UMLS:C0030193 - FACTA Search

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Query: UMLS:C0030193 (pain)
261,466 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Increased spinal cyclooxygenase activity is associated with nociception induced by tissue inflammation. In the present study, we examined the changes of cyclooxygenase-1 and cyclooxygenase-2 protein expression in several regions of the CNS associated with pain perception, and the role of spinal cyclooxygenase activity in the development of allodynia following nerve injury. Allodynia was induced by ligation of the left L5 and L6 spinal nerves in rats. Using western blot analysis, we found that the cyclooxygenase-2 protein levels in the dorsal spinal cord and thalamus (but not in the ventral spinal cord, cingulate cortex and locus coeruleus) increased significantly one day after nerve ligation, compared with those in the sham animals. The cyclooxygenase-2 protein levels in the above tissues were similar in nerve-injured and sham animals three and 14 days after surgery. In contrast, cyclooxygenase-1 protein was not detectable in any of the neural tissues examined one, three, and 14 days after nerve injury. In the behavioral experiments, we observed that intrathecal injection of 100microg of indomethacin immediately or one day after nerve ligation attenuated the development of tactile allodynia. However, intrathecal injection of indomethacin had no effect on established allodynia two weeks after nerve injury.Collectively, our results suggest that cyclooxygenase-2 is preferentially up-regulated in the dorsal spinal cord and thalamus in response to nerve injury in rats. Spinal cyclooxygenase-2 probably plays an important role in the early development, but not in the maintenance, of tactile allodynia caused by the nerve injury in this rat model of neuropathic pain.
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PMID:Spinal cyclooxygenase-2 is involved in development of allodynia after nerve injury in rats. 1084 19

Nonsteroidal anti-inflammatory drugs (NSAIDs) are among the most widely prescribed medications worldwide and are often the first choice of treatment for acute myalgias, orthopedic injuries, postoperative pain, chronic rheumatoid arthritis, and osteoarthritis. The mechanism through which NSAIDs provide analgesia and suppress inflammation is the inhibition of the enzyme cyclooxygenase, resulting in decreased prostaglandin synthesis. The suppression of prostaglandin synthesis can also produce gastric and renal toxicity, as well as impair normal platelet function. Thus, NSAIDs are associated with potentially harmful side effects. Cyclooxygenase exists in two isoenzymatic forms, cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2). Cyclooxygenase-1 appears to be constitutively expressed in many tissues and produces prostaglandins, which regulate normal cellular functions. However, COX-2 activity is induced by proinflammatory cytokines and produces prostaglandins that mediate the inflammatory response and pain signaling transmission. Traditional nonspecific NSAIDs inhibit both COX-1 and COX-2, and in doing so, not only decrease inflammation and pain, but also promote gastrointestinal tract damage and bleeding. The potential clinical benefit of COX-2 inhibitors is significant due to the number of patients chronically treated with NSAIDs and the three- to ten-fold higher risk of gastrointestinal injury and death associated with traditional NSAIDs. Recently, a class of anti-inflammatory medications has been developed that primarily inhibits COX-2 while sparing the enzymatic activity of COX-1 at therapeutic dosages. Two medications that predominantly inhibit only COX-2, rofecoxib and celecoxib, are currently available by prescription in the United States.
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PMID:COX-2 specific inhibitors offer improved advantages over traditional NSAIDs. 1091 95

