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Query: UMLS:C0344307 (analgesia)
 28,200 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Opioid agents are highly effective analgesics after orthopedic surgery but are associated with several adverse effects. Valdecoxib is a new, highly selective cyclooxygenase (COX)-2-specific inhibitor with a rapid onset of action and significant analgesic properties that is being developed for the management of acute pain. The objective of this study was to demonstrate the opioid-sparing efficacy of valdecoxib as part of a multimodal treatment of pain associated with hip arthroplasty. This multicenter, multiple-dose, double-blind, parallel-group study compared the opioid-sparing effects, analgesic efficacy, and safety of 20- and 40-mg doses of valdecoxib twice daily with placebo in patients receiving morphine by patient-controlled analgesia after hip arthroplasty. Study medication was first administered 1 to 3 hours preoperatively. The total amount of morphine administered, pain intensity, and patient's global evaluation of study medication were assessed over a period of 48 hours. Patients receiving 20 or 40 mg valdecoxib twice daily required on average 40% less morphine than those receiving placebo after hip arthroplasty. Pain intensity levels and patient satisfaction were significantly improved in both valdecoxib groups compared with placebo. Valdecoxib and placebo were equally well tolerated. Pre- and postoperative administration of valdecoxib reduces the amount of morphine required for postoperative pain relief and provides greater analgesic efficacy compared with morphine alone. Thus, valdecoxib has significant clinical utility for acute pain management in orthopedic surgery patients.
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PMID:Valdecoxib, a COX-2-specific inhibitor, is an efficacious, opioid-sparing analgesic in patients undergoing hip arthroplasty. 1178 19

Inhibition of the cyclooxygenase (COX)-2 enzyme has been shown previously to reduce pain and inflammation. Valdecoxib is a new highly selective COX-2 inhibitor with a rapid onset of action and significant analgesic properties. This study compared the analgesic efficacy of valdecoxib and rofecoxib in treating postoperative pain in patients undergoing oral surgery. This randomized, double-blind, placebo-controlled study compared the efficacy of 40 mg valdecoxib with that of 50 mg rofecoxib and placebo. Efficacy was assessed by the onset of analgesia, pain intensity levels, and pain relief over 24 hours, time-weighted sum of total pain, sum of pain intensity difference, the percentage of patients requiring rescue medication and experiencing regimen failure, and patients' global evaluation. Patients receiving valdecoxib experienced a significantly quicker onset of analgesia, significantly improved pain relief, and lower pain intensity compared with patients receiving rofecoxib and greater satisfaction with their study medication after a single dose. Valdecoxib also demonstrated efficacy that was superior to that of rofecoxib with respect to the percentage of patients requiring rescue medication or experiencing regimen failure (p < or =.05). Valdecoxib, rofecoxib, and placebo were equally well tolerated. This study demonstrates that valdecoxib provides significantly greater analgesic efficacy than rofecoxib in the management of pain after oral surgery.
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PMID:Valdecoxib is more efficacious than rofecoxib in relieving pain associated with oral surgery. 1189 23

Although its inclusion in medical research is relatively recent and its interpretation is often variable, quality of life is increasingly being recognized as one of the most important parameters to be measured in the evaluation of medical therapies, including those for pain management. Pain, when it is not effectively treated and relieved, has a detrimental effect on all aspects of quality of life. This negative impact has been found to span every age and every type and source of pain in which it has been studied. Effective analgesic therapy has been shown to improve quality of life by relieving pain. Opioid analgesics, cyclooxygenase (COX)-2 inhibitors (or coxibs), and several adjuvant analgesics for neuropathic pain have been demonstrated to significantly improve quality-of-life scores in patients with pain. Coxibs provide effective, well-tolerated analgesia without some of the issues faced with opioids-benefits that should translate into improved quality of life. Recent studies have demonstrated that the COX-2 inhibitor rofecoxib significantly improves quality of life in patients with osteoarthritis and chronic, lower back pain. Quality-of-life measurements, especially symptom distress scales, can also be used as sensitive means of differentiating one agent from another in the same class. In future pharmacotherapeutic research, quality of life should be included as an outcome domain as are the traditionally measured variables of efficacy and safety. In particular, future studies of coxibs should include symptom distress scores as important quality-of-life measurements, to identify meaningful differences between this new class of analgesics and nonselective nonsteroidal anti-inflammatory drugs.
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PMID:The impact of pain management on quality of life. 1220 86

