Fibromyalgia: California

Abad VC, Sarinas PS, Guilleminault C. · Clinical Monitoring Sleep Disorders Center, Camino Medical Group, Palo Alto Medical Foundation, USA. · Sleep Med Rev. · Pubmed #18486034 No free full text.

Abstract: Arthritis is the leading cause of chronic illness in the United States. Seventy-two percent of the adults aged 55 years and older with arthritis report sleep difficulties. This review discusses sleep disorders associated with rheumatoid arthritis, juvenile rheumatoid arthritis, Sjogren's syndrome, systemic lupus erythematosus, scleroderma, Behcet's disease, seronegative spondyloarthropathies, osteoarthritis, sarcoidosis, and fibromyalgia. We describe the inter-relationship between sleep complaints, disease activity, depression, sleep deprivation, and cytokines. An algorithm for evaluation and treatment of sleep disorders associated with rheumatologic diseases is proposed.

Clark GT. · Department of Diagnostic Sciences, University of Southern California, School of Dentistry, 925 West 34th Street, Los Angeles, CA 90089-0641, USA. · Oral Maxillofac Surg Clin North Am. · Pubmed #18343321 No free full text.

Abstract: This article focuses on chronic myogenous pains affecting the masticatory muscles, including focal myalgia, regional myalgia, myofascial pain, and fibromyalgia. The probable mechanisms are discussed and treatment options, including self-directed treatment, physical medicine modalities, and several types of pharmacologic agents, are presented.

McDermott BE, Feldman MD. · University of California, Davis School of Medicine, Department of Psychiatry and Behavioral Sciences, Division of Psychiatry and the Law, 2230 Stockton Blvd, 2nd Floor, Sacramento, CA 95817, USA. · Psychiatr Clin North Am. · Pubmed #17938038 No free full text.

Abstract: Malingering of mental illness has been studied extensively; however, malingered medical illness has been examined much less avidly. While in theory any ailment can be fabricated or self-induced, pain--including lower back pain, cervical pain, and fibromyalgia--and cognitive deficits associated with mild head trauma or toxic exposure are feigned most frequently, especially in situations where there are financial incentives to malinger. Structured assessments have been developed to help detect both types of malingering; however, in daily practice, the physician should generally suspect malingering when there are tangible incentives and when reported symptoms do not match the physical examination or no organic basis for the physical complaints is found.

Wallace DJ, Gotto J. · Cedars-Sinai Medical Center, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA. · Semin Arthritis Rheum. · Pubmed #17570468 No free full text.

Abstract: OBJECTIVE: To present a hypothesis accounting for the differential response of bipolar patients diagnosed with fibromyalgia (FM) to standard therapies, taking into account the markedly statistically significant increase of its prevalence in the syndrome. METHODS: All articles relating to the heading bipolar illness AND fibromyalgia as well as bipolar illness AND pain were searched using PubMed and Medline since 1966. The prevalence of bipolar illness in our last 100 FM consultations was reviewed. RESULTS: Ten percent of our 100 most recent FM consultations included patients with an established diagnosis of bipolar illness. They had little if no response to traditional FM interventions and appeared to have vague and uncertain tender point examinations. CONCLUSIONS: Bipolar illness may be associated with a form of chronic musculoskeletal pain complaints that is not FM. Studies into the role that neurotransmitters play in bipolar patients with complaints of musculoskeletal discomfort deserve further exploration.

Pardi D, Black J. · Jazz Pharmaceuticals Inc, Palo Alto, CA, USA. · CNS Drugs. · Pubmed #17140279 No free full text.

Abstract: gamma-Hydroxybutyrate (GHB) is an endogenous short chain fatty acid and a, mostly oral, pharmacological compound that has been utilised in a variety of ways. Endogenously, GHB is synthesised locally within the CNS, mostly from its parent compound GABA. Sodium oxybate is the sodium salt of GHB and is used for the exogenous oral administration of GHB. It is likely that supraphysiological concentrations of GHB from exogenous administration produce qualitatively different neuronal actions than those produced by endogenous GHB concentrations.Evidence suggests a role for GHB as a neuromodulator/neurotransmitter. Under endogenous conditions and concentrations, and depending on the cell group affected, GHB may increase or decrease neuronal activity by inhibiting the release of neurotransmitters that are co-localised with GHB. After exogenous administration, most of the observed behavioural effects appear to be mediated via the activity of GHB at GABA(B) receptors, as long as the concentration is sufficient to elicit binding, which does not happen at endogenous concentrations. Endogenous and exogenous GHB is rapidly and completely converted into CO(2) and H(2)O through the tricarboxylic acid cycle (Krebs cycle). Sodium oxybate has been observed to modulate sleep in nonclinical study participants, and sleep and wakefulness in clinical populations, including groups with insomnia, fibromyalgia and narcolepsy. In narcolepsy, sodium oxybate has shown dose-related effects on various properties of sleep, including increases in slow-wave sleep duration and delta power, and a reduced number of night-time awakenings. Furthermore, multiple measures of daytime sleepiness and cataplexy demonstrated consistent short- and long-term improvement in response to night-time sodium oxybate therapy. The most common reported adverse events include dose-related headache, nausea, dizziness and somnolence.

Wallace DJ. · Cedars-Sinai/David Geffen School of Medicine at UCLA, Los Angeles, CA, USA. · Curr Pharm Des. · Pubmed #16454720 No free full text.

Abstract: Cytokines are glycoproteins that serve as chemical messengers between cells. They assist in the regulation of cell growth and repair and also have immune modulating properties. Cytokines play a role in diverse clinical processes and phenomena such as fatigue, fever, sleep, pain, stress and aching. A review of the fibromyalgia literature and related studies suggest that IL-1, IL-6 and IL-8 are dysregulated in the syndrome. Therapies directed against these cytokines may be of potential importance in the management of fibromyalgia.

Krell HV, Leuchter AF, Cook IA, Abrams M. · Laboratory of Behavioral Pharmacology, UCLA Neuropsychiatric Institute, 37-452 NPI, 760 Westwood Plaza, Los Angeles, CA 90024, USA. · Psychosomatics. · Pubmed #16145181 links to  free full text

Abstract: Clinical experience supports the use of antidepressant medications to treat chronic pain syndromes, such as low back pain and fibromyalgia. Although this use of antidepressants is common in clinical practice, the literature supporting this off-label use has some limitations. In this report, the authors review the body of clinical data on the use of antidepressants in treating pain and present a case series of depressed patients with these syndromes who experienced relief of pain symptoms while being treated with the noradrenergic antidepressant reboxetine. These subjects experienced significant relief of pain before any significant improvement in actual mood symptoms. Our experience with reboxetine suggests that this noradrenergic antidepressant may have efficacy in the treatment of chronic pain in patients with depression.

Rowbotham MC. · University of California San Francisco Pain Clinical Research Center, San Francisco, California 94115, USA. · J Rheumatol Suppl. · Pubmed #16078359 No free full text.

Abstract: The fibromyalgia syndrome (FM) seems an unlikely candidate for classification as a neuropathic pain. The disorder is diagnosed based on a compatible history and the presence of multiple areas of musculoskeletal tenderness. A consistent pathology in either the peripheral or central nervous system (CNS) has not been demonstrated in patients with FM, and they are not at higher risk for diseases of the CNS such as multiple sclerosis or of the peripheral nervous system such as peripheral neuropathy. A large proportion of FM sufferers have accompanying symptoms and signs of uncertain etiology, such as chronic fatigue, sleep disturbance, and bowel/bladder irritability. With the exception of migraine headaches and possibly irritable bowel syndrome, the accompanying disorders are clearly not neurological in origin. The impetus to classify the FM as a neuropathic pain comes from multiple lines of research suggesting widespread pain and tenderness are associated with chronic sensitization of the CNS. An examination of how the term neuropathic pain is defined reveals a conceptual split into 2 partially overlapping groups of disorders: those with demonstrable pathology in the nervous system and those characterized primarily by enduring dysfunction in the nervous system. Requiring demonstrable pathology in the nervous system in the definition of neuropathic pain is the traditional approach. The expansion of the definition to require only enduring nervous system dysfunction is less palatable because it opens the classification to many disorders of uncertain etiology, including complex regional pain syndrome. As it is uncertain which of the many different chronic pain syndromes include an enduring component of central sensitization, restricting the term "neuropathic pain" to those disorders with a primary etiology clearly related to the peripheral or CNS is prudent and consistent with clinical practice.

Levine JD, Reichling DB. · Division of Rheumatology, Department of Medicine, University of California, San Francisco, California 94143-0440, USA. · J Rheumatol Suppl. · Pubmed #16078358 No free full text.