Arthritis does not escape the athlete. From the recreational athlete to the professional athlete, arthritis can be a common and perplexing problem. In the typical orthopedic sports medicine practice, it is no longer uncommon to see relatively young patients suffering from arthritis. It can affect the major joints such as the knee, hip, ankle, shoulder, and elbow. One of the most common problems is shoulder arthritis secondary to injury in recreational athletes. Athletes at risk for shoulder arthritis typically include overhead athletes and weight lifters. The clinical presentation is usually specific for pain, decreased range of motion, and sometimes mechanical symptoms. Physical examination reveals a loss of motion, crepitus, catching, and locking; often, there is associated underlying instability. Radiographs can confirm the diagnosis of glenohumeral degenerative arthritis. Pain control is a primary objective when treating these athletes with arthritis at any level. Cyclooxygenase-2 (COX-2) specific inhibitors are emerging as primary treatment because of their anti-inflammatory and analgesic effect. Although a nonsteroidal anti-inflammatory drugs, COX-2 inhibitors block the enzymes that trigger pain and inflammation, while sparing a related enzyme that helps maintain the normal stomach lining (cyclooxygenase-1). In contrast, traditional nonsteroidal anti-inflammatory drugs block both enzymes and may cause damage to the stomach lining, potentially leading to ulcers. Minimally invasive surgery can be performed as a palliative procedure for treating early arthritis in athletes. These procedures include removal of loose bodies, debridement, capsular release, and other associated procedures such as rotator cuff repair and decompression. Rehabilitation plays an important role in nonoperative treatment and also an important role in postoperative treatment particularly to restore motion. Modification of activities continues to be an important adjunct in managing these types of arthritic problems in relatively young athletes.
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PMID:Current concepts in sports medicine: the use of COX-2 specific inhibitors and the emerging trends in arthroscopic surgery. 1091 97

Prostaglandins formed by cyclooxygenase-1 (COX-1) or COX-2 produce hyperalgesia in sensory nerve endings. To assess the relative roles of the two enzymes in pain processing, we compared responses of COX-1- or COX-2-deficient homozygous and heterozygous mice with wild-type controls in the hot plate and stretching tests for analgesia. Preliminary observational studies determined that there were no differences in gross parameters of behavior between the different groups. Surprisingly, on the hot plate (55 degrees C), the COX-1-deficient heterozygous groups showed less nociception, because mean reaction time was longer than that for controls. All other groups showed similar reaction times. In the stretching test, there was less nociception in COX-1-null and COX-1-deficient heterozygotes and also, unexpectedly, in female COX-2-deficient heterozygotes, as shown by a decreased number of writhes. Measurements of mRNA levels by reverse transcription-PCR demonstrated a compensatory increase of COX-1 mRNA in spinal cords of COX-2-null mice but no increase in COX-2 mRNA in spinal cords of COX-1-null animals. Thus, compensation for the absence of COX-1 may not involve increased expression of COX-2, whereas up-regulation of COX-1 in the spinal cord may compensate for the absence of COX-2. The longer reaction times on the hot plate of COX-1-deficient heterozygotes are difficult to explain, because nonsteroid anti-inflammatory drugs have no analgesic action in this test. Reduction in the number of writhes of the COX-1-null and COX-1-deficient heterozygotes may be due to low levels of COX-1 at the site of stimulation with acetic acid. Thus, prostaglandins made by COX-1 mainly are involved in pain transmission in the stretching test in both male and female mice, whereas those made by COX-2 also may play a role in the stretching response in female mice.
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PMID:Nociception in cyclooxygenase isozyme-deficient mice. 1095 56

Nonsteroidal antiinflammatory drugs (NSAID) are among the most widely prescribed medications worldwide. While these agents are efficacious for the relief of both pain and the signs and symptoms of inflammation, the use of traditional NSAID is associated with a high prevalence of toxic events. It is estimated that 2-4% of traditional NSAID users will have a serious adverse gastrointestinal (GI) event per year, with a point prevalence of GI ulcers at any given time of 10-30%. The mortality rate associated with these NSAID is one of the highest attributed to the use of any agent. Prostaglandin replacement with misoprostol has been shown to significantly reduce the incidence of serious GI toxicity related to the use of conventional NSAID. All conventional NSAID inhibit both cyclooxygenase-1 (COX-1) and COX-2 enzymes. As COX-1 is constitutively expressed in many tissues and contributes to the maintenance of the normal physiologic state in the GI tract, the kidney, and platelets, an agent that specifically inhibits COX-2, an inducible enzyme associated with the inflammatory response, would be highly desirable. Specific COX-2 inhibition would have the advantage of improving the signs and symptoms of inflammation, while avoiding the possibly significant toxicity of traditional NSAID. This article describes the biology of eicosanoids and the effects of NSAID, the toxicity profile of conventional NSAID, and the rationale for the use of gastroprotective agents or agents that specifically inhibit the COX-2 isozyme.
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PMID:From prostaglandin replacement to specific COX-2 inhibition: a critical appraisal. 1103 96

