Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0030193 (pain)
 261,466 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Pain is a universal, subjective, unpleasant sensation. It results from a noxious stimulus that causes the body to perceive existing or potential damage to its organs. The biochemical mechanism of pain is based on peripheral nociceptors that preferentially receive noxious stimuli and thereafter cause the primary afferent nociceptor fibers to release endogenous chemicals such as bradykinin, histamine, prostaglandins, serotonin, norepinephrine, and substance P. Additionally, substance P may stimulate prostaglandin and collagenase production, thus providing an explanation for the effectiveness of anti-inflammatory drugs in relieving pain. The interpretation of pain is highly individualized and embodies the entire personality. Thus, no two patients with pain can be treated in the same way. Pain is assessed through medical history, physical examination, and a variety of pain scales. General principles in managing pain call for the physician to (1) respect pain; (2) recognize the psychologic components of pain; and (3) treat the underlying disorder in a timely fashion. Modern management of pain evokes a multidisciplinary approach that includes patient education, pharmacologic intervention, physical medicine, minimally invasive procedures, psychologic counseling, behavioral modification and, in some instances, surgery or a variety of other nonpharmacologic modalities.
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PMID:Approach to the management of nonmalignant pain. 876 61

Calcium antagonist increase extracellular matrix collagenase activity as well as decrease collagen, fibronectin synthesis and secretion, altering fibroblastic metabolism. Preliminary findings reports that Verapamil improves would healing; Levine (1994) suggest that intralesional calcium antagonist (Verapamil) therapy offers an economical and sensible non operative approach for the treatment of Peyronie's disease. We studied and verified the effect of Verapamil in Peyronie's plaque on 39 men. They received injections of Verapamil bi-weekly in to the plaques for 6 months. Subjectively, improvement in rigidity was observed in 23,1% and a plaque softening observed in 48,7%. Rapid resolution of pain was verified in 90,9%. Objectively, curvature improved in 50% of those in which the diagnosis of Peyronie's disease was less than one year old, but in only 10.2% when disease lasted more than one year. A decreased plaque volume was not observed. There was no toxicity related to Verapamil effect. In this nonrandomized study we retained that Verapamil appears to result in an improvement in patients with symptoms lasting less than one year. For patients without pain with symptoms related to more than one year, Verapamil had no important effect.
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PMID:[Clinical effects of verapamil in the treatment of Peyronie's disease]. 892 94

Rhein, the active metabolite of diacerein, inhibits interleukin-1 activity. Consequently, collagenase production in articular cartilage is reduced. Rhein dose-dependently inhibits superoxide anion production, chemotaxis and phagocytic activity of neutrophils, and macrophage migration and phagocytosis. Articular cartilage damage is reduced by diacerein in animal models of osteoarthritis. Diacerein does not alter renal or platelet cyclooxygenase activity and may therefore be tolerated by patients with prostaglandin-dependent renal function. In clinical trials of < or = 6 months' duration, oral diacerein 50mg twice daily was associated with improvement in 57 to 85% of patients with osteoarthritis. Pain scores and measures of joint function were generally reduced compared with baseline and placebo. Diacerein had similar efficacy to NSAIDs, but a slower onset of action, in comparative trials of < or = 2 months' duration conducted in patients with osteoarthritis. The predominant adverse effects of diacerein are diarrhoea and related disorders.
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PMID:Diacerein. 901 Jun 51

The present report concerns a patient who had undergone nearly total pancreatectomy (95%) with pancreatic islet autotransplantation for intractable pain caused by obstructive chronic pancreatitis. Islets were prepared by a modified collagenase digestion and were cultured in vitro in Eagel's medium in 5% CO2 in air at 37 degrees C for 5 days. The resultant preparation, containing about 150,000 islets, was injected into the recipient's liver via the umbilical vein. No complication occurred from the pancreatectomy or transplant. Postoperatively, the patient had complete relief of the abdominal pain, and the insulin-independent condition remained with normal fasting blood glucose, and hemoglobin A1c for 11 months. Subsequently the fasting hyperglycemia was evident, and the patient began oral antidiabetic medication, but 2 year after transplantation the insulin-dependent condition demanded exogenous insulin (24 U). At present the fasting serum C-peptide level is 0.6 ng/ml and the HbA1c of 5.8% confirms the normoglycemic condition at the same insulin dose. Islet auto-transplantation should be considered as an adjunct procedure to prevent or ameliorate diabetes after total or nearly total pancreatic resection.
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PMID:[Management of diabetes induced by nearly total (95%) pancreatectomy with autologous transplantation of Langerhans cells]. 928 Aug 85