Flunixin (FLX) and ketoprofen (KET) are potent nonsteroidal anti-inflammatory drugs (NSAIDs) used to alleviate pain and decrease inflammation. These drugs block access of arachidonic acid to its binding site on the cyclooxygenase enzyme, thus preventing conversion to thromboxane A2 and subsequent degradation to thromboxane B2 (TBX). Consequently, plasma TBX may be used to estimate duration of NSAID action. Sixteen adult mallard ducks (Anas platyrhynchos) were randomly assigned to three treatment groups: control (n = 4), FLX 5 mg/kg (n = 6), or KET 5 mg/kg (n = 6). Blood samples were taken 1 hr prior to and just before (0 hr) injection and 0.25, 0.5, 1, 2, 4, 6, 12, 24, 36, and 48 hr after injection. Plasma samples were analyzed for corticosterone and TBX. The feces were tested for the presence of hemoglobin and the ducks were euthanized for complete necropsy at the end of the study. Samples of muscle, kidney, liver, proventriculus, and intestine were taken for histologic analysis. Thromboxane was suppressed significantly in all birds following administration of either FLX or KET for 4 hr and decreased for approximately 12 hr compared with baseline samples (-1 and 0 hr). In the control group, TBX gradually declined over time. None of the ducks showed evidence of gastrointestinal bleeding, but the FLX group had muscle necrosis present at injection sites. FLX and KET likely exert pharmacological effects for at least 12 h. Although degree of TBX inhibition cannot be correlated absolutely with degree of analgesia or anti-inflammatory effects, it is possible that these effects are present during this time. This work suggests that FLX and KET can potentially be used as anti-inflammatory and analgesic agents in waterfowl. However, because of muscle necrosis at the injection site, we do not recommend parenteral use of FLX in ducks.
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PMID:Pharmacodynamics of flunixin and ketoprofen in mallard ducks (Anas platyrhynchos). 1279 Apr 25

This article reviews the gastrointestinal manifestations of traditional nonsteroidal anti-inflammatory drugs (NSAIDs) and the improved gastrointestinal safety profile of cyclooxygenase selective (COX)-2 inhibitors. By inhibiting the COX enzyme, NSAIDs provide effective analgesia and suppress inflammation in a variety of conditions. Most NSAIDs (nonselective or traditional) not only inhibit prostaglandins at sites of inflammation but also inhibit prostaglandins that have important normal functions in other parts of the body. This may be harmful when normal gastrointestinal mucosal function is impaired and mucosal damage occurs. Although such damage is often trivial and usually not symptomatic, gastrointestinal ulceration may produce pain and, more ominously, lead to bleeding, perforation, or obstruction. A new approach to the gastrointestinal complications of NSAIDs became feasible with the discovery of two isoforms of COX, COX-1 and COX-2, with COX-1 expressed mainly in the gastrointestinal tract. The development of NSAIDs that preferentially inhibit COX-2 offers the promise of relieving pain and inflammation without the side effects attendant to COX-1 blockade. In prospective studies evaluating gastrointestinal ulceration with COX-2-specific NSAIDs, rates of endoscopic ulceration have been equivalent to those with placebo and much lower than those with nonselective NSAIDs. In the recently released studies of gastrointestinal outcomes (perforated, painful, or bleeding ulcers), incidence of clinically relevant ulceration with COX-2 NSAIDs is much lower than that of traditional NSAIDs.
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PMID:The role of cyclooxygenase selective inhibitors in the gastrointestinal tract. 1460 52