Cyclooxygenase-2 (COX-2) inhibitors constitute a new group of non-steroidal anti-inflammatory drugs (NSAIDs) which, at recommended doses, block prostaglandin production by cyclooxygenase-2, but not by cyclooxygenase-1. Two COX-2 inhibitors are currently available in Australia--celecoxib, which is taken twice daily, and rofecoxib, which is taken once daily. Both drugs act rapidly in providing pain relief and their anti-inflammatory analgesic effect in osteoarthritis and rheumatoid arthritis is equivalent to standard doses of non-selective NSAIDs. Celecoxib and rofecoxib show significantly lower incidences of gastrotoxicity (as measured by endoscopic studies and gastrointestinal ulcers and bleeds) than non-selective NSAIDs. There is Level 2 evidence that COX-2 inhibitors: reduce pain in classic pain models--third-molar extraction, dysmenorrhoea and after orthopaedic surgery; reduce pain and disability in osteoarthritis of the hip and knee; and reduce pain and disability in rheumatoid arthritis. Other adverse effects, such as interference with antihypertensive agents and the potential to produce renal dysfunction in patients with compromised renal function by COX-2 inhibitors, seem similar to those of non-selective NSAIDs.
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PMID:COX-2 inhibitors. 1134 18

Relevant aspects of pain physiology and anatomy are reviewed, including hyperalgesia (an exaggerated response to normally mild stimuli) and allodynia (pain in response to normally non-noxious stimuli). Although the principal animal models do an excellent job at separating thermal, mechanoreceptor, and visceral aspects of pain, they are not very good predictive models because human pain is more complex. Human pain includes overlapping aspects of specific pain types, such as spontaneous and induced pain, and is modified by gender, stress, states of vigilance, and depression. Nonsteroidal anti-inflammatory drugs (NSAIDs) have both peripheral and central analgesic effects. While prostaglandin-mediated effects are clearly operative, there are also other potential mechanisms involved in many cases and these may be quite important in certain patients. Effects mediated by cyclooxygenase-1, leukotriene B4, and intracellular transcription elements such as peroxisomal proliferator-activated receptors gamma (PPARgamma) may account for part of the spectrum of NSAID actions. Future directions for analgesic research are many, but include the use of nitric oxide (NO) NSAIDs; the possibility of decreasing NO in the central nervous system; inhibiting the vanilloid receptor-1; inhibiting adenosine kinase; activating PPARgamma; and mimicking superoxide dismutase, as well as combinations of complementary-acting analgesics.
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PMID:Future directions in pain management. 1169 56

Nociception evoked prostaglandin (PG) release in the spinal cord considerably contributes to the induction of hyperalgesia and allodynia. To evaluate the relative contribution of cyclooxygenase-1 (COX-1) and COX-2 in this process we assessed the effects of the selective COX-1 inhibitor SC560 and the selective COX-2 inhibitor celecoxib on formalin-evoked nociceptive behaviour and spinal PGE(2) release. SC560 (10 and 20 mg/kg) significantly reduced the nociceptive response and completely abolished the formalin-evoked PGE(2) raise. In contrast, celecoxib (10 and 20 mg/kg) was ineffective in both regards, i.e. the flinching behaviour was largely unaltered and the formalin-induced PGE(2) raise as assessed using microdialysis was only slightly, not significantly reduced. This suggests that the formalin-evoked rapid PG release was primarily caused by COX-1 and was independent of COX-2. Mean free spinal cord concentrations of celecoxib during the formalin assay were 32.0 +/- 4.5 nM, thus considerably higher than the reported IC50 for COX-2 (3-7 nM). Therefore, the lack of efficacy of celecoxib is most likely not to be a result of poor tissue distribution. COX-2 mRNA and protein expression in the spinal cord were not affected by microdialysis alone but the mRNA rapidly increased following formalin injection and reached a maximum at 2 h. COX-2 protein was unaltered up to 4 h after formalin injection. The time course of COX-2 up-regulation suggests that the formalin-induced nociceptive response precedes COX-2 protein de novo synthesis and may therefore be unresponsive to COX-2 inhibition. Considering the results obtained with the formalin model it may be hypothesized that the efficacy of celecoxib in early injury evoked pain may be less than that of unselective NSAIDs.
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PMID:Effects of selective COX-1 and -2 inhibition on formalin-evoked nociceptive behaviour and prostaglandin E(2) release in the spinal cord. 1172 70

Rheumatoid arthritis (RA) is a systemic inflammatory disease with polyarticular synovitis leading to formation of rheumatoid pannus and subsequent erosion of articular cartilage and bone. Prostaglandins (PGs)--a group of arachidonic acid metabolites found at elevated levels in synovial fluid and synovial membrane are considered to play a pivotal role in development of vasodilatation, fluid extravasation and pain in synovial tissues. Moreover, there is increasing evidence that PGs (especially prostaglandin E2) are mediators involved in complex interactions leading to development of erosions of articular cartilage and juxta-articular bone. Cyclooxygenase is an enzyme playing crucial role in PGs production. It is known that two forms of cyclooxygenase exist: cyclooxygenase-1 (COX-1) playing house-keeping functions and cyclooxygenase-2 (COX-2) involved in inflammatory responses. Synovial tissues from patients with RA are shown to contain COX-2 and to a less extent COX-1. COX-2 expression in rheumatoid synovium is induced by proinflammatory cytokines, mainly IL-1, while corticosteroids are capable of inhibiting COX-2 expression. The understanding of crucial role of COX-2 in synovial inflammation led to development of new group of anti-inflammatory agents--selective COX-2 inhibitors, that inhibit specifically COX-2, providing effective anti-inflammatory action without the side effects associated with inhibition of COX-1. In the context of widespread use of selective COX-2 inhibitors hypothetical role of COX-1 in RA pathology should be elucidated.
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PMID:[The role of cyclooxygenase and prostaglandins in the pathogenesis of rheumatoid arthritis]. 1185 19

Osteoid osteoma is a benign bone forming neoplasm that is characterized by its small size (less than 2 cm), self-limited growth, and the tendency to cause extensive reactive changes in the adjacent tissue. The lesion classically presents with severe pain at night that is dramatically relieved by NSAIDs. The tumor has been shown to express very high levels of prostaglandins, particularly PGE2 and PGI2. The high local levels of these prostaglandins are presumed to be the cause of the intense pain seen in patients with this lesion. One generally accepted form of treatment is the prolonged use of NSAIDs. Since the cyclooxygenases are thought to be the source of these prostaglandins, and the central target of NSAIDs, we evaluated the expression of cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2) in osteoid osteoma tissues from patients following surgery. In the 12 specimens examined we found that the tumor osteoblasts had strong immunohistochemical staining for COX-2, while the staining in the surrounding host osteoblasts in the reactive bone was scant. Significant COX-1 staining was also detected in both tumor and host osteoblasts. For comparison we examined the COX expression in human fracture callus, fibrous dysplasia, osteoblastoma, osteofibrous dysplasia, and myositis ossificans. With the exception of fracture callus, very limited amounts of COX-2 could be detected in these tissues. Taken together, we conclude that the increased production of prostaglandins by osteoid osteomas implicates that COX-2 is one of the mediators of this condition. These findings suggest that the newly selective COX-2 inhibitors could be used to more safely treat osteoid osteomas.
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PMID:COX-1 and COX-2 expression in osteoid osteomas. 1600 74

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