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Query: UMLS:C0030193 (pain)
 261,466 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Ketorolac tromethamine is a highly potent member of a class of compounds having both analgesic and antiinflammatory activity. In animal pain models using underlying inflammation, ketorolac markedly inhibited the pain response and increased the pain threshold; it did not exhibit any narcotic or central nervous system depressant effects. It was also active in rat models of acute and chronic inflammation and pyresis. These activities are mediated primarily by potent prostaglandin cyclooxygenase inhibitory activity. Mild central nervous system and cardiovascular effects occurred only at doses far greater than those required for analgesic and antiinflammatory activity. Solutions of ketorolac tromethamine are not irritating. When given intramuscularly to rabbits (0.31-5% solutions), no drug-related irritation or changes in serum creatine phosphokinase were seen. The agent was not irritating when applied to the skin or eyes (less than or equal to 0.5% solutions) of animals.
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PMID:The pharmacologic activity of ketorolac tromethamine. 208 10

Pharmacological activities of mofezolac were investigated in experimental animal models and compared with those of indomethacin, ibuprofen, mefenamic acid, aspirin and aminopyrine. Mofezolac showed a potent suppression of various writhing models in mice or rats; and its potency was slightly lower than that of indomethacin, but was higher than those of the other reference drugs. Thus, mofezolac was especially active against chemically induced writhing and also in the phenylquinone induced intraperitoneal dye leakage reaction in mice. Mofezolac also has a potent inhibitory activity on the algesic responses induced by the mechanical stimulus of the inflammed tissue. Mofezolac exhibited a therapeutic effect comparable to indomethacin in the urate synovitis in dogs. Considering the anti-inflammatory and antipyretic actions, mofezolac was obviously less effective than indomethacin, and its potency was similar to that of ibuprofen. The ulcerogenic effect of mofezolac on the gastric mucosa was far weaker than that of indomethacin. In in vitro studies, the prostaglandin biosynthesis and platelet aggregation were inhibited to the same extent by both mofezolac and indomethacin. Accordingly, it may be considered that the actions of mofezolac are due to the inhibition of cyclooxygenase. Our result suggest that mofezolac can be a useful drug that shows a rapid pain-relieving activity in acute inflammations.
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PMID:[Pharmacological profile of mofezolac, a new non-steroidal analgesic anti-inflammatory drug]. 210 26

Subplantar injection of 250 micrograms of trypsin in the rat resulted in a biphasic increase in pain sensitivity (hyperalgesia) with peaks at 10 and 150 min separated by a period of decreased sensitivity to pain (hypoalgesia). Hyperalgesia was assessed by a decrease in response latency to a 3.0-kg force applied to the injected hind limb. Response latencies at 150 min were increased in a dose-dependent manner by pretreatment at 90 min with acetaminophen; phenacetin; the arachidonate cyclooxygenase inhibitors aspirin, indomethacin, and ibuprofen; and the opiate analgesics codeine and morphine. ED50s of 17, 13, 10, 0.48, 1.6, 3.9 and 1.2 mg/kg p.o. were obtained for these drugs, respectively. The hyperalgesia present at 150 min was not affected by pretreatment with antiinflammatory steroids, an antihistaminic, an antiserotonin agent, and an anticholinergic. We recommend measurement of drug-induced increase in response latencies produced 150 min after injection of 250 micrograms of trypsin as the basis for a new sensitive and selective analgesic assay. ED50s obtained in this assay correlate well with doses that are used clinically to produce analgesia. Development of the hypoalgesic component was selectively inhibited by pretreatment with an antiserotonin agent. Additional drug studies indicated that the algesic response to the subplantar injection of trypsin is the resultant of independent, temporally overlapping hyperalgesic and hypoalgesic components.
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PMID:New analgesic assay utilizing trypsin-induced hyperalgesia in the hind limb of the rat. 230 51

Oxygenation of arachidonic acid is increased in inflamed tissues. In this condition products of two enzymic pathways--the cyclooxygenase and the 5-lipoxygenase producing respectively prostaglandins and leukotrienes--are elevated. Of the cyclooxygenase products, PGE2 and of the lipoxygenase products, LTB4 are the strongest candidates for mediating inflammation. Non-steroidal anti-inflammatory drugs which inhibit the cyclooxygenase, and corticosteroids are used to treat such disorders. Both types of drugs produce adverse side-effects on prolonged use. Ginger is reported in Ayurvedic and Tibb systems of medicine to be useful in rheumatic disorders. Seven patients suffering from such disorders reported relief in pain and associated symptoms on ginger administration.
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PMID:Ginger (Zingiber officinale) and rheumatic disorders. 250 34

Arachidonic acid metabolites, prostaglandins (PGs), thromboxanes (TXs), and leukotrienes (LTs), are classified as a type of autacoids. They are not stored in the cells, but stored as a precursor acid, arachidonic acid, in membrane phospholipids. Various physiological stimuli activate phospholipase A2 and release arachidonic acid, which is converted to 1 or 2 products by related enzymes within a few minutes, depending upon individual cell functions. The metabolites are readily inactivated in aqueous solution and in the body. The structures of the various metabolites are quite similar, but their pharmacological actions vary from metabolite to metabolite and some exert opposite actions to those of others. The metabolites play some pivotal roles in physiological or pathophysiological responses such as pain sensation, fever, plasma leakage and skin erythema. Thus, non-steroidal anti-inflammatory drugs, like aspirin, exert their actions through cyclooxygenase inhibition at low doses. PGE2 can be detected in the exudate of acute inflammatory models, and the simultaneous release of PGE2 with bradykinin induces a large increase in plasma leakage and triggers exudate accumulation. LTB4 induces extravasation of PMN leukocytes at the microcirculatory level and is generated in the reperfused area of infarcted cardiac tissue after ligation of rat coronary artery, but in the latter case, the leukocyte migration was not solely induced by LTB4, which was replaced by a complement component (C5a). LTC4 may be involved in ethanol injury of the gastric mucosa and endogenous PGE2 prevents this injury. The real roles of individual arachidonic acid metabolites have been gradually disclosed, but most of the roles are still yet to be clarified.
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PMID:[Pharmacology of prostaglandins; their profile and characterization in the body]. 250 10

Oxphaman and particularly oxphalin, among other phenolic azomethines, have been proven as strong inhibitors of lipoxygenases (LOX) from reticulocytes, soybean, thrombocytes as well as of quasi-LOX (hemoglobin) with IC50 values which correspond with those of known LOX inhibitors. The 5-LOX is likewise strongly, the cyclooxygenase of sheep seminal vesicles only weakly inhibited. Nevertheless, antiinflammatory effectivity was found in some carrageenin-induced inflammatory models of the rat as well as in the arachidonic acid- and croton oil-induced ear oedema of the mouse. Adjuvant arthritis, experimental pain, skin permeability and allergy models (anaphylactic paw oedema, cutaneous anaphylaxis, asthma, picryl chloride ear oedema) were not, only weakly or irregularly influenced. In the guinea pig ileum a certain antihistaminic, anticholinergic and leukotriene antagonistic activity was found. An inflammation-induced vasodepression (anaphylactic shock, dextran paw oedema. UV irradiation) was dose-dependently prevented or even reversed, