexone combined with an opiate. Rat studies have also demonstrated that ultra-low-dose opioid antagonists block the rewarding effects of acute administration of analgesic doses of morphine or oxycodone as well as the aversive effect of withdrawal after chronic administration. To further assess the addictive potential of Oxytrex compared to oxycodone alone, a rat self-administration paradigm was used. In this model, ultra-low-dose naltrexone attenuated the potency of oxycodone in self-administration and reduced relapse responding or “drug-seeking” after abstinence. Together, these preclinical and clinical results suggest that Oxytrex may have an improved therapeutic index by enhancing analgesic potency while attenuating tolerance, withdrawal and the potential for addiction
Dr. Kula 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
Pain in fibromyalgia is considered to result from a heightened central sensitization to pain. This is in essence a characterization of neuropathic pain. Two conditions - Chiari I malformations and syringomyelia, are frequently associated with neuropathic musculoskeletal pain and patients affected with these disorders are often misdiagnosed as having fibromyalgia. They are easily recognized with appropriate studies, but are extremely rare conditions. Fibromyalgia, on the other hand, is much less well understood, but considerably more common. Both types of conditions can manifest a very chronic history, onset associated with physical trauma events, and tender points on examination with a general absence of neurological findings. Although these conditions account for an expectedly low percentage of all fibromyalgia patients (< 5%), they are treatable and therefore important to recognize. Understanding the general clinical features of Chiari I malformations and syringomyelia and the importance of appropriate imaging studies will help achieve better differential diagnosis of fibromyalgia and improve patient care
Dr. Russell 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 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, and The Best 2000 Doctors in America. 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 85 original publications, over 30 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 and France. 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.
Medical care for the fibromyalgia syndrome [FMS] must be multidimensional, multimodal, and multidisciplinary. It begins with the patient selecting a physician in which he or she can be confident. The physician then should initiate the main components of a FMS management program including: diagnosis, education, exercise, and medication. If any of these is missing from the program, the outcome will be less than ideal. A new concept for the interaction between physician and patient is “shared decision making.” It is proposed that involvement of the patient at all levels provides access to improved self-efficacy, self-reliance, and benefit. Education is the physician’s responsibility but that role can be shared by paramedical professionals, peer groups, and published works that the patient can read. Physical modilities can include formal professionally-administered interventions and informal home therapies. Medication therapy should be directed as specifically as possible at the clinically symptomatic manifestation, such as pain, insomnia, fatigue, dysautonomia, irritable bowel syndrome, irritable bladder. For example, the pain may be responsive to simple analgesics in some patients, but most need the benefits offered by an increasingly sophisticated analgesic armamentarium. The newer analgesic medications have been developed in response to new information about mechanisms of chronic allodynic pain. For example, tramadol binds weakly to the mu opioid receptor, but more importantly, it increases the availability of both serotonin [5HT] and norepinephrine [NEP]. The spinal fluid [CSF] concentrations of the metabolites of these natural pain inhibitors are known to be low in people with FMS. New agents under study for FMS include an SNRI [duloxetine] and an NSRI [milnaciprin]. A 5HT3 specific receptor antagonist called tropisetron is showing benefit in FMS. Two drugs [clonidine, tizanidine] work as alpha-2-adrenergic agonists. Substance P is elevated in FMS CSF and tizanidine was shown to decrease it but monotherapy with inhibitors of the NK1 substance P receptor do not decrease pain. NMDA receptor antagonists [ketamine and dextromethorphan] exhibit efficacy in a subgroup of FMS. Anticonvulsant medications are known to raise the depolarization threshold on central nervous system neurons and gabapentin can be given with tramadol. A future member [pregabalin] in this class is under study for FMS. Parenteral human growth hormone [HGH] is useful in the therapy of FMS but currently is quite expensive and requires expensive follow-up. The cost of the drug may come down with time. Alternatively, pyridistigmine, given before exercise, may provide an alternative endogeneous source of HGH. For each of the other symptom complexes [insomnia, fatigue, dysautonomia, irritable bowel syndrome, irritable bladder], similar discussions of available medication remedies will be provided.
