Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0344307 (analgesia)
 28,200 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Despite the widespread use of radiotherapy to treat painful bone metastases, the mechanism underlying the analgesic effect of low dose ionizing radiation is unknown. Bone cancer pain is mostly associated with an inflammatory response dominated by local activation of osteoclasts and by astrogliosis in the spinal cord. We determined the effects of a 6 Gy irradiation given focally on osteolytic sarcoma cells inoculated in humeri of mice. Pain behavior was assessed using the rota-rod and the grip force test. Seven days post-irradiation (day 17 post-tumor implantation) the performance of mice markedly improved on the rotarod (non-irradiated, 67+/-16s vs irradiated, 223 +/- 22 s; P = 0.0005), and the grip force test (non-irradiated, 34 +/- 4 g vs irradiated, 55 +/- 2 g; P = 0.001). This improvement was similar to the analgesia achieved with 30 mg/kg of the cyclooxygenase (COX) inhibitor ketorolac (Rota-rod, 67 +/- 16 s vs 178 +/- 35 s; P = 0.01: grip force test, 34 +/- 4 g, vs 60 +/- 5 g; P = 0.003). Following irradiation, the tumor mass and the number of osteoclasts did not decrease while the expression of two pro-inflammatory cytokines (monocyte chemoattractant protein (MCP)-1 and tumor necrosis factor (TNF)-alpha) increased. Tumor irradiation led to clear differences in the spinal cord. These include a decrease in glial activity (astrocytes and microglial cells) as well as pain mediators such as dynorphin, COX-2 and chemotactic cytokine receptor (CCR2). We conclude that the analgesic effect of low dose irradiation of bone cancer is associated with the alteration of nociceptive transmission in the central nervous system.
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PMID:The analgesic effect of low dose focal irradiation in a mouse model of bone cancer is associated with spinal changes in neuro-mediators of nociception. 1636 Feb 79

This review summarizes and critically appraises important and clinically relevant publications dealing with postoperative pain therapy. Several consequences can be drawn from these studies: i) women anticipate postoperative pain more realistically and it occurs more often than in man; however, pain intensity and analgesic consumption are not different; ii) placebos elicit psychological phenomena (e. g. expectation) that trigger neurobiological processes (e. g. activation of endogenous opioid system); iii) COX-2 inhibitors increase the risk for thromboembolic complications (e. g. myocardial infarction, apoplex, pulmonary embolism) and perioperative mortality in patients undergoing aortocoronary bypass surgery; iv) NSAID as supplement to postoperative PCIA with opioids reduce the risk for PONV and sedation; v) preoperative administration of gabapentin reduces preoperative anxiety and postoperative pain; vi) epidural catheters situated at the site of major spinal surgery are promising approach to provide efficient postoperative analgesia; vii) in the literature contradictory results have been reported regarding the effect of perioperative acupuncture on intra- and postoperative consumption of anesthetics or analgesics; acupuncture appears to decrease the incidence of PONV, but no reduction in the postoperative use of antiemetic agents has not been shown yet; viii) laparoscopic versus open colectomy in patients with colon carcinoma results in prolongation of surgery, reduction of postoperative pain and analgesics, earlier mobilization and a reduced hospital stay, if conventional systemic opioid-based pain therapy was used postoperatively.
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PMID:[New aspects in postoperative pain therapy]. 1655 49

The COX-inhibiting nitric oxide donors (CINODs) are a new class of agents designed for the treatment of pain and inflammation. CINODs have a multi-pathway mechanism of action that involves COX inhibition and nitric oxide donation. The anti-inflammatory and analgesic effects of COX inhibition are reinforced through inhibition of caspase-1 regulated cytokine production, while nitric oxide donation provides multiorgan protection. Whereas both conventional nonsteroidal anti-inflammatory drugs (NSAIDs) and COX-2-selective NSAIDs are associated with a variety of adverse effects on the renal system, such as hypertension and edema, CINODs may offer an improved renal safety profile. These agents are devoid of hypertensive effects in animal models and their mechanism of action suggests that they may not cause edema. CINODs also have other renal-sparing effects, being better tolerated than NSAIDs in models of kidney failure. CINODs have been shown to prevent platelet activation in vitro and exhibit anti-thrombotic activity in vivo. In animal models of ischemia/reperfusion, CINODs treatment results in improved recovery of heart contractility and reduced left ventricular end-diastolic pressure, in contrast to the effects of aspirin. The combination of improved analgesia, reduced gastrointestinal toxicity and cardiorenal protection has been established in animal models, and early clinical results suggest a favourable gastrointestinal safety profile in humans. The potential for CINODs to provide cardiorenal protection in humans is currently being investigated.
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PMID:COX-inhibiting nitric oxide donors (CINODs): potential benefits on cardiovascular and renal function. 1661 Oct 49

