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)

Electroacupuncture (EA) can effectively control the exaggerated pain in humans with inflammatory disease and animals with experimental inflammatory pain. However, there have been few investigations on the effect of co-administration of EA and analgesics and the underlying synergistic mechanism. Using behavioral test, RT-PCR analysis, enzyme immunoassay (EIA) and enzyme-linked immunosorbent assay (ELISA), the present study demonstrated that (1) Unilateral intra-articular injection of complete Freund's adjuvant (CFA) produced a constant hyperalgesia and an up-regulation of the prostaglandin E(2) (PGE(2)) level as well as the tumor necrosis factor (TNF)-alpha, interleukin (IL)-1beta, and IL-6 levels in the spinal cord; (2) Celecoxib, a selective inhibitor of cyclooxygenase-2 (COX-2), at a dose of 2, 10, and 20 mg/kg (twice daily, p.o.), presented a dose-dependent anti-hyperalgesic effect; (3) Repeated EA stimulation of ipsilateral 'Huan-Tiao' (GB30) and 'Yang-Ling-Quan' (GB34) acupoints significantly suppressed CFA-induced hyperalgesia, and markedly inhibited the CFA-induced increase of the level of PGE(2) as well as IL-1beta, IL-6, and TNF-alpha in the spinal cord; (4) EA combined with low dose of celecoxib (2 mg/kg, twice daily, p.o.) greatly enhanced the anti-hyperalgesic effects of EA, with a synergistic reversing effect on CFA-induced up-regulation of spinal PGE(2), but not on the IL-1beta, IL-6, or TNF-alpha. These data indicated that repeated EA combined with low dose of celecoxib produced synergistic anti-hyperalgesic effect in the CFA-induced monoarthritic rats, which could be made possible by regulating the activity of spinal COX, hence the spinal PGE(2) level. Thus, this combination may provide an effective strategy for pain management.
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PMID:Synergistic anti-hyperalgesia of electroacupuncture and low dose of celecoxib in monoarthritic rats: involvement of the cyclooxygenase activity in the spinal cord. 1872 68

Lumiracoxib is a COX2 inhibitor that is highly selective, is more effective than placebo on pain in osteoarthritis (OA), with similar analgesic and anti-inflammatory effects as non-selective NSAIDs and the selective COX2 inhibitor celecoxib, has a lower incidence of upper gastrointestinal (GI) side effects in patients not taking aspirin, and a similar incidence of cardiovascular (CV) side effects compared to naproxen or ibuprofen. In the context of earlier guidelines and taking into account the GI and CV safety results of the TARGET study, lumiracoxib had secured European Medicines Agency (EMEA) approval with as indication symptomatic treatment of OA as well as short-term management of acute pain associated with primary dysmenorrhea and following orthopedic or dental surgery. In the complex clinical context of efficiency and safety of selective and non-selective COX inhibitors, its prescription and use should be based on the risk and safety profile of the patient. In addition, there is further need for long-term GI and CV safety studies and general post-marketing safety on its use in daily practice. Meanwhile, at the time of submission of this manuscript, the EMEA has withdrawn lumiracoxib throughout Europe because of the risk of serious side effects affecting the liver.
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PMID:Efficacy and tolerability of lumiracoxib, a highly selective cyclo-oxygenase-2 (COX2) inhibitor, in the management of pain and osteoarthritis. 1872 96

Cyclooxygenase (COX; prostaglandin G/H synthase, EC 1.14.99.1) catalyzes the first two steps in the biosynthesis of prostaglandins (PGs). The two COX isoforms COX-1 and COX-2 are the targets of the widely used nonsteroidal anti-inflammatory drugs, indicating a role for these enzymes in pain, fever, inflammation, and tumorigenesis. The ubiquitous constitutive expression of COX-1 and inducible expression of COX-2 have led to the widely held belief that COX-1 produces homeostatic PGs, while PGs produced by COX-2 are primarily pathophysiological. However, recent discoveries call this paradigm into question and reveal as yet underappreciated functions for both enzymes. This review focuses on some of these new insights.
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PMID:Cyclooxygenases: structural and functional insights. 1895 71