Dr. McCarberg is founder of the Chronic Pain Management Program for Kaiser Permanente in San Diego, California. He was on the board of directors of the American Pain Society. He is co-president of the Western Pain Society and Assistant Clinical Professor (voluntary) at the University of California at San Diego School of Medicine. Dr. McCarberg is a member of the American Academy of Family Physicians, the American Academy of Pain Medicine, the American Pain Society, and the International Association for the Study of Pain. He is the recipient of several awards, including the Shilling Compassionate Care Award, and in 1998 was named the Highest Rated Physician by Member Appraisal of Physician Services at Kaiser Permanente. He also received the Elizabeth Narcessian award for leader in the field of pain education from the American Pain Society. He has given more than 100 presentations on pain management issues and is the author or co-author of several publications. He is board certified by the American College of Pain Medicine, the American Board of Family Practice and additionally certified in Geriatrics. Dr. McCarberg received his MD degree from Northwestern University Medical School in Chicago, Illinois. He completed a medical internship and a residency in family practice at Highland Hospital in Rochester, New York.
Pain is the most common reason patients consult primary care providers. A recent poll concluded that tension headache, menstrual pain, low back pain, muscle pain, and neck pain were responsible for 50 million sick days per year in the United States at an annual cost of more than $3 billion. Pain negatively affects quality of life including spiritual, social, and psychological well being. One study reported that 42% of pain sufferers believed that pain affected their personal and work relationships, 35% reported missing more than 20 days of work per years, 28% believed their pain had impaired th4eir job performance, and 70% continued to experience pain despite tre4atments. Numerous reports describe the under-treatment of pain even in terminal cancer. The plight of the patient with chronic non-cancer pain is even worse. This deplorable stat of pai care has led to numerous initiatives including pain standards mandated by the Joint Commission on Accreditation of Healthcare Organizations and the declaration by Congress of the Decade of Pain Control and Research. Pain specialists and organizations supporting the work of these clinicians have done land-breaking work to improve pain management in America. However, the health care provider who has the greatest potential to impact a patient’s pain and suffering remains marginalized in this process – the primary care provider. There are many reasons for the inadequacy of this group of practitioners. The presenter, who is a family physician and a pain clinician, will offer insight into the problem. It remains an undeniable fact, if our primary care community does not address pain management, the problem with under-treated pain and suffering will continue despite initiatives, declarations by Congress, pain clinics and well conceived clinical practice guidelines. The primary care provider is vital in the caring for chronic pain patients; without this group of overworked, underappreciated clinicians, pain will continue for the foreseeable future as it has for many past decades.
The pain and absenteeism report, employees; employee benefits manager. New ork:Ortho-McNeil Pharmaceutical/Louis Harris and Associates, 1996. DeShano CL. Michigan moves toward better pain management. Mich Med 1997; 96(1):16-21.
Dr. Jones is an Assistant Professor at the Oregon Health and Science University School of Nursing. 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 or Graduate Teaching Assistant, Primary Health Care Nurse Practitioner Programs at Oregon Health and Science University School of Nursing. In addition, she is the Medical Director of the Oregon Health and Science University Health Systems Management, Nurse Practitioner, Rheumatology Clinic. Prior to her tenure at OHSU she was an Assistant Professor at Georgia State University in the Family Nurse Practitioner Program. Dr. Jones’ most current published papers include work with Dr. Robert Bennett’s fibromyalgia group at OHSU. Recently they were awarded an NIH grant to study pyridostigmine bromide and exercise in FM patients. The GH stimulating effect of this drug is impressive and far more cost effective than growth hormone.
