Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0016053 (fibromyalgia)
 4,687 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Substance P (SP), a putative nociceptive transmitter, is increased in the CSF of patients with fibromyalgia syndrome (FMS). Because excitatory amino acids (EAAs) also appear to transmit pain, we hypothesized that CSF EAAs may be similarly involved in this syndrome. We found that the mean concentrations of most amino acids in the CSF did not differ amongst groups of subjects with primary FMS (PFMS), fibromyalgia associated with other conditions (SFMS), other painful conditions not exhibiting fibromyalgia (OTHER) or age-matched, healthy normal controls (HNC). However, in SFMS patients, individual measures of pain intensity, determined using an examination-based measure of pain intensity, the tender point index (TPI), covaried with their respective concentrations of glutamine and asparagine, metabolites of glutamate and aspartate, respectively. This suggests that re-uptake and biotransformation mask pain-related increases in EAAs. Individual concentrations of glycine and taurine also correlated with their respective TPI values in patients with PFMS. While taurine is affected by a variety of excitatory manipulations, glycine is an inhibitory transmitter as well as a positive modulator of the N-methyl-D-asparate (NMDA) receptor. In both PFMS and SFMS patients, TPI covaried with arginine, the precursor to nitric oxide (NO), whose concentrations, in turn, correlated with those of citrulline, a byproduct of NO synthesis. These events predict involvement of NO, a potent signaling molecule thought to be involved in pain processing. Together these metabolic changes that covary with the intensity of pain in patients with FMS may reflect increased EAA release and a positive modulation of NMDA receptors by glycine, perhaps resulting in enhanced synthesis of NO.
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PMID:Changes in the concentrations of amino acids in the cerebrospinal fluid that correlate with pain in patients with fibromyalgia: implications for nitric oxide pathways. 1092 13

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.
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PMID:Botulinum toxin for the treatment of musculoskeletal pain and spasm. 1241 5

The common co-existence of fibromyalgia and chronic abdominal pain could be due to sensitization of spinal neurones (SNs), as a result of viscero-somatic convergence. The objective of this study is to explore the influence of acute nociceptive somatic stimulation in the form of acid injections, into the ipsilateral somatic receptive field of neurones responsive to colorectal distension (CRD), and the potential role of ionotropic glutamate receptors on sensitization. Action potentials of CRD-sensitive SNs were recorded extracellularly from the lumbar (L(2)-L(5)) spinal cord. Stimulus-response functions (SRFs) to graded CRD (10-80 mmHg, 30 s) were constructed before and 30 min after ipsilateral injection of low pH (4.0, 100 microl) saline into the somatic receptive fields. In some experiments, cervical (C(1)-C(2)) spinalization was performed to eliminate supraspinal influence. The selective NMDA receptor antagonist CGS 19755 and AMPA receptor antagonist NBQX were injected (25 micromol kg(-1), i.v.) to examine their influence on sensitization. Three types of neurones were characterized as short-latency abrupt (SLA, n = 24), short latency sustained (SLS, n = 12), and long-latency (LL, n = 6) to CRD. Ipsilateral injection of low pH (4.0) in the somatic receptive field, but not the contralateral gastrocnemius (GN) or front leg muscles, sensitized responses of these neurones to CRD. Spinalization had no influence on the development of low pH-induced sensitization. Both CGS 19755 and NBQX significantly attenuated the sensitized response to CRD in intact and spinalized animals. Acute nociceptive somatic stimulus sensitizes CRD-sensitive SNs receiving viscero-somatic convergence. The sensitization occurs at the spinal level and is independent of supraspinal influence. Ionotropic glutamate receptors in the spinal cord are involved in sensitization.
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PMID:Acute nociceptive somatic stimulus sensitizes neurones in the spinal cord to colonic distension in the rat. 1528 40