The main COX inhibitors are the non-steroidal anti-inflammatory drugs (NSAIDs). NSAIDs exert anti-inflammatory and analgesic effects through the inhibition of prostaglandin synthesis by blocking COX activity. Currently two COX isoenzymes are known, COX-1 and COX-2. Prostaglandins influenced by COX-1 maintain the integrity of the gastric mucosa. On the other hand, prostaglandins influenced by COX-2 mediate the inflammatory process. The common anti-inflammatory drugs (like aspirin, ibuprofen, and naproxen) all act by blocking the action of both the COX-1 and COX-2 enzymes. The COX-2 inhibitors represent a new class of drugs that do not affect COX-1, but selectively block COX-2. This selective action provides the benefits of reducing inflammation without irritating the stomach. This review will focus on the most recent developments published in the field, paying particular attention to promising COX-2 inhibitors, their chemistry and biological evaluation, and to new chemical and pharmaceutical processes. Moreover, we will discuss recent patents of structural analogs of the COX-2 inhibitors celecoxib and valdecoxib, and novel potential pyridazine, triazole, indole, thione derivatives as a future target for the treatment of inflammation, pain and other diseases.
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PMID:Targeting inhibition of COX-2: a review of patents, 2002-2006. 1907 73

Opioids and non-steroidal anti-inflammatory drugs (NSAIDs) are used to relieve acute and chronic pain. The purpose of this study was to determine the degree of interaction between dexketoprofen and NSAID examples of COXs inhibitors using the isobolographic analysis in the formalin orofacial test in mice. The drugs, i.p., induced a dose-dependent antinociception with different potencies in both test phases. Combinations of dexketoprofen with naproxen, nimesulide, ibuprofen or paracetamol on the basis of the fixed ratio (1:1) of their ED(50)'s values alone demonstrated synergism in both phases. This is important since the orofacial pain is a test not currently used in mice; the drugs are all analgesic for humans and phase II is representative of inflammatory pain. The synergism was: COX-3>COX-2>COX-1 inhibitors, this is particularly interesting since the inhibitor of COX-3, paracetamol, displayed a robust anti-inflammatory activity in an assay of acute and inflammatory pain that mimics inflammatory pain in humans. In conclusion, the synergism of the dexketoprofen/NSAID combinations may improve this type of therapeutic profile, since with low doses of the components, side effects are not likely to occur, and they may be used in long-term treatments.
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PMID:Synergism between NSAIDs in the orofacial formalin test in mice. 1916 21

In this second article we describe the more interesting pharmacological interactions in dental practice based on the prescription of analgesic narcotics, paracetamol and non-selective non-steroid anti-inflammatory drugs (NSAI) (which inhibit cyclooxigenase 1 -COX 1- and cyclooxigenase 2 -COX 2-) and selective NSAIs (COX 2 inhibitors). The importance of preventing the appearance of these pharmacological interactions is because these are medicaments prescribed daily in odontology for moderate pain treatment and inflammation in the oral cavity. Paracetamol can interact with warfarin and therefore care should be taken with chronic alcoholic patients. All NSAIs reduce renal blood flow and consequently are capable of reducing the efficacy of medicaments used for treating arterial hypertension, which act via a renal mechanism. Especial attention should be taken considering the risk of interaction between the antagonists of AT1 receptors of angiostensin II (ARAII) and the NSAIs.
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PMID:Pharmacological interactions of anti-inflammatory-analgesics in odontology. 1917 55

Celecoxib is a selective inhibitor of cyclooxygenase-2 (COX-2) and blocks prostaglandin (PG) biosynthesis associated with inflammatory conditions. In a model of peripherally induced inflammatory pain in rats, celecoxib, given systemically, induced a state of hypoalgesia where the nociceptive threshold was raised above basal values, an effect not observed after treatment with non-selective inhibitors of COX (indomethacin, piroxicam). Here, we have assessed the possibility that these atypical effects of celecoxib could be mediated by action at a site in the CNS. Inflammation and hyperalgesia were induced in one hind paw of rats by intraplantar injection of carrageenan (250microg). Nociceptive thresholds to mechanical stimulation were measured in the inflammed and contralateral paws for 6h after carrageenan injection. Celecoxib, SC236 (selective COX-2 inhibitors), indomethacin (non-selective COX inhibitor), SC560 (selective COX-1 inhibitor) or morphine were given by i.c.v. injection, 30 min before carrageenan. Celecoxib, SC236 or morphine-induced hypoalgesia whereas, after indomethacin or SC 560, the nociceptive threshold only returned to basal values. Naltrexone, also given i.c.v., reversed the hypoalgesia after celecoxib or morphine. Bestatin, an inhibitor of metabolism of endogenous opioid peptides, given i.c.v., potentiated the analgesic effects of a low dose of celecoxib. Taken together, these data indicate that celecoxib could act centrally after systemic administration to produce its characteristic profile of analgesia in this model of peripheral inflammatory pain. Moreover, this atypical analgesia appeared to be mediated by endogenous opioids rather than by inhibition of PG biosynthesis.
Pain 2009 Mar
PMID:The analgesic actions of centrally administered celecoxib are mediated by endogenous opioids. 1918 2