Dr. Jones will present her work, as well as that of the Oregon Health and Science University fibromyalgia research team. Her expertise is in the growth hormone/insulin like growth factor axis in fibromyalgia. She specializes in how to maximize symptom management through drug and exercise interventions. Dr. Jones’ postulates that muscle pain and fatigue in fibromyalgia are amplified in part due to dysfunctions in the GH/IGF-1 axis. Furthermore, she will suggest treatments to optimize function in fibromyalgia. Her presentation will include theoretical considerations, preliminary research findings and clinical experience with growth hormone manipulating medications.
Dr. Jasmin is currently involved in a clinical practice centered on the treatment of pain and spinal disorders. He and his colleagues are conducting basic research on pain mechanisms and gene therapy for pain as well as on Schwann cell remyelination of the spinal cord. 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-three 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. His accomplishments also include a 2002 patent 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.
Many individuals with generalized or regional pain syndromes have abnormal hypothalamic responses to stress, but a precise relationship between the pain syndrome and a dysfunction of the hypothalamo-pituitary-adrenal (HPA) axis remains elusive. We and others have postulated that a blunted hypothalamic response to stress might lead to decreased nociceptive thresholds. To test this hypothesis we measured the nociceptive responses in two genetically distinct inbred strains of rats, Lewis and Fischer. The hypothalamus of Lewis rats is hyporesponsive compared to that of Fischer rats. When submitted to inflammatory or anxiogenic stimuli, Lewis rats have a blunted HPA axis response as measured by adrenocorticotropic hormone (ACTH) and corticosterone release. Lewis rats, however, have lower nociceptive thresholds in withdrawal responses to both heat and paw pinch stimuli, but showed less stress behavior. In both Lewis and Fisher rats, intracerebroventricular injection of corticotropin-releasing factor (CRF) has a dose-dependent antinociceptive effect while astressin (a non-selective antagonist for both CRF receptor 1 and 2) has a dose-dependent hyperalgesic effect. Contrary to their effect on pain, CRF increased and astressin decreased the stress responses. Compared to Fischer rats, Lewis rats have a greater response to CRF as shown by a lower effective dose but a reduced response to astressin. From this data, we suggest that while hypothalamic dysfunction results in altered nociceptive thresholds and stress responses, both phenomena might be independent from each other.
Dr. Larson is a Professor of Pharmacology and Neuroscience at the University of Minnesota. She received her PhD in Pharmacology at the University of Minnesota School of Medicine in 1977. She did postdoctoral work in the area of electrophysiology at the University of Illinois and returned to the University of Minnesota where she has taught and done research on the mechanisms underlying pain transmission for the past 25 years.
Nerve growth factor (NGF) is a substance that is essential for the survival of sympathetic as well as sensory neurons. It is produced during development and in situations involving injury and inflammation. Throughout life NGF promotes tissue repair and discourages use of the afflicted region by enhancing pain and hypersensitivity to touch. While this is normally self-limiting, in some situations of chronic widespread pain the production of NGF appears to be persistent. We have found that NGF is increased four-fold in the cerebrospinal fluid of people with FMS compared to that in healthy normal controls. This increase is restricted to patients who have primary fibromyalgia (PFMS), i.e. FMS without any other inflammatory conditions such as lupus or rheumatoid arthritis. People who had secondary fibromyalgia (SFMS), i.e. FMS together with other painful disorders, or who had regional pain (RP), such as low back pain and very painful arthritis, did not have significantly elevated NGF in their spinal fluid. Thus, elevated concentrations of NGF in this area appear to be unique to this PFMS group. Because the concentration of NGF is normally negligible in healthy normal people, the origin of this growth factor in patients with PFMS is unclear. Our goal is to determine the source of this compound and factors that regulate its synthesis in the CNS.
Dr. Wood 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.
Dr. Wood will present his model of Fibromyalgia Syndrome, which postulates that enhanced activity of hippocampal NMDA glutamate receptors exerts a pathological inhibition of dopamine release within brain centers critical to both pain perception and a variety of comorbid symptoms associated with the disorder. His presentation will include theoretical considerations, preliminary research findings and clinical experience with dopaminergic medications.
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