Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0030193 (pain)
 261,466 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Inhibition of cyclooxygenase by nonsteroidal anti-inflammatory drugs (NSAIDs) in the periphery is commonly accepted as the primary mechanism by which these agents produce a selective attenuation of pain (analgesia). NSAIDs are now shown to exert a direct spinal action by blocking the excessive sensitivity to pain (hyperalgesia) induced by the activation of spinal glutamate and substance P receptors. These findings demonstrate that the analgesic effects of NSAIDs can be dissociated from their anti-inflammatory actions. Spinal prostanoids are thus critical for the augmented processing of pain information at the spinal level.
 ...
PMID:Hyperalgesia mediated by spinal glutamate or substance P receptor blocked by spinal cyclooxygenase inhibition. 138 21

One of the features of inflammation is increased oxygenation of arachidonic acid which is metabolized by two enzymic pathways--the cyclooxygenase (CO) and the 5-lipoxygenase (5-LO)--leading to the production of prostaglandins and leukotrienes respectively. Amongst the CO products, PGE2 and amongst the 5-LO products, LTB4 are considered important mediators of inflammation. More than 200 potential drugs ranging from non-steroidal anti-inflammatory drugs, corticosteroids, gold salts, disease modifying anti-rheumatic drugs, methotrexate, cyclosporine are being tested. None of the drugs has been found safe; all are known to produce from mild to serious side-effects. Ginger is described in Ayurvedic and Tibb systems of medicine to be useful in inflammation and rheumatism. In all 56 patients (28 with rheumatoid arthritis, 18 with osteoarthritis and 10 with muscular discomfort) used powdered ginger against their afflictions. Amongst the arthritis patients more than three-quarters experienced, to varying degrees, relief in pain and swelling. All the patients with muscular discomfort experienced relief in pain. None of the patients reported adverse effects during the period of ginger consumption which ranged from 3 months to 2.5 years. It is suggested that at least one of the mechanisms by which ginger shows its ameliorative effects could be related to inhibition of prostaglandin and leukotriene biosynthesis, i.e. it works as a dual inhibitor of eicosanoid biosynthesis.
 ...
PMID:Ginger (Zingiber officinale) in rheumatism and musculoskeletal disorders. 149 22

A new behavioral test is described in which quantitation is independent of the observer and is sensitive to all classes of analgesics. A computer-assisted device measures the period during which a rat hind paw fails to touch the surface of a rotating cylinder for 1 min (paw elevation time). Intra-articular injection of carrageenin induces a progressive and dose-dependent incapacitation of the limb. The maximum paw elevation time is attained 3-4 h after carrageenin challenge. The model showed dose-dependent sensitivity to (a) a central acting opiate (morphine, ID50 = 1.5 mg/kg, i.p.), (b) cyclooxygenase inhibitors (indomethacin, ID50 = 0.8 mg/kg, i.p.; diclofenac, ID50 = 0.22 mg/kg, i.p.), and (c) peripheral analgesics which directly antagonize nociceptor hypersensitivity: dipyrone (ID50 = 21 mg/kg, i.p.), N-methyl-nalorphine (ID50 = 14 mg/kg, i.p.) and BW443C (ID50 = 17.5 mg/kg, i.p.). The knee-joint carrageenin incapacitation was also blocked by the sympatholytics, propranolol and guanethidine. After the blockade by either indomethacin or guanethidine, intra-articular injections of prostaglandin E2 or dopamine, respective, reversed carrageenin-induced incapacitation. These results suggest that during inflammatory articular incapacitation cyclooxygenase and sympathomimetic mediators are involved, as has been suggested for the rat paw carrageenin hyperalgesia test and formalin test.
Pain 1992 Mar
PMID:Rat knee-joint carrageenin incapacitation test: an objective screen for central and peripheral analgesics. 159 66

The derivatives of arachidonic acid are generally called by the term eicosanoid. Arachidonic acid is a starting material for a series of biologically highly active metabolites that are formed either through cyclooxygenase, e.g., the prostaglandins (PG), or through various lipoxygenase ways, e.g., hydroxyarachidonic acids (HETE), leukotriene (LT), and peptide-LT. Eicosanoids also take part in menstrual bleeding; in dysmenorrhea also cyclooxygenase inhibitors, e.g., indomethacin have been proven to fight pain in addition to spasmolytics and the preventive action of hormonal contraceptives. PGs and peptide-LT could be shown in relative high concentrations in the endometrium of dysmenorrheic women. An analytic method in which menstrual blood was used as test material was developed. Women were given standardized tampons and holders filled with acidified alcohol. The holders were weighed for determination of the amount of blood. A special high performance liquid chromatography separation system was developed for purification, and radioimmunoassay was subsequently used for analysis of 60keto-PGF1alpha, and PGE2. 103 tampons of 14 subjects from 24 menstrual cycles were evaluated in 4 groups; no hormonal contraceptive use, contraceptive use, no pain, and pain. The taking of a pill significantly affected the blood volume; it was only 1/2 as much as in the control group without the taking of a pill. In the control group with a pill and pain 12 HETE was quantitatively the most important eicosanoid with a 60% share. F2alpha dominated among PGs. In patients with pain without pill use the average values of 6-keto, PGE2, 12-HETE, and LTB 4 were 50% higher. After pill use PG concentrations dropped significantly by 80% compared with controls. 12-HETE and PGF2alpha were the main metabolites of arachidonic acid in menstrual blood, in pain some metabolites were higher, and OCs reduced eicosanoid excretion significantly.
 ...
PMID:[Effect of hormonal contraceptives on eicosanoid content of menstrual blood]. 179 Sep 85

Acetylsalicylic acid (ASA) is a short-acting oral inhibitor of the cyclooxygenase enzyme. Ingestion of ASA is associated with a decrease in prostaglandins, including those of the E2 series, as well as prostacyclin, and thromboxane. Consumption of therapeutic doses is associated with decreased pain and inflammation and is therefore used in a variety of inflammatory conditions. Platelet aggregation is also inhibited. Because of these observations, and the fact that platelet aggregation has been noted to be altered during exercise, the effects of ASA on exercise tolerance was of interest. We studied 17 healthy male volunteers who regularly ran as a source of exercise. During the study they ingested either 650 mg of ASA or placebo 30 min before running 2 miles (3.2 km). Outcome of the double-blind crossover study was measured by the time required to run a 2-mile distance. No differences between ASA or placebo were noted in the subjects. These data suggest that 650 mg of ASA as a premedication has little effect on exercise performance in normal endurance runners. However, whether ASA may affect pain after exercise or whether other dosage intervals would be more beneficial needs further study.
 ...
PMID:A double-blind, placebo-controlled study of acetylsalicylic acid (ASA) in trained runners. 180 34

Meclofenamic acid is a nonsteroidal anti-inflammatory drug (NSAID) approved for use in arthritis (osteo and rheumatoid), analgesia (mild to moderate pain), dysmenorrhea, and heavy menstrual blood loss (menorrhagia). At least three different biochemical effects have been defined for meclofenamic acid. It is a potent inhibitor of the enzyme cyclooxygenase, thereby inhibiting the production of prostaglandins. It also inhibits the release of 5-HETE and LTB4 from human neutrophils stimulated with calcium ionophore and antagonizes the response of tissues to certain prostaglandins. These mechanisms may explain in part the pharmacological profile and clinical effectiveness of this compound. The rapid onset of activity of meclofenamic acid and its duration of action may be the result of its pharmacokinetic profile. Sodium meclofenamate is completely bioavailable from capsules relative to an oral suspension dosage form. Maximum meclofenamic acid plasma concentrations are achieved in 0.5-2 h following doses of capsules. Meclofenamic acid is extensively metabolized. One of the metabolites, metabolite 1, is approximately 20% as active as the parent compound in inhibiting cyclooxygenase activity in vitro. This metabolite accumulates in plasma during repeated dosing. It is possible that this metabolite may contribute to at least some of the activity observed following administration of sodium meclofenamate.
Clin J Pain 1991
PMID:Pharmacology, pharmacokinetics, and therapeutic use of meclofenamate sodium. 181 May 20

The modern therapy of the pain of inflammatory rheumatic disease and osteoarthritis is based on several advances in molecular biology, which are reviewed in this paper. Inhibition of the ubiquitous enzyme cyclooxygenase by the nonsteroidal anti-inflammatory drugs including the salicylates prevents the production of endoperoxides, which are pro-inflammatory, and prostaglandins E2 and I2, which sensitize peripheral pain receptors. In addition, a fundamental understanding of neural tracts that inhibit the pain signal has introduced the concept of giving low dose tricyclic antidepressants for chronic pain to block the re-uptake of serotonin from the neural cleft of synapses. This amplifies the effect of serotonin and catecholamines, which are neurotransmitters for these inhibitory tracts.
 ...
PMID:The pharmacological control of musculoskeletal pain. 186 25

Indomethacin suppository and aspirin inhalation reduced the amounts of sputum in the patients with bronchiectasis and chronic bronchitis. A 67-year-old woman with bronchiectasis received indomethacin suppository to relieve the lumbar pain. After the start of indomethacin, a reduction in the amount of sputum was observed and the volume of sputum returned to pretreatment levels after the cessation of indomethacin. Levels of cyclooxygenase products in the sputum during indomethacin was also much lower than their levels after discontinuance of indomethacin. A 64-year-old man with chronic bronchitis was also administered inhaled aspirin to control the sputum volume. Both indomethacin suppository and aspirin inhalation reduced the amounts of sputum. In addition to these cases, a 31-year-old woman with bronchial asthma was tried to control the sputum production with indomethacin, but it had no effect on the sputum volume. It is suggested that these drugs may be useful in the treatment of excessive sputum in bronchiectasis and chronic bronchitis.
 ...
PMID:Effect of cyclooxygenase inhibitor on excessive sputum. 190 74

Pain induced by a stimulus that is normally not painful is referred to as hyperalgesic pain. Inhibition of arachidonic acid metabolism and/or sympathectomy have been found to be effective treatment for this type of pain. We propose that the lowered pain threshold is induced by arachidonic acid metabolites produced in inflamed tissue or by sympathetic postganglionic neurons after nerve injury. The most extensively studied hyperalgesic mediators are prostaglandin E(2) (PGE(2)) and prostacyclin (PGI(2)), products of the cyclooxygenase pathway of arachidonic acid metabolism, whose production is inhibited by nonsteroidal antiinflammatory analgesics (NSAIAs). Recent studies, however, have demonstrated that products of the NSAIA-resistant lipoxygenase pathway of arachidonic acid metabolism are also hyperalgesic. Their production is inhibited by corticosteroids and current experimental agents.
 ...
PMID:Hyperalgesic pain: a review. 196 69

E5090 is a novel orally active inhibitor of IL-1 generation without cyclooxygenase-inhibiting activity. The effects of E5090 on several inflammatory animal models were investigated in rats. In adjuvant arthritis, E5090 suppressed both the paw swelling and the enhancements of ESR and number of peripheral blood leucocytes, like the steroidal antiinflammatory drug prednisolone. However, the thymus was not withered by E5090 though it was by prednisolone. In type II collagen-induced arthritis, E5090 inhibited paw swelling and joint destruction. E5090 was effective in acute inflammatory models such as carrageenin-induced paw edema, and adjuvant-induced local hyperthermia, and also showed analgesic effects against inflammatory pain and antipyretic effects. The results suggest that this orally active inhibitor of IL-1 generation, E5090, may be a therapeutically useful antiinflammatory drug with a novel mechanism of action.
 ...
PMID:Antiinflammatory properties of E5090, a novel orally active inhibitor of IL-1 generation. 206 90


1 2 3 4 5 6 7 8 9 10 Next >>