Understanding the neurobiology of pain in naturally occurring models of osteoarthritis (OA) may improve the understanding of human OA pain. Both COX and LOX have been associated with joint pain. This study evaluated COX-1, COX-2, and 5-LOX expression and activity in a naturally occurring canine model of secondary OA. Hip joint capsule with synovial tissue (HJC) and femoral head subchondral bone (FH) was collected from normal dogs and dogs undergoing total hip replacement for coxofemoral joint OA. Tissues were analyzed for COX-1, COX-2, and LOX protein, and PGE(2) and LTB(4). Significantly more COX-2 protein was present in OA HJC than normal joints (p = 0.0009). There was no significant difference in COX-1 or LOX protein, although LOX protein was increased (p = 0.069). PGE(2) concentration in normal and OA HJC was similar (p = 1.0). LTB(4) concentration in OA HJC was significantly greater than normal HJC (p = 0.028). Significantly more COX-1 (p = 0.0098), COX-2 (p = 0.0028), and LOX (p = 0.0095) protein was present in OA FH tissue compared to normal FH tissue. There were no differences in PGE(2) or LTB(4) concentration in normal and OA FH tissue (p = 0.77 and p = 0.11). Together, these data suggest both COX-2 and 5-LOX are appropriate targets for the management of pain associated with naturally occurring OA.
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PMID:Expression and activity of COX-1 and 2 and 5-LOX in joint tissues from dogs with naturally occurring coxofemoral joint osteoarthritis. 1927 54

Nonsteroidal antiinflammatory drugs (NSAIDs) are used to reduce inflammatory response and pain. These drugs have been reported to impair bone metabolism. Parecoxib, a specific COX-2 inhibitor, exerts an inhibitory effect on the mineralization of fracture callus after a tibial fracture in rats. Decreased bone mineral density (BMD) at a fracture site may indicate impairment of early healing, casting doubt on the safety of using COX-2 inhibitors during the early treatment of diaphyseal fractures. Forty-two female Wistar rats were randomly allocated to three groups. They were given parecoxib, indomethacin, or saline intraperitoneally for 7 days after being subjected to a closed tibial fracture stabilized with an intramedullary nail. Two and 3 weeks after surgery, the bone density at the fracture site was measured using dual energy xray absorptiometry (DEXA). Three weeks after the operation the rats were euthanized and the healing fractures were mechanically tested in three-point cantilever bending. Parecoxib decreased BMD at the fracture site for 3 weeks after fracture, indomethacin for 2 weeks. Both parecoxib and indomethacin reduced the ultimate bending moment and the bending stiffness of the healing fractures after 3 weeks. These results suggest COX inhibitors should be avoided in the early phase after fractures.
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PMID:Parecoxib and indomethacin delay early fracture healing: a study in rats. 1931 14

Rice bran, the outer bran and germ of the kernel and a by-product of rice milling, is rich in phytonutrients but has been underutilized because of lipid content instability. New methods for the processing of rice bran have yielded a stabilized form that is increasingly used in foods and dietary supplements. Recent studies have documented a role for stabilized rice bran (SRB) in treating diabetes and arthritis, although little is known of the bioactive compounds that impart these health benefits. Here we characterize the chemical composition of three extracts of SRB and identify the functional bioactives contributing to the inhibitory properties against three key pro-inflammatory enzymes (cyclooxygenase [COX] 1, COX2, and 5-lipoxygenase [5-LOX]) that control the inflammatory cascade involved in impaired joint health, pain, and arthritis. One extract (SRB-AI) demonstrated significant COX1 and COX2 inhibitory activities with 50% inhibitory concentration (IC(50)) values for COX1 and COX2 of 305 and 29 microg/mL, respectively, but no 5-LOX inhibition. The second extract (SRB-AII) inhibited COX1, COX2, and 5-LOX with IC(50) values of 310, 19, and 396 microg/mL, respectively. The third extract (SRB-AIII), a blend of SRB-AI and SRB-AIII, inhibited COX1, COX2, and 5-LOX with respective IC(50) values of 48, 11, and 197 microg/mL. Analysis of the extracts by direct analysis in real time time of flight-mass spectrometry revealed that SRB-AI, SRB-AII, and SRB-AIII contain over 620, 770, and 810 compounds, respectively. Of these, 17 were identified as key bioactives for COX and/or LOX inhibition. These SRB extracts have applications for functional foods and dietary supplements for control of inflammation and joint health.
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PMID:Pro-inflammatory enzymes, cyclooxygenase 1, cyclooxygenase 2, and 5-lipooxygenase, inhibited by stabilized rice bran extracts. 1962 11


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