Both preclinical and clinical data link glutamate to the migraine pathophisiology. Altered plasma, platelets and cerebrospinal (CSF) glutamate levels have been reported in migraine patients. Chronic migraine is comorbid with several conditions. It has been recently shown chronic migraine comorbidity with fibromyalgia. The objective of this study was to study cerebrospinal fluid glutamate levels in chronic migraine patients with and without fibromyalgia. We studied 20 chronic migraine patients, with and without fibromyalgia, compared to age-sex matched controls. CSF glutamate levels were measured by HPLC. CSF glutamate demonstrated significantly higher levels in patients with fibromyalgia compared to those without fibromyalgia. Patients overall had higher CSF glutamate levels than controls. Mean pain score correlated with glutamate levels in chronic migraine patients. Tender points, the hallmark of fibromyalgia, can be considered as pressure allodynia, and is probably mediated by central sensitization, with increase in CSF glutamate levels. We postulate chronic migraine patients with fibromyalgia, in addition to have more disabling headaches, suffer from a more severe central sensitization process. This subtype of patients may respond to medications modulating glutamate receptors. Headache intensity correlate with glutamate levels in chronic migraine patients.
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PMID:Cerebrospinal fluid glutamate levels in chronic migraine. 1531 29

A young woman presented with multiple central hypersensitivity disorders, including fibromyalgia, headache, pelvic pain and several smooth muscle spasm disorders, including irritable bowel syndrome, irritable bladder and Raynaud's phenomenon. She also had significant fatigue and sleep problems. Her case illustrates the importance and surprising frequency of atypical bipolar mood disorders in people with multiple central hypersensitivity pain disorders, especially with depression and anxiety resistant to antidepressant treatment. Considering neurological mechanisms common to her overlapping disorders was very helpful in guiding treatment choices. This experience illustrates the value of serotonin receptor type 2 (5HT2) inhibition with atypical neuroleptics, of neural cation channel and glutamate inhibition with anticonvulsants, and the potential usefulness of antidepressants after establishing 5HT2 control to enhance downward inhibitory tracts. Medications with combined usefulness for both bipolar mood and pain disorders were highly effective for her multiple hypersensitivity problems.
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PMID:Serotonin mechanisms in pain and functional syndromes: management implications in comorbid fibromyalgia, headache, and irritable bowl syndrome - case study and discussion. 1576 Aug 6

The purpose of the present review is to correlate recent knowledge of the role of peripheral ionotropic glutamate receptors in the temporomandibular joint and muscle pain from animal and human experimental pain models with findings in patients. Chronic pain is common, and many people suffer from chronic pain conditions involving deep craniofacial tissues such as temporomandibular disorders or fibromyalgia. Animal and human studies have indicated that the activation of peripheral ionotropic glutamate receptors in deep craniofacial tissues may contribute to muscle and temporomandibular joint pain and that sex differences in the activation of glutamate receptors may be involved in the female predominance in temporomandibular disorders and fibromyalgia. A peripheral mechanism involving autocrine and/or paracrine regulation of nociceptive neuronal excitability via injury or inflammation-induced release of glutamate into peripheral tissues that may contribute to the development of craniofacial pain is proposed.
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PMID:Neural mechanisms of temporomandibular joint and masticatory muscle pain: a possible role for peripheral glutamate receptor mechanisms. 1617 50

The 5-HT3 receptor is a pentameric ligand-gated cation channel which is found in the central and peripheral nervous system and on extraneuronal locations like lymphocytes, monocytes and fetal tissue. Five monomer subtypes, the 5-HT(3A-E) subunits, have been identified which show differences in the amino-terminal and the transmembrane region. The functional relevance of different receptor compositions is not yet clarified. 5-HT3 receptors are located predominantly in CNS regions that are involved in the integration of the vomiting reflex, pain processing, the reward system and anxiety control. The preferential localization on nerve endings is consistent with a physiological role of 5-HT3 receptors in the control of neurotransmitter release such as dopamine, cholecystokinin, glutamate, acetylcholine, GABA, substance P, or serotonin itself. 5-HT3-receptor agonists cause unpleasant effects like nausea and anxiety, and no clinical use has been considered. In contrast, the introduction of 5-HT3-receptor antagonists for chemotherapy-induced vomiting was extremely successful. After development of other gastrointestinal indications like postoperative vomiting and diarrhea-predominant irritable bowel syndrome recent research focuses on rheumatological indications such as fibromyalgia, rheumatoid arthritis and tendinopathies. Positive effects have also been observed for pain syndromes such as chronic neuropathic pain and migraine. These effects seem to be related to substance P-mediated inflammation and hyperalgesia. Furthermore, antiinflammatory and immunomodulatory properties have been observed for 5-HT3-receptor antagonists which might explain promising findings in systemic sclerosis and other immunological conditions. For all of these innovative indications the optimal dosing schedule is a crucial issue, since a bell-shaped dose-response curve has been observed repeatedly for 5-HT3-receptor antagonists, particularly in CNS effects.
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PMID:The neuronal 5-HT3 receptor network after 20 years of research--evolving concepts in management of pain and inflammation. 1731 6