Postoperative pain requires treatment not only to provide comfort to patients but also to improve postoperative outcome. Anti-inflammatory compounds are an important component of multimodal analgesia in the postoperative period. The newer cyclooxygenase (COX)-2 inhibitors are as effective as classical nonsteroidal anti-inflammatory drugs (NSAIDs) in this setting. However, COX-2 inhibitors offer a number of advantages over NSAIDs when used to treat postoperative pain. These include a reduced incidence of gastrointestinal ulceration and no inhibitory effect on platelet function and thereby a reduced risk of blood loss. Other benefits are less impairment of bone healing and no induction of bronchospasm in patients with aspirin-sensitive asthma. Increased cardiovascular thromboembolic events by COX-2 inhibitors have been reported after coronary artery bypass graft surgery only, but in general, surgery studies the incidence of such complications was comparable to placebo. Overall, COX-2 inhibitors offer a number of advantages over classical NSAIDs in the postoperative pain setting, but require the same caution with regard to renal effects.
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PMID:The role of COX-2 inhibitors in the treatment of postoperative pain. 1678 36

Cyclooxygenase inhibitors reduce inflammation and hyperalgesia by decreasing prostaglandin E2 production. Traditional NSAIDs (inhibiting both COX-1 and 2) though ubiquitous in peri-operative pain practice, have well-known gastrointestinal (GI), cardiovascular and other risks. This article systematically addresses the main efficacy and safety issues pertaining to NSAID and selective COX-2 inhibitors (coxibs) use, focusing on the acute pain context, particularly post-operative pain management. NSAIDs and coxibs are of proven analgesic efficacy in post-operative pain control, and their opioid-sparing role in multimodal analgesia, leads to significantly reduced opioid related side effects. Although GI risk is regarded as less of an issue in short-term therapy, in patients with a past history of peptic ulceration who are denied NSAIDs, coxibs may be considered a suitable alternative. In the peri-operative setting, coxibs confer an additional advantage over NSAIDs by preserving the platelet thromboxane production and clotting. Cardiovascular safety has been assessed for the parenteral parecoxib and its active moiety valdecoxib, and was found to be satisfactory in major non-cardiac surgery, but increased thromboembolic complications occurred in coronary artery bypass surgery leading to contra-indication for this type of surgery. Coxibs and NSAIDs have similar renal effects and caution or avoidance is required with renal disease or reduced peri-operative renal perfusion. Coxibs may be safer in aspirin-sensitive asthmatics. Bone healing effects remain controversial, but only a few days therapy appears to be safe.
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PMID:Selective cyclooxygenase inhibition: its role in pain and anaesthesia. 1683 62

Studies of hypersensitivity to mechanical stimuli after incisional surgery suggest that cyclooxygenase (COX)-1, but not COX-2, in the spinal cord participates in postoperative pain. In the current study, we sought to determine the role of COX isoenzymes after laparotomy, examining spontaneous exploratory behavior rather than withdrawal reflexes. Adult male Sprague-Dawley rats underwent subcostal laparotomy surgery under isoflurane anesthesia or received anesthesia without surgery. Exploratory locomotor activity was measured on the first postoperative day after intrathecal injection of dimethyl sulfoxide (vehicle) or COX-1 (SC-560) or COX-2 (NS-398) inhibitors. Laparotomy reduced ambulation, rearing, and rapid small movements (stereotypy) similarly in animals without intrathecal catheters and those receiving intrathecal vehicle control. SC-560 produced a dose-related return to normal exploratory behavior with complete return at doses of 20 mug and larger. In contrast, NS-398 in doses up to 50 mug failed to increase exploratory behavior. These data with exploratory behavior and laparotomy agree with studies with reflexive withdrawal responses after incisional surgery and indicate that COX-1 inhibition reduces pain responses after surgery. Spinal COX-1 inhibition completely restores exploratory activity, including rearing behavior that stretches the abdominal muscles. These data suggest that targeting COX-1 in the spinal cord may produce postoperative analgesia.
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PMID:Intrathecal administration of a cylcooxygenase-1, but not a cyclooxygenase-2 inhibitor, reverses the effects of laparotomy on exploratory activity in rats. 1693 82

Nonsteroidal anti-inflammatory drugs (NSAIDs) are currently the most widely used class of therapeutic agents. By inhibiting cyclooxygenase (COX) and reducing gastrointestinal prostaglandins, they provide effective analgesia and suppress inflammation in a variety of conditions. However, through the same mechanism of COX inhibition, they also cause significant gastrointestinal toxicity. One of the most common methods to reduce NSAID-induced gastrointestinal toxicity has been to co-prescribe prophylactic therapies such as acid-reducing agents or the synthetic prostaglandin analogue, misoprostol. More recently safer NSAIDs, such as the COX-2 specific NSAIDs or the nitric oxide-releasing NSAIDs, have been developed or are currently in development. This article reviews mechanisms of NSAID-induced gastrointestinal toxicity. Also reviewed are data on the gastrointestinal consequences of the prophylatic co-therapies, COX-2 specific NSAIDs and nitric oxide-releasing NSAIDs.
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PMID:Nonsteroidal anti-inflammatory drug gastrointestinal toxicity. 1702 93

The development of COX-2 selective inhibitors has opened a new era of clinical investigation in NSAIDs. Discussion of the established concepts of inflammation and therapeutical uses of these drugs has changed the rationale for its clinical use and therapeutic labeling of these drugs. A comprehensive discussion across basic science and clinical areas involved in each of these concepts is presented. This led to a remarkable re-evaluation of our insights on their traditionally proposed mechanisms of analgesia, their side-effects, and the clinical indication of NSAIDs as "over the counter" pain killers. This may shift physicians toward a more rational use of this drug class.
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PMID:A critical appraisal of COX-2 selective inhibition and analgesia: how good so far? 1714 69

A follow-up of 180 women was carried out. The patients having endured different gynecological operations (laparoscopy, laparohysterectomy, etc.) were divided into two main groups: half of them were treated with Dynastat (new selective COX-2 inhibitor) and the others were treated with Profenid (conventional nonsteroidal anti-inflammatory drug). The groups were compared by the quality of the achieved analgesia and appeared side effects, especially postoperative nausea and vomiting. These parameters were assessed by both medics and patients. In conclusion we accept that the new COX-2 selective inhibitor Dynastat does not have advantages over traditional nonsteroidal anti-inflammatory drug as Profenid especially for postoperative nausea and vomiting and quality of analgesia.
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PMID:[Usage of the new parenteral selective cox-2 inhibitor dynastat in the gynecologic practice]. 1716 90

Nonsteroidal anti-inflammatory drugs (NSAIDs) inhibit cyclooxygenases (COX) and are widely used for post-trauma musculoskeletal analgesia. In animal models, NSAIDs have been reported to delay fracture healing and cause non-union, possibly due to the drug-induced inhibition of osteoblast recruitment and differentiation. To further investigate the cellular effects of these drugs in the context of bone healing, we examined the effects of COX-1 inhibitor indomethacin and COX-2 inhibitors, parecoxib and NS398 on osteoclast and osteoblast differentiation and activity in vitro. We discovered that all tested COX-inhibitors significantly inhibited osteoclast differentiation, by 93%, 94% and 74% of control for 100 microM indomethacin, 100 microM parecoxib and 3 microM NS398, respectively. Furthermore, inhibition of COX-2 reduced also the resorption activity of mature osteoclasts. All tested COX-inhibitors also significantly inhibited osteoblast differentiation from human mesenchymal stem cells. Simultaneously, the number of adipocytes was significantly increased. The adipocyte covered areas in the cultures with 1 microM indomethacin, 1 microM parecoxib and 3 microM NS398 were 9%, 29% and 24%, respectively, as compared with 6% in the control group. This data suggests that COX-2 inhibition disturbs bone remodelling by inhibiting osteoclast differentiation and diverting stem cell differentiation towards adipocyte lineage instead of osteoblast lineage. In conclusion, our results further suggest cautious use of COX-2 inhibitors after osseous trauma.
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PMID:Inhibition of cyclooxygenase-2 down-regulates osteoclast and osteoblast differentiation and favours adipocyte formation in vitro. 1763 97


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