Abstract: Fibromyalgia syndrome (FM) is a common, often debilitating and intractable, chronic, generalized pain condition. The development of effective therapies to treat FM has been hindered by a lack of understanding of fundamental mechanisms in the etiology of FM. In view of prominent characteristics that FM shares with other generalized pain conditions, we suggest that a key mechanism in such disorders may be that of altered activity in the subdiaphragmatic vagus nerve. Specifically, we propose that activity in vagal afferents, arising from the gastrointestinal tract, and sympathoadrenal function mediate a contribution of stress to FM and its strong association with irritable bowel syndrome. An important prediction of the proposed mechanism is that interventions that selectively modulate activity in specific populations of subdiaphragmatic afferents might be used to treat the symptoms of FM and other generalized pain syndromes.

DiNucci EM. · Stanford University, Stanford, CA, USA. · Orthop Nurs. · Pubmed #16056170 No free full text.

Abstract: Complementary and alternative therapies continue to grow in popularity among healthcare consumers. Among those modalities is energy healing (EH) (Eisenberg et al., 1998). EH is an adjunctive treatment that is noninvasive and poses little downside risk to patients. Well more than 50 major hospitals and clinics throughout the United States offer EH to patients (DiNucci, research table on healthcare facilities that offer Reiki, unpublished data, 2002). The National Institutes of Health is funding numerous EH studies that are examining its effects on a variety of conditions, including temporomandibular joint disorders, wrist fractures, cardiovascular health, cancer, wound healing, neonatal stress, pain, fibromyalgia, and AIDS (National Institutes of Health, 2004a). Several well-designed studies to date show significant outcomes for such conditions as wound healing (Grad, 1965) and advanced AIDS (Sicher, Targ, Moore, & Smith, 1998), and positive results for pain and anxiety (Aetna IntelliHealth, 2003a; Wardell, Weymouth, 2004), among others (Gallob, 2003). It is also suggested that EH may have positive effects on various orthopaedic conditions, including fracture healing, arthritis, and muscle and connective tissue (Prestwood, 2003). Because negative outcomes risk is at or near zero throughout the literature, EH is a candidate for use on many medical conditions.

Fox RI. · Rheumatology Clinic, Scripps Memorial Hospital and Research Foundation, La Jolla, CA 92037, USA. · Lancet. · Pubmed #16039337 No free full text.

Abstract: Sjögren's syndrome is a chronic autoimmune disorder of the exocrine glands with associated lymphocytic infiltrates of the affected glands. Dryness of the mouth and eyes results from involvement of the salivary and lacrimal glands. The accessibility of these glands to biopsy enables study of the molecular biology of a tissue-specific autoimmune process. The exocrinopathy can be encountered alone (primary Sjögren's syndrome) or in the presence of another autoimmune disorder such as rheumatoid arthritis, systemic lupus erythematosus, or progressive systemic sclerosis. A new international consensus for diagnosis requires objective signs and symptoms of dryness including a characteristic appearance of a biopsy sample from a minor salivary gland or autoantibody such as anti-SS-A. Exclusions to the diagnosis include infections with HIV, human T-lymphotropic virus type I, or hepatitis C virus. Therapy includes topical agents to improve moisture and decrease inflammation. Systemic therapy includes steroidal and non-steroidal anti-inflammatory agents, disease-modifying agents, and cytotoxic agents to address the extraglandular manifestations involving skin, lung, heart, kidneys, and nervous system (peripheral and central) and haematological and lymphoproliferative disorders. The most difficult challenge in diagnosis and therapy is patients with symptoms of fibromyalgia (arthralgia, myalgia, fatigue) and oral and ocular dryness in the presence of circulating antinuclear antibodies.

Clark GT, Minakuchi H, Lotaif AC. · Division of Diagnostic Sciences, University of Southern California, School of Dentistry, 925 West 34th Street, Room B-14, Los Angeles, CA 90089-0641, USA. · Dent Clin North Am. · Pubmed #15755409 No free full text.

Abstract: Many orofacial pain conditions occur in the elderly. Specifically,this article reviews the prevalence of general and orofacial-related pain in the elderly. The authors also describe and discuss the likely disorders and diseases that produce facial pain and burning pain in the mouth. They do not cover jaw joint pain, oral sores, or ulceration-induced pain, as these conditions are better discussed in the context of arthritis and oral pathologies of the mouth. The authors discuss oral motor disorders, myogenous pain, vascular pain, headaches, trigeminal neuralgia, trigeminal neuropathic dis-ease, postherpetic neuralgia, burning mouth syndrome, and occlusal dysesthesia.

Maizels M, McCarberg B. · Department of Family Practice, Kaiser Permanente, Woodland Hills, California 91365, USA. · Am Fam Physician. · Pubmed #15712623 links to  free full text

Abstract: The development of newer classes of antidepressants and second-generation antiepileptic drugs has created unprecedented opportunities for the treatment of chronic pain. These drugs modulate pain transmission by interacting with specific neurotransmitters and ion channels. The actions of antidepressants and antiepileptic drugs differ in neuropathic and non-neuropathic pain, and agents within each medication class have varying degrees of efficacy. Tricyclic antidepressants (e.g., amitriptyline, nortriptyline, desipramine) and certain novel antidepressants (i.e., bupropion, venlafaxine, duloxetine) are effective in the treatment of neuropathic pain. The analgesic effect of these drugs is independent of their antidepressant effect and appears strongest in agents with mixed-receptor or predominantly noradrenergic activity, rather than serotoninergic activity. First-generation antiepileptic drugs (i.e., carbamazepine, phenytoin) and second-generation antiepileptic drugs (e.g., gabapentin, pregabalin) are effective in the treatment of neuropathic pain. The efficacy of antidepressants and antiepileptic drugs in the treatment of neuropathic pain is comparable; tolerability also is comparable, but safety and side effect profiles differ. Tricyclic antidepressants are the most cost-effective agents, but second-generation antiepileptic drugs are associated with fewer safety concerns in elderly patients. Tricyclic antidepressants have documented (although limited) efficacy in the treatment of fibromyalgia and chronic low back pain. Recent evidence suggests that duloxetine and pregabalin have modest efficacy in patients with fibromyalgia.

Wallace DJ, Hallegua DS. · Cedars-Sinai/UCLA School of Medicine, 8737 Beverly Blvd., Suite 203, Los Angeles, CA 90048, USA. · Curr Pain Headache Rep. · Pubmed #15361320 No free full text.

Abstract: Patients with fibromyalgia (FM) frequently have gastrointestinal symptoms and signs. This article critically reviews the available literature and concludes the following: evidence that inflammatory bowel disease is associated with FM is contradictory, but should be looked for in patients taking concomitant steroids; patients diagnosed with celiac disease often have a history of FM or irritable bowel syndrome (IBS) that may or may not be present; reflux, nonulcer dyspepsia, and noncardiac chest pain are common in FM patients; medications used to manage pain, inflammation, and gastrointestinal complaints confound the management of FM; and IBS affects smooth muscles and the parasympathetic nervous system, while FM patients have complaints of striated muscles and dysfunction of the sympathetic nervous system. Of those patients with FM, 30% to 70% have concurrent IBS. Small intestinal bacterial overgrowth is associated with hyperalgesia and IBS-like complaints, is common in FM, and responds transiently to antimicrobial therapy.

Rao SG, Clauw DJ. · Cypress Bioscience, San Diego, California 92121, USA. · Drugs Today (Barc). · Pubmed #15349132 No free full text.

Abstract: Fibromyalgia is one of a number of overlapping "functional somatic syndromes", including irritable bowel syndrome, tension headache, chronic idiopathic lower back pain, chronic fatigue syndrome and others. These conditions affect females more frequently than males and probably share common underlying neurobiological mechanisms, as well as frequent psychological, cognitive and behavioral comorbidities. Since the pain in these conditions is most likely "central" in origin, classes of drugs such as nonsteroidal antiinflammatory drugs (NSAIDs) and opioids, which are quite effective for "peripheral" pain, are relatively ineffective for the pain seen in these syndromes. Instead, tricyclic and other classes of antidepressants, antiseizure drugs and a number of other neuroactive compounds seem to be more effective. In addition, nonpharmacological therapies such as aerobic exercise and cognitive behavioral therapy are quite effective and frequently underutilized in clinical practice.

Lin HC. · Division of Gastrointestinal and Liver Diseases, Department of Medicine, Keck School of Medicine, University of Southern California, Los Angeles 90033, USA. · JAMA. · Pubmed #15316000 links to  free full text

Abstract: CONTEXT: Irritable bowel syndrome (IBS), which affects 11% to 14% of the population, is a puzzling condition with multiple models of pathophysiology including altered motility, visceral hypersensitivity, abnormal brain-gut interaction, autonomic dysfunction, and immune activation. Although no conceptual framework accounts for all the symptoms and observations in IBS, a unifying explanation may exist since 92% of these patients share the symptom of bloating regardless of their predominant complaint. EVIDENCE ACQUISITION: Ovid MEDLINE was searched through May 2004 for relevant English-language articles beginning with those related to bloating, gas, and IBS. Bibliographies of pertinent articles and books were also scanned for additional suitable citations. EVIDENCE SYNTHESIS: The possibility that small intestinal bacterial overgrowth (SIBO) may explain bloating in IBS is supported by greater total hydrogen excretion after lactulose ingestion, a correlation between the pattern of bowel movement and the type of excreted gas, a prevalence of abnormal lactulose breath test in 84% of IBS patients, and a 75% improvement of IBS symptoms after eradication of SIBO. Altered gastrointestinal motility and sensation, changed activity of the central nervous system, and increased sympathetic drive and immune activation may be understood as consequences of the host response to SIBO. CONCLUSIONS: The gastrointestinal and immune effects of SIBO provide a possible unifying framework for understanding frequent observations in IBS, including postprandial bloating and distension, altered motility, visceral hypersensitivity, abnormal brain-gut interaction, autonomic dysfunction, and immune activation.

Shuer ML. · Mood & Menopause Clinic, P.O. Box 462223, Escondido, CA 92046-2223, USA. · Endocrine. · Pubmed #14610300 No free full text.

Abstract: Fibromyalgia (FM) is a disease entity consisting of a heterogeneous cluster of symptoms that has thus far eluded identification of a causative etiology. The disease onset appears to follow physiological and/or psychological stressors and involves a subset of symptoms that are consistent with varied disorders found in multiple medical specialties to include rheumatology, immunology, endocrinology, neurology, and psychiatry. Owing to the heterogeneity of the symptom complex and the heretofore absence of serum markers that might serve as concrete diagnostic criteria, this disease has baffled clinicians and basic scientists alike. Recent findings regarding sleep architecture, immunology, and endocrinology have provided clues that may help in the understanding and resultant treatment of this entity. Women with fibromyalgia tend to present with an alpha-delta sleep anomaly, which when treated with a growth hormone secretagogue (GHS), reduces the rheumatological pain and restores slow-wave sleep architecture. These findings suggest the somatotrophic axis may be involved in the etiology and the treatment of this disorder. Those diagnosed with FM respond to various stressors with increased disruption of their physiological homeostasis. When compared to healthy age-matched cohorts, there are quantitative differences in various neuroactive steroid levels, immunological markers, and feedback mechanisms. The varied physiological alterations in patients diagnosed with fibromyalgia when compared to controls will be discussed along with the potential treatment options for this population.

Rao SG, Bennett RM. · Cypress Bioscience, 4350 Executive Drive, Suite 325, San Diego, CA 92121, USA. · Best Pract Res Clin Rheumatol. · Pubmed #12849715 No free full text.

Abstract: The fibromyalgia syndrome (FMS) is a common, chronic, widespread pain disorder that mainly affects middle-aged women. In addition to pain complaints, fatigue and disturbed sleep are symptoms frequently reported by these patients. Many FMS patients also meet diagnostic criteria for mood disorders (e.g. depression) as well as other so-called 'functional somatic syndromes', including irritable bowel syndrome, temporomandibular joint disorder, and subsets of chronic low-back pain. A wide variety of medications are used to manage the eclectic symptomatology of FMS patients, although relatively few have been rigorously tested. This chapter provides a contemporary update of the state of FMS pharmacotherapy, with an emphasis on compounds that have been tested in double-blind, randomized, controlled trials. Particular attention is paid to the efficacy of these therapies on the associated symptoms and co-morbid syndromes commonly seen in FMS patients.

Sheean G. · EMG and Neuromuscular Service, University of California, San Diego, 200 West Arbor Drive, San Diego 92103-8465, USA. · Curr Pain Headache Rep. · Pubmed #12413405 No free full text.

Abstract: The impressive pain relief experienced by sufferers of dystonia and spasticity from intramuscular injections of botulinum toxin suggested that patients with other chronic, musculoskeletal pain conditions also may benefit. However, there have been relatively few placebo-controlled studies of botulinum toxin in such non-neurologic conditions as myofascial pain syndrome, chronic neck and low back pain, and fibromyalgia; the results of these studies have not been impressive. One explanation for the lack of positive findings may be the lack of clinically evident muscle spasms (overactivity), despite the presence of muscle tenderness, tightness, or trigger points. Clinical observations of pain relief from injections of botulinum toxin for dystonia and spasticity and its apparent efficacy in treating migraine suggest an anti-nociceptive action independent of its neuromuscular junction-blocking action. Evidence from animal experiments supports this notion, and other data provide plausible physiologic mechanisms in the periphery and central nervous systems. These involve modulation of the activity of the neurotransmitters glutamate, substance P, calcitonin gene-related peptide, enkephalins, and others. However, even if botulinum toxin is firmly established as an analgesic, there is insufficient clinical evidence of its efficacy in treating non-neurologic, chronic, musculoskeletal pain conditions.

Kranzler JD, Gendreau JF, Rao SG. · Cypress Bioscience, Inc., 4350 Executive Drive, Suite 325, San Diego, CA 92121, USA. · Psychopharmacol Bull. · Pubmed #12397854 links to  free full text

Abstract: The fibromyalgia syndrome (FMS) is the most frequent cause of chronic widespread pain. In this review, we summarize the state of the art on the syndrome and its pathophysiology, with an emphasis on identifying bases for the development of novel therapies. Toward this end, the anatomy and physiology of pain pathways are summarized, followed by a review of the altered biology of pain processing, neurotransmitter function, and neuroendocrine systems in FMS. The categories of drugs currently employed to treat the disorder are detailed, along with a critical review of the literature supporting such use. Throughout the article, FMS is compared with and related to both major depressive disorder and neuropathic pain, conditions that may share some common biological processes with FMS but for which new drug discovery efforts are significantly more active due to the more established nature of these diagnoses.

Silver DS, Wallace DJ. · Division of Rheumatology, Cedars-Sinai Medical Center, UCLA School of Medicine, Los Angeles, CA 90048, USA. · Rheum Dis Clin North Am. · Pubmed #12122927 No free full text.

Abstract: Most of the six million Americans with fibromyalgia have at least one associated syndrome which mandates specialized attention in addition to traditional therapeutic approaches. These include localized procedures, regional blocks, antiinflammatory or antimicrobial regimens, attention to non soft tissue sources of psychosocial distress, and classes of medicines not usually prescribed for fibromyalgia. The successful treatment of fibromyalgia-associated syndromes improves the symptoms, quality of life, and prognosis of fibromyalgia.

Rao SG. · Cypress Bioscience, 4350 Executive Drive, Suite 325, San Diego, CA 92131, USA. · Rheum Dis Clin North Am. · Pubmed #12122916 No free full text.

Abstract: As demonstrated above, the anatomy and neuropharmacology of the pain pathways within the CNS, even to the level of the midbrain, are extraordinarily complex. Indeed, discussions of the effects of these agents on the neuropharmacology of the thalamus, hypothalamus, and cortex were excluded from this review owing to their adding further to this complexity. Also, the dearth of data regarding FMS pain pathophysiology necessitated a relatively generic analysis of the pain pathways. As mentioned in the introduction, the current thought is that central sensitization plays an important role in FMS. However, we see in this chapter that the behavioral state of central sensitization may be a result of alterations in either the ascending systems or in one or more descending systems. Studies to assess the presence or relative importance of such changes in FMS are difficult to perform in humans, and to date there are no animal models of FMS. Accepting these limitations, it is apparent that many drugs considered to date for the treatment of FMS do target a number of appropriate sites within both the ascending and descending pain pathways. The data regarding clinical efficacy on some good candidate agents, however, is extremely preliminary. For example, it is evident from the present analysis that SNRIs, alpha 2 agonists, and NK1 antagonists may be particularly well suited to FMS, although current data supporting their use is either anecdotal or from open-label trials [114,149]. Other sites within the pain pathways have not yet been targeted. Examples of these include the use of CCKB antagonists to block on-cell activation or of nitric oxide synthetase antagonists to block the downstream mediators of NMDA activation. Efficacy of such agents may give considerable insight into the pathophysiology of FMS. Finally, as indicated previously, FMS consists of more than just chronic pain, and the question of how sleep abnormalities, depression, fatigues, and so forth tie into disordered pain processing is being researched actively. Future research focusing on how the various manifestations of FMS relate to one another undoubtedly will lead to a more rational targeting of drugs in this complex disorder.