Recent advances have shed insight on the pathophysiologic mechanisms of fibromyalgia and migraine, especially in the chronic form. A growing body of evidence supports the involvement of peripheral and central sensitization disturbances of pain-related processes underlying both disorders. They involve increased glutamate transmission through interaction with its ionotropic and metabotropic receptors. Few studies supporting the implication of this excitatory amino acid in chronic migraine and primary fibromyalgia demonstrated increased levels of glutamate in the cerebrospinal fluid of affected patients. These findings have implications for future therapies directed against glutamate receptors (in particular, N-methyl-D-aspartate receptors). Limited clinical experience in this regard, although promising, does not exclude additional mechanisms contributing to the maintenance of pain, which can be the target of therapeutic approaches in both disorders.
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PMID:Sensitization, glutamate, and the link between migraine and fibromyalgia. 1789 24

Fibromyalgia (FM) is a chronic musculoskeletal pain disorder often associated with fatigue, dyscognition, and sleep disturbances. Recent research advances highlight a critical role for aberrant central pain processing in FM, and, consistent with these data, the first three drugs approved by the FDA for FM over the past 2 years have a predominantly central mode of action. The first drug, pregabalin, may counteract central pain transmission by inhibiting presynaptic release of excitatory neurotransmitters, including substance P and glutamate. The serotonin-norepinephrine reuptake inhibitors duloxetine and milnacipran have been approved more recently and are believed to reduce pain by increasing serotonin and norepinephrine concentrations in descending inhibitory pain pathways. Agents with multiple other mechanisms of action are in development and promise an assortment of therapeutic options for this complex disorder in the near future.
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PMID:Current progress in the pharmacological therapy of fibromyalgia. 1973 29

Fibromyalgia is the diagnosis given to individuals with chronic widespread musculoskeletal pain for which no alternative cause, such as tissue inflammation or damage, can be identified. Fibromyalgia is now believed to be, at least in part, a disorder of central pain processing that produces heightened responses to painful stimuli (hyperalgesia) and painful responses to nonpainful stimuli (allodynia). Aberrations in central pain processing may also be partly responsible for symptoms experienced in several chronic pain disorders that coaggregate with fibromyalgia, which is itself a product of genetic and environmental factors. Thus, aberrational central pain processing is implicated in irritable bowel syndrome, temporomandibular disorder, chronic low back pain, and certain other chronic pain disorders. Fibromyalgia and related disorders appear to reflect deficiencies in serotonergic and noradrenergic, but not opioidergic, transmission in the central nervous system. The heightened state of pain transmission may also be owing to increases in pronociceptive neurotransmitters such as glutamate and substance P. In some cases, psychological and behavioral factors are also in play. Although the overlapping symptomatology between fibromyalgia and related disorders may present diagnostic challenges, proper examination and observation can help clinicians make an accurate diagnosis. In recent years, the vastly improved understanding of the mechanism underlying fibromyalgia and the related spectrum of diseases has fostered rapid advances in the therapy of these chronic pain disorders by both pharmacologic and nonpharmacologic interventions.
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PMID:Fibromyalgia: an overview. 1996 94


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