Non-steroidal antiinflammatory drugs (NSAIDs) are known to induce analgesia mainly via inhibition of cyclooxygenase (COX). Although the inhibition of COX in the periphery is commonly accepted as the primary mechanism, experimental and clinical data suggest a potential role for spinal COX-inhibition to produce antinociception and reduce hypersensitivity. We used an experimental model of electrically evoked pain and hyperalgesia in human skin to determine the time course of central analgesic and antihyperalgesic effects of intravenous parecoxib and paracetamol (acetaminophen). Fourteen subjects were enrolled in this randomized, double blind, and placebo controlled cross-over study. In three sessions, separated by 2-week wash-out periods, the subjects received intravenous infusions of 40 mg parecoxib, 1000 mg paracetamol, or placebo. The magnitude of pain and areas of pinprick-hyperalgesia and touch evoked allodynia were repeatedly assessed before, and for 150 min after the infusion. While pain ratings were not affected, parecoxib as well as paracetamol significantly reduced the areas of secondary hyperalgesia to pinprick and touch. In conclusion, our results provide clear experimental evidence for the existence of central antihyperalgesia induced by intravenous infusion of two COX inhibitors, parecoxib and paracetamol. Since the electrical current directly stimulated the axons, peripheral effects of the COX inhibitors on nociceptive nerve endings cannot account for the reduction of hyperalgesia. Thus, besides its well-known effects on inflamed peripheral tissues, inhibition of central COX provides an important mechanism of NSAID-mediated antihyperalgesia in humans.
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PMID:The cyclooxygenase isozyme inhibitors parecoxib and paracetamol reduce central hyperalgesia in humans. 1510 18

Several lines of evidence have accumulated that release of excitatory amino acids, nitric oxide and prostaglandin E2 (PGE2) play a critical role in the development of peripheral tactile and thermal hypersensitivity in chronic inflammatory pain models. Synthesis of PGE2 is controlled by cyclooxygenase (COX), either the COX-1 or COX-2 isoform. COX-2 plays a central role in the inflammatory reactions. The relationship between central sensitization of a complete Freund's adjuvant (CFA) induced inflammation and expressions of COX-2 were assessed in a rat model of CFA injection induced inflammation. Moreover, the time course of analgesia and spinal COX-2 expression following intrathecal (IT) injection with a nonspecific COX inhibitor (ketorolac) and COX-2 inhibitor (celecoxib) were determined using Western blot and immunohistochemistry. COX-2 protein was slightly increased in the lumbosacral spinal cord at 24 h following subcutaneous injection of CFA in the plantar surface of the left hindpaw (p > 0.05). COX-1 was not detected in normal and CFA injection rats. Surprisingly, IT ketorolac or celecoxib significantly increased spinal COX-2 levels at 1 h post-IT injection (p < 0.05) both in inflamed and non-inflamed rats. Then, spinal COX-2 levels declined at 3 and 6 h post-IT injection. These results provide strong in vivo evidence that COX-2 activity but not level may play a central role in the Freund's adjuvant-induced inflammation. However, spinal COX-2 level was upregulated following IT ketorolac and celecoxib injection. These data implies that suppression of PGE2 activity may induce the expression of spinal COX-2 in Freund's adjuvant-induced pain model. Our study concludes that IT administration of COX-2 inhibitor or nonspecific COX inhibitor is associated with significant short-term increase in spinal COX-2 expression.
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PMID:Nonsteroidal anti-inflammatory drugs increase expression of inducible COX-2 isoform of cyclooxygenase in spinal cord of rats with adjuvant induced inflammation. 1519 28