Clyman B. · VA Greater Los Angeles Health Care System, 534 Hillgreen Drive, Beverly Hills, CA 90212, USA. · Curr Rheumatol Rep. · Pubmed #11709115 No free full text.

Abstract: Few medical professionals would dispute the obvious health benefits afforded by regular exercise if pursued judiciously and in moderation. Cardiovascular disease, hypertension, osteoporosis, diabetes, depression, and fibromyalgia are a few of the many disorders in which exercise plays a key role in management. Less well-appreciated until recently is the beneficial effect exercise may have in the treatment of osteoarthritis (OA). Previously, rest and inactivity seemed to be the prevailing treatment strategy until it was recognized that this approach was ineffective and contributed further to the patient's disability and loss of function. New trial data support the value of physical exercise whether it involves aerobic or resistance-type training. The studies are not without statistical and methodologic imperfections. Still, the evidence favoring an exercise intervention as part of the OA treatment plan is impressive. It remains for the clinician to select an appropriate exercise routine that meets the strength, balance, flexibility, and aerobic needs of the patient. The clinician then monitors and evaluates the patient's response to this activity with the same exactness used in following pharmacologic therapy.

Wallace DJ, Hallegua DS. · Department of Medicine/Division of Rheumatology, Cedars-Sinai Medical Center/UCLA School of Medicine, 8737 Beverly Building, Los Angeles, CA 90048, USA. · Curr Pain Headache Rep. · Pubmed #11403734 No free full text.

Abstract: Patients with fibromyalgia have an altered quality of life that is hard to quantitate using existing indices. The principal legal issues associated with the syndrome are: Does fibromyalgia exist? Can it be caused by or flared by stress or trauma? Does disability apply to fibromyalgia and if so, how? These issues are critically reviewed.

Fox RI, Stern M, Michelson P. · Allergy and Rheumatology Clinic, Scripps Memorial Hospital and Research Foundation, La Jolla, California 92037, USA. · Curr Opin Rheumatol. · Pubmed #10990175 No free full text.

Abstract: Sjögren syndrome (SS), the second most common autoimmune rheumatic disease, refers to keratoconjunctivitis sicca and xerostomia resulting from immune lymphocytes that infiltrate the lacrimal and salivary glands. However, differential diagnosis remains confusing due to the high prevalence of vague symptoms of dryness, fatigue, and myalgias in the general population. The problems of diagnosis are further compounded by the finding of "positive" antinuclear antibodies in a high percent of the general population. Unless minor salivary gland biopsies are read by experienced observers, nonspecific changes of sialadenitis are frequently confused with the focal lymphocytic infiltrates that are characteristic of SS. The distinction between fibromyalgia patients with low titer antinuclear antibodies and primary SS remains difficult. Even in patients fulfilling strict criteria for SS, the genomic search for critical genes has proven difficult due to the multigenic pattern of inheritance and strong role of currently undefined environmental factors. No single environmental factor has been detected in the majority of SS patients. SS-like syndrome has been detected in certain patients with HTLV-1 and hepatitis C infection, providing clues to pathogenesis. Even in SS patients with marked sicca symptoms, minor salivary gland biopsy shows that almost 50% of glandular cells are still detected on biopsy. These results imply the importance of immune factors such as cytokines and autoantibodies in decreasing neuro-secretory circuits and induction of glandular dysfunction. Of potential importance, an antibody against muscarinic M3 receptor that can decrease secretory function when injected into rodents is frequently found in the sera of SS patients. Newly developed topical and oral therapies can ease the oral and ocular dryness. Orally administered agonists of the muscarinic M3 receptor (pilocarpine and cevimeline) have recently been approved by the US Food and Drug Administration to increase salivary secretion. Topical ocular use of low-dose corticosteroids or cyclosporin may decrease conjunctival surface inflammation. In a Phase II double-blind study, orally administered interferon alpha (150 U) led to improved saliva flow and symptoms. In pregnant patients with evidence of fetal distress, oral dexamethasone is preferred because this agent crosses the placenta effectively. In animal models, antagonists of tumor necrosis factor and inhibitors of de novo pyrimidine synthesis appear promising.