Tetracyclines exert, independently of their antimicrobial activity, anti-collagenolytic effects by inhibiting activities of human interstitial collagenases and by preventing the oxidative activation of latent pro-collagenases. We tested the clinical response to a 3-month doxycycline in concert with collagenase activity in 12 rheumatoid arthritis (RA) patients. Patients received 150 mg/day of doxycycline for 3 months. Clinical assessments at zero, six and 12 weeks comprised classification of the functional class, joint score index, Hb, CRP, ESR, health assessment questionnaire, visual analogue scale (VAS) of pain, pain disability index, comprehensible psychopathological rating scale (CPRS), SDS-PAGE laser densitometric collagenase activity measurements and Western blots. Significant reductions were seen in joint score index (P < 0.01), pain VAS (P < 0.05) and some CPRS parameters. Furthermore, collagenase activities measured from saliva by quantitative SDS-PAGE electrophoresis were significantly reduced during the 12-week intervention (P < 0.01). Western blots demonstrated intact 75-80 kDa enzyme protein (classic neutrophil collagenase), but also a newly discovered mesenchymal, less glycosylated 40-55 kDa MMP-8 subtype of fibroblast/chondrocytic origin. These results indicate that the documented favourable clinical response may in part be due to in vivo inhibition of classic neutrophil and mesenchymal collagenase/MMP-8 activities produced by doxycycline. This anti-collagenolytic doxycycline effects is mediated through inhibition of the enzyme activity and not through degradation of the enzyme, which may have contributed to the reportedly reduced tissue destruction, as has been seen in clinical studies concerning RA as well as reactive arthritis.
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PMID:Anti-collagenolytic mechanism of action of doxycycline treatment in rheumatoid arthritis. 954 77

Clinical trials with monoclonal antibodies directed against TNF alpha (anti-TNF mAbs) and soluble TNF receptor fusion proteins (sTNFR-IgGs) have demonstrated that systemic and synovial trapping of TNF alpha results in long lasting anti-inflammatory and anti-nociceptive effects in patients with rheumatoid arthritis. Clinical indices of inflammatory synovitis and laboratory parameters (CRP and ESR) respond to single and repeated administrations of anit-TNF alpha therapies in a dose-dependent fashion. Studies on the immuno-pharmacological profile in patients suggest evidence that TNF alpha trapping down-regulates the effector mechanisms involved in the immuno-inflammatory response in rheumatoid arthritis. Inhibition of PLA 2- and COX-2-derived pathways of mediators of inflammation (prostanoids and leukotrienes) decreases signs and symptoms of inflammatory synovitis such as joint swelling, tenderness and pain. Down-regulating of the cytokine-inducible adhesion molecules ICAM-1, VCAM-1 and ELAM-1 in endothelial cells and synoviocytes results in a marked inhibition of transendothelial migration of inflammatory and immune cells. A decrease of cytokine-regulated metalloproteinase expression results in normalization of circulating MMP-1 and MMP-3 levels. The effect of TNF alpha neutralization on mechanisms of rheumatoid joint destruction has the long-term potential for preventing or decreasing the rate of erosive changes of cartilage and bone.
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PMID:[Immunopharmacologic profile and therapeutic prospects of anti-TNF-alpha therapy]. 986 33

Collagenase and gelatinase are matrix metalloproteinases (MMPs) which play an important role in tissue destruction in arthritic joints. Studies have demonstrated that tetracyclines can inhibit MMPs and prevent tissue destruction independent of their antimicrobial activity. The purpose of this pilot study is to assess the potential therapeutic role of Doxycycline in patients with advanced osteoarthritis of the temporomandibular joint (TMJ). This ongoing investigation includes patients with a diagnosis of osteoarthritis of the TMJ based on clinical and diagnostic imaging findings, symptoms (localized TMJ pain, limited mobility, dysfunction) for a minimum of 36 months, and failure of previous non-surgical and surgical modalities to alleviate the symptoms. A synovial fluid sample is collected by a saline injection and aspiration technique, followed by diagnostic arthroscopy. Patients are placed on Doxycycline 50 mg BID for three months and then undergo repeat diagnostic arthroscopy and synovial fluid collection. The samples are stored at -80 degrees C. Collagenase activity is determined by a combination of SDS-polyacrylamide gel electrophoresis and fluorography and calculated based on the percentage of collagen alpha chains that are degraded into alphaA breakdown products. Three patients have completed the three-month course of Doxycycline thus far, and 5 joints with osteoarthritis have been analyzed. All patients were female (mean age = 35, mean duration of symptoms = 132 months) and had undergone previous bilateral arthroscopies. One patient had undergone unilateral arthroplasty. The mean collagenase activity showed 55% collagen lysis prior to Doxycycline treatment and 19% after three months of therapy. The mean gelatinase activity was 28% prior to Doxycycline treatment and 7% after three months of therapy. The mean interincisal opening was 33 mm initially and 41 mm after three months of Doxycycline. Subjectively, two of the three patients reported significant improvement in their overall symptoms, which they had not experienced over the previous three years. One patient did not experience any change in symptoms, in spite of a marked reduction in collagenase activity from 86.4% to 9.6%. Because of the very small numbers of patients enrolled in this pilot study so far, no statistically significant differences could be appreciated. However, the dramatic reduction in collagenase activity in these patients, with a long history of TMJ symptoms from osteoarthritis, suggests the potential promising role of Doxycycline in the management of osteoarthritis, and further investigation is warranted.
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PMID:The potential role of doxycycline in the treatment of osteoarthritis of the temporomandibular joint. 997 22

We measured matrix metalloproteinases (MMPs) and tissue inhibitor of metalloproteinases (TIMP) in temporomandibular joint (TMJ) disorders. All patients were fully investigated, by visual analogue pain scores, plain radiographs and double-contrast arthrotomograms. The patients were grouped according to whether or not they were in pain. There were 35 patients with painful joints; 16 painless crepitating joints and 10 with chronic closed locked joints. A further group of 9 volunteers with no symptoms of TMJ abnormalities were used as controls. We found that synovial fluid concentration of MMP-3 was significantly increased (1117.2 (164.0) ng/ml) (P< 0.05) in the painful group compared with controls (436.2 (94.8) ng/ml) and with the two groups with painless TMJ (475.0 (113. 0) ng/ml/crepitation, and 516.0 (115.1) ng/ml/closed locked joints). MMP-1 and TIMP-1 were not recordable in most joints, and the serum concentrations of MMP-1, MMP-3, and TIMP-1 were similar to those in controls in all groups. There was no correlationship between MMP-3 concentration and joint morphology as shown by plain radiographs and double contrast arthrotomograms. These findings indicate that the synovia of painful joints are inflamed.
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PMID:Matrix metalloproteinase and tissue inhibitor of metalloproteinase in serum and lavage synovial fluid of patients with temporomandibular joint disorders. 1092 68

Orthodontic treatment is based on the biologic principle that prolonged pressure on teeth results in remodeling of periodontal structures, allowing for tooth movement. Periodontal remodeling is a complex process regulated in part by prostaglandins and adversely affected by the use of nonsteroidal anti-inflammatory drugs. We investigated the effects of indomethacin on collagenase activity and procollagen synthesis in rat endothelial cell cultures. Cyclooxygenase inhibition resulted in exacerbation of IL-1 beta-mediated collagenase B (MMP-9) production and activity, as well as attenuation of type IV procollagen synthesis levels by endothelial cells in vitro. Hence, the use of over-the-counter nonsteroidal anti-inflammatory drugs during tooth movement may result in aberrant remodeling of periodontal vasculature and other structures, ultimately affecting orthodontic treatment efficacy. Further studies are needed to establish novel pain relievers that do not interfere with orthodontic processes.
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PMID:Nonsteroidal anti-inflammatory drugs in orthodontic tooth movement: metalloproteinase activity and collagen synthesis by endothelial cells. 1093 62

Nimesulide (Aulin) refers to the class of sulphonanilides, which is unique among the non-steroidal antiinflammatory drugs (NSAIDs), being also the first drug on the market of pharmaceuticals, which preferentially inhibits the enzyme cyclooxygenase-2 (COX-2). This enzyme takes part in the synthesis of prostaglandin, which is produced in the course of the cascade of the inflammation process and has relation to the pathogenesis of pain, inflammation and fever, while the COX-1 enzyme forms prostaglandin, which projects the gastro-intestinal mucosis. Many newly found factors, together with the preferential inhibition of COX-2, are also contributing to the therapeutic effects of Nimesulide. The therapeutic concentration of non-combined active substance in blood-circulation reduces the following indicators: the activity of the myeloperoxidase; the release of cytokines; the histamine effects; the synthesis of stromelysin and collagenase, which pull down the proteoglicans and collagen. It is also characteristic of Nimesulide its antioxidant activity and suppression of: the synthesis of superoxidic ions from the neutrophils; also, the synthesis of platelet activating factor. Nimesulide shows good tolerability and is safe with patients having respiratory problems due to treatment with other NSAIDs.
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PMID:[Nimesulide - a non-steroidal anti-inflammatory drug, a preferential cyclooxygenase-2 inhibitor]. 1119 95


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