Non-steroidal anti-inflammatory drugs (NSAIDs) and opioids are the most commonly used analgesics in the management of acute and chronic pain. Combined use of NSAIDs and opioids has been indicated for achieving better analgesia with reduced side effects. The present study was aimed at evaluating the combination of different NSAIDs, which inhibit cyclooxygenase (COX) enzymes and tramadol against acetic acid-induced writhing in mice. The expected beneficial effect of combination regimen was analyzed by isobolographic analysis. The oral and intrathecally administered tramadol, a mu-opioid and naproxen, a nonselective COX inhibitor produced dose-dependent antinociception, however, rofecoxib, a selective COX-2 inhibitor lacked analgesic efficacy in writhing test. Isobolographic analysis showed synergistic or supra-additive interactions for the combinations of naproxen and tramadol after oral and intrathecal administration. However, similar interaction was not observed when tramadol was combined with rofecoxib. Pretreatment with naloxone partially reversed the antinociceptive effect of tramadol per se and its combination with naproxen without modifying the per se effect of NSAID. The results demonstrated marked synergistic interaction between naproxen and tramadol and such interaction involved opioid as well as non-opioid mechanisms of tramadol and inhibition of COX-1 but not COX-2 by naproxen.
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PMID:Isobolographic analysis of interaction between cyclooxygenase inhibitors and tramadol in acetic acid-induced writhing in mice. 1527 89

The present study provides an important implication for the management of chronic neuropathic pain, focusing on prostaglandin (PG) and nitric oxide (NO) in the spinal cord. To determine if spinally administered cyclooxygenase (COX) inhibitor or nitric oxide synthase (NOS) inhibitor had preemptive analgesia on thermal hypersensitivity induced by chronic constrictive nerve injury, Sprague-Dawley rats were chronically implanted with an intrathecal (i.t.) catheter. The left sciatic nerve was loosely ligated with 2-mm polyethylene tubing to produce painful mononeuropathy. Animals received tenoxicam (7.5, 15 or 30 micromol/10 microl, i.t.), NS-398 (15 or 30 micromol), or L-NAME (30, 150 or 300 micromol) immediately before the nerve injury, followed by daily injection extending into the four postoperative days. The hindpaw was immersed into a hot (42 degrees C, 44 degrees C and 46 degrees C) or cold (10 degrees C) water bath. The paw immersion test revealed significant thermal hyperalgesia and allodynia 5 day after nerve injury in vehicle control animals. Tenoxicam (7.5, 15 or 30 micromol) or L-NAME (30, 150 or 300 micromol) dose-dependently attenuated hyperalgesia and allodynia. Equimolar dose of NS-398 (15 or 30 micromol) also diminished these nociceptive behaviors. Higher dose of either drug primarily produced longer duration of inhibition. The inhibitory effect of tenoxicam (30 micromol) on hyperalgesia was more effective than that of an equimolar dose of NS-398 or L-NAME. These results demonstrated that intrathecally administered COX inhibitor or NOS inhibitor provides preemptive analgesia on thermal hypersensitivity following chronic constrictive nerve injury in rats.
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PMID:Preemptive effects of intrathecal cyclooxygenase inhibitor or nitric oxide synthase inhibitor on thermal hypersensitivity following peripheral nerve injury. 1536 58

Nonsteroidal anti-inflammatory drugs produce their analgesic and adverse effects through interaction with cyclooxygenase in a variety of tissues. The authors evaluated the therapeutic potential of administering a sustained-release formulation of flurbiprofen into a surgical wound following oral surgery to produce analgesia at the site of injury while minimizing exposure to potential targets for toxicity. Subjects (N = 98) received 1 of 8 treatments: flurbiprofen in a microparticle formulation in doses of 3.125 mg, 6.25 mg, 12.5 mg, 25 mg, or 50 mg; PO flurbiprofen 25 mg or 50 mg; or placebo. The flurbiprofen microparticle formulation or matching placebo was placed into the extraction sites at the end of surgery (removal of 2 lower impacted third molars). The sum of the pain visual analog scale over the 6-hour observation period demonstrated significantly less pain (P < .05) for flurbiprofen microparticle in comparison with placebo. Fewer subjects remedicated in the flurbiprofen microparticle drug groups, primarily for the 12.5-mg and higher doses. The incidence of adverse effects and local complications did not differ across groups. These data suggest that direct administration of flurbiprofen in a microparticle formulation at a site of tissue injury delays the onset and lowers the intensity of postoperative pain at lower doses than usually administered orally.
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PMID:Analgesic effect of sustained-release flurbiprofen administered at the site of tissue injury in the oral surgery model. 1554 14


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