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)

Paediatric patients quite often have to undergo painful or stressful procedures, e. g. blood sampling, dressing of wounds or removal of a drainage. The key problem is to decide if a child has pain or if there are other reasons for crying. Establishing a high standard in an institution requires regular evaluation and documentation of pain scores. For many clinical situations, clear and functioning concepts exist - we just have to use them. Unanswered questions are the evaluation of pain in small children, the side-effects of opioids, surgery involving the airways and the risk-benefit-ratio of certain techniques. Pain therapy after tonsillectomy is still troublesome: relevant postoperative pain occurs. Local infiltration of the tonsillar bed has no pre-emptive effect and only a minimal impact on the postoperative pain. Management relies on opioids, steroids and non-opioids. Non-steroidal anti-inflammatory drugs should not be used because of an increased risk of bleeding. Promising data have been reported on COX-2-blockers, but experience in children is still limited. Pain management after circumcision is relatively easy to perform. A conduction block with a long-acting local anaesthetic combined with one dose of a non-steroidal anti-inflammatory drug provides sufficient analgesia in over (2/3) of patients. Today, penile block is the standard of care and complications only rarely occur. However, despite successful pain prevention, circumcision remains a stressful procedure for the small patients. Pain treatment per se is not sufficient to relieve all the suffering connected with surgery in children. The concept of balanced analgesia is successful under many circumstances, but continuous efforts are needed to improve the management for difficult situations, e. g. tonsillectomy.
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PMID:[Pain treatment in neonates, infants and children--is the current treatment sufficient?]. 1533 28

Postoperative pain is one of the most common forms of acute pain. Optimal pain management decreases the stress response to surgery, reduces complications, improves recovery time, and results in improved economic and quality-of-life outcomes. A preoperative, multimodal approach to postoperative analgesia can be achieved through a combination of therapies that continue beyond the immediate perioperative time frame. This multimodal approach provides superior analgesia with opioid-sparing effects and reduced opioid-related adverse events. Although the use of nonspecific nonsteroidal antiinflammatory drugs in a surgical setting has been limited owing to concerns of renal and gastrointestinal complications as well as platelet dysfunction, cyclooxygenase (COX)-2-specific inhibitors appear to be safe and effective alone and in combination with opioids for a variety of surgical procedures. The COX-2-specific inhibitors may have an important role in extending the use of balanced, multimodal analgesia to a broad surgical population, thus ultimately improving patient outcomes after surgery.
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PMID:Making progress in the management of postoperative pain: a review of the cyclooxygenase 2-specific inhibitors. 1558 40

Systemic administration of analgesics is still the most widely used method for postoperative pain therapy. In the concept of balanced or multimodal analgesia non-steroidal anti-inflammatory drugs (NSAIDs) play an important role besides opioids. Their analgesic effect is based on a diminished prostaglandin synthesis by inhibition of the cyclooxygenase (COX) enzyme in the arachidonic acid metabolism. The discovery of at least two COX isoenzymes led to the development of selective COX-2 inhibitors that were hypothesized to have an improved risk-benefit-ratio compared with conventional NSAIDs. In this context the analgesic efficacy and adverse effects of selective COX-2 inhibitors for postoperative pain therapy were evaluated by reviewing the pertinent literature.
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PMID:[Selective cyclooxygenase-2 inhibitors for postoperative pain therapy. Analgesic efficacy and adverse effects]. 1559 62

Paracetamol produces analgesia in the mouse writhing test through a central action which is paralleled by a reduction in brain PGE(2) concentrations. In contrast, diclofenac has a peripheral analgesic action in this test. Paracetamol-induced hypothermia is also accompanied by a reduction in brain PGE(2) concentrations in C57/Bl6 mice. This hypothermic effect of paracetamol was reduced in COX-1 but not in COX-2 gene-deleted mice. These results support the view that analgesia and hypothermia due to paracetamol are mediated by inhibition of a third COX isoenzyme (designated COX-3). In cultured mouse macrophages, COX-2 is induced by treatment with LPS or with high concentrations of diclofenac. Diclofenac-induced COX-2 is inhibited with low concentrations of paracetamol, whereas LPS-induced COX-2 is insensitive to paracetamol inhibition. The mechanisms of induction and possibly the functions of these two COX-2 enzymes are also different.
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PMID:COX-3 and the mechanism of action of paracetamol/acetaminophen. 1562 90

To assess the impact of individualized medication effectiveness tests (IMETs, or n-of-1 trials), on patients' short-term decision making about medications for chronic pain. Survey evaluation of patients undergoing a double-blind, crossover comparison of drug versus placebo, drug versus drug, or drug versus drug combination using paracetamol and ibuprofen in 3 pairs of treatment periods, randomized within pairs. General practice patients (supplemented by a few from 2 tertiary pain clinics) with either chronic pain (> or =3 months), or osteoarthritis (with pain for > or =1 month) severe enough to warrant consideration of long-term nonsteroidal antiinflammatory drug (NSAID) use but for whom there was doubt about the efficacy of NSAID or alternative. Pain and stiffness in sites nominated by the patient, global pain, use of escape analgesia, and side effects. Of 116 IMETs started, 71 were completed. Drug management changed for 46 of 71 (65%). The most common change was to add paracetamol or to substitute the NSAID or COX-2 inhibitor with paracetamol (25 of 71 patients and 54% of changes). Of the 37 who were using NSAIDs or COX-2 inhibitors before the IMET, 12 (32%) ceased these afterward. Paracetamol was as effective or more effective than ibuprofen in 37 (68%) of the 54 IMETs directly comparing these drugs. IMETs provide useful information for clinical decisions. Paracetamol continues to be useful for patients with chronic pain whose optimal drug choice is in doubt. Our results provide a new (individual) perspective on the well-known recommendation for paracetamol as first-line treatment for chronic pain and demonstrate that it is feasible to provide IMETs nationally by mail and telephone.
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PMID:Do individualized medication effectiveness tests (n-of-1 trials) change clinical decisions about which drugs to use for osteoarthritis and chronic pain? 1566 96

The post-operative pain state results from a barrage of primary afferent inputs exposed to products of tissue damage such as bradykinin and prostaglandins and the central sensitization by the continuing inputs. This provides the rationale for preemptive analgesia, whereby the blockade of primary afferent inputs prior to injury may result in a reduction of post-operative pain. 2-(10,11-dihydro-10-oxo-dibenzo[b,f]thiepin-2-yl) propionic acid (zaltoprofen) is a unique compound that inhibits cyclooxygenase (COX) and exhibits anti-bradykinin activity. The present study evaluated the preemptive analgesic effect of zaltoprofen in a post-operative pain model produced by plantar incision. When orally, but no intrathecally, administered 30 min prior to incision, zaltoprofen significantly increased the withdrawal threshold 2 h and 1-3 days after incision at 10 mg/kg. While the bradykinin B1 antagonist des-Arg10-HOE-140, the selective COX-1 inhibitor SC-560, and the selective COX-2 inhibitor celecoxib did not affect post-operative pain, the B2 antagonist HOE-140 dose-dependently relieved the post-operative pain at 2-200 microg/kg with a time course similar to that of zaltoprofen. The B2 receptor mRNA was expressed in the hindpaw and the expression did not change before and 24 h after surgery. These results suggest that zaltoprofen produces the preemptive analgesic effect peripherally by blocking the B2 pathway.
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PMID:Preemptive analgesia by zaltoprofen that inhibits bradykinin action and cyclooxygenase in a post-operative pain model. 1574 Aug 5

The mechanism by which COX inhibitors exert their analgesic effect is well established. However, data show no direct correlation between drug concentrations in plasma and the analgesic or adverse effects in chronic inflammatory conditions. This represents a major problem in the development of COX inhibitors, since it is difficult to predict the appropriate dosing regimen for the treatment of chronic inflammatory pain, based upon information from pre-clinical studies and eventually early clinical studies. The factors that determine response in inflammatory pain must be understood in order to make predictions about the time course of the analgesic effect. In this review the determinants of drug response and their variability will be discussed: physicochemical properties, pharmacokinetics (PK), pathophysiology and disease progression. From a mechanistic point of view, endogenous mediators of inflammation might be used as a biomarker for the analgesic effect and safety assessment. Such a biomarker can be an intermediate step between drug exposure and response. In addition, its concentration-effect relationship could be characterized by pharmacokinetic-pharmacodynamic (PK/PD) modelling. Indeed, recent investigations have shown that COX-2 inhibition, as determined by modelling of prostaglandin E2 (PGE2) levels in the whole blood assay in vitro can be used as a marker to predict drug effects (analgesia) in humans. A model-derived parameter, IC80, (total and unbound) was found to correlate directly with the analgesic plasma concentration of different COX inhibitors varying in enzyme selectivity. These findings indicate that PGE2 and thromboxane B2 inhibition can be used to predict and select efficacious doses in humans.
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PMID:Pharmacokinetic-pharmacodynamic correlations and biomarkers in the development of COX-2 inhibitors. 1585 83

This study was designed to test the hypothesis whether preemptive administration of rofecoxib, a novel selective COX-2 inhibitor, can prolong intraarticular bupivacaine analgesia after arthroscopic knee surgery. Sixty-two patients were randomly assigned to one of the three groups. Group 1 (n=21) was administered oral rofecoxib 50 mg 1 h before surgery plus intraarticular 0.5 % bupivacaine 20 ml postoperatively. Group 2 (n=21) was administered the same dose of bupivacaine. Group 3 (n=20) was administered saline 20 ml intraarticularly after surgery. Pain scores (VAS) were assessed at 30 min, 1, 2, 4, 6, 12 and 24 h postoperatively. Analgesia duration, analgesic (tramadol and tenoxicam) requirements, and adverse effects were recorded postoperatively for 24 h. Pain scores were significantly lower in the Group 1 at all time points (p<0.05, p<0.001) and were significantly lower in the Group 2 at 30 min (p<0.001), 1 and 4 h (p<0.05) compared to the Group 3. Pain scores were significantly lower in the Group 1 compared to the Group 2 during the first 4 h after surgery (p<0.05, p<0.001). Analgesia duration was longer in Group 1 than Group 2 or 3 (743.0 +/- 480.5 min versus 262.4 +/- 292.2 min and 17.0 +/- 12.1 min; p<0.05, p<0.001 respectively), and in Group 2 than Group 3 (p<0.05). Tramadol requirements were significantly less in Group 1 than Group 2 and 3 (4.8 +/- 15.0 mg versus 40.5 +/- 43.6 mg and 67.5 +/- 24.5 mg; p<0.05, p<0.001 respectively), and in Group 2 than Group 3 (p<0.05). There were no significant differences among the groups regarding the tenoxicam requirements and adverse effects. In conclusion, the combination of oral rofecoxib administered preemptively and intraarticular bupivacaine administered postoperatively provided a significant analgesic benefit and decreased the opioid requirements after arthroscopic knee surgery, when compared to bupivacaine alone or saline.
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PMID:Preemptive oral rofecoxib plus postoperative intraarticular bupivacaine for pain relief after arthroscopic knee surgery. 1597 92

Pharmacologists have generally been prejudiced against prostanoids, uncritically accepting their suppression as desirable therapy, especially for 'quick-fix' analgesia. This myopic perception for a long time ignored (a) the essentiality of prostanoid precursors in nutrition, (b) the physiological protective functions of natural prostaglandins (PGs) (vasculature, stomach, kidney), (c) resolution of inflammation after the expression of COX-2 and (d) increasing therapeutic use of either synthetic PGs (for erectile dysfunction, ophthalmic disorders, inducing parturition, etc) or their natural precursors, e.g., omega3-rich polyunsaturated oils, to treat arthritis. Experimental studies in rats have indicated that prostaglandins (E series) are (i) useful, perhaps auto-regulators of established immunoreactivity and (ii) able to amplify (or even induce) anti-inflammatory activity with other agents. Furthermore, anti-prostanoid therapy (APT) can be arthritigenic!!, interfering with the acquisition of tolerance to some arthritigens. For patients with rheumatoid arthritis this additional side-effect of APT, barely recognised to date, may actually perpetuate their arthritis by impairing prostanoid-mediated remission processes. Hopefully, recent adverse publicity about COX-2 inhibitory drugs might stimulate serious re-assessment of some traditional anti-inflammatory therapies with low APT activity for the management of both acute pain (non-addictive cannabinoids, celery seed, etc.) and chronic inflammation, e.g., Lyprinol (a mussel lipid extract).
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PMID:Prostanoids as friends, not foes: further evidence from the interference by cycloxygenase-inhibitory drugs when inducing tolerance to experimental arthritigens in rats. 1625 16

In our previous work, we demonstrated that Trigonella foenum (TFG) leaves extract can exert analgesic effects in both formalin (F.T.) and tail flick (T.F.) tests. Spinal serotonergic system, but not endogenous opioid system, was involved in TFG induced analgesia (in the second phase of formalin test). Some reports concern the similarity between NSAIDs and TFG extract in many pharmacological effects or the interaction between NSAIDs and purinergic system; so the present study was designed to investigate the relationship between TFG extract and purinergic system or the inhibition of cyclo-oxygenase (COX). We examined the effect of TFG extract on: (1) the response of rabbit platelets to ADP induced aggregation, (2) the contraction of mouse vas deferens induced by alpha,beta-Me-ATP (a P(2) receptor agonist; this receptor mediates the rapid phase of ADP- and ATP-evoked influx of Ca(2+) through a non-specific cation channel in platelets), (3) alpha,beta-Me-ATP induced hyperalgesia in tail flick test in male rats and (4) the specific inhibition of COX-1 and COX-2. Our results showed that TFG extract (0.5, 1, 1.5, 3 mg/ml) inhibited ADP (10(-5) mol) induced platelet aggregation (IC(50)=1.28 mg/ml). alpha,beta-Me-ATP (30 microM) induced isometric contraction in vas deferens while suramin (a P(2) receptor antagonist, 50, 150, 300 microM) or TFG extract (0.5, 1, 2, 3 mg/ml) inhibited this effect significantly (IC(50) were 91.07 microM and 1.57 mg/ml, respectively). Moreover, alpha,beta-Me-ATP (3 microg/rat, i.t.) induced hyperalgesia in tail flick test, but it was prevented by co-injection of alpha,beta-Me-ATP with suramin (120 microg/rat, i.t.) or TFG extract (1mg/rat, i.t.). Effective concentrations of TFG extract in the above mentioned experiments did not inhibit COX enzymes in EIA tests. In conclusion, these results indicate that the blocking of spinal purinoceptors may contribute in the analgesic effect of TFG leaves extract.
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PMID:Probable role of spinal purinoceptors in the analgesic effect of Trigonella foenum (TFG) leaves extract. 1629 92


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