Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0018099 (gout)
 5,192 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Pain-induced functional impairment in the rat (PIFIR) is a model of inflammatory and arthritic pain similar to that of clinical gout. Nociception is induced by the intra-articular injection of uric acid into the right hind limb, inducing its dysfunction. Animals then receive analgesic drugs and the recovery of functionality over time is assessed as an expression of antinociception. We have examined the role of peripheral prostaglandins synthesized by cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2) in inflammatory pain using the PIFIR model. Rofecoxib (a selective COX-2 inhibitor) and SC-560 (a selective COX-1 inhibitor) both produced dose-dependent effects. When the inhibitors were administered before uric acid, they showed similar potency, but the antinociceptive efficacy of SC-560 was lower than rofecoxib; the best antinociceptive effects were obtained with the dose of 100 microg/articulation of each inhibitor (pre-treatment). In post-treatment (inhibitors administered after the uric acid), rofecoxib showed the least antinociceptive effect and SC-560 was more potent than rofecoxib. The inhibition of both COX-1 and COX-2 produced a more profound analgesic effect than the inhibition of either COX-1 or COX-2 alone. The present data support the idea that both COX isoforms contribute to the development and maintenance of local inflammatory nociception. Thus, it could be expected that inhibition of both COX-1 and COX-2 is required for non-steroidal anti-inflammatory drugs (NSAID)-induced antinociception in the rat. These findings suggest that the therapeutic effects of NSAIDs may involve, at least in part, inhibition of COX-1 and COX-2.
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PMID:Involvement of peripheral cyclooxygenase-1 and cyclooxygenase-2 in inflammatory pain. 1190 7

Osteoarthritis (OA) and rheumatoid arthritis (RA) are among the most prevalent chronic illnesses and leading causes of disability in the United States. The clinical symptoms of OA and RA, pain and inflammation, are biologic processes mediated in part by prostanoids-prostaglandins, prostacyclin, and thromboxanes. The intermediate enzymes responsible for prostaglandin biosynthesis, cyclooxygenase (COX)-1 and COX-2, have been the target of arthritis therapy using nonselective nonsteroidal anti-inflammatory drugs (NSAIDs). An understanding of the biochemistry and molecular pharmacology of COX enzymes has allowed for the development of agents that specifically inhibit COX-2. COX-2-selective inhibitors have efficacy in OA and RA that is similar to that of NSAIDs but with a lower potential for upper gastrointestinal injury, a serious side effect of nonselective NSAIDs. COX-2-selective inhibitors have been increasingly used in the treatment of OA and RA as well as other inflammatory arthropathies including ankylosing spondylitis and gout. Clinical trials with two currently available drugs, rofecoxib and celecoxib, have demonstrated efficacy comparable to nonselective NSAIDs but with a lower risk of gastrointestinal side effects. In general, these drugs are well tolerated in patients with aspirin-sensitive asthma. Rofecoxib is well tolerated in patients with sulfonamide sensitivities; further studies are needed to fully characterize the utility of celecoxib in these patients. Clinical experience shows that because of their improved GI safety, rofecoxib and celecoxib, and newer COX-2-selective inhibitors (valdecoxib, etoricoxib, parecoxib), represent a significant advance in the treatment of arthritis and other related inflammatory conditions.
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PMID:Development and clinical application of COX-2-selective inhibitors for the treatment of osteoarthritis and rheumatoid arthritis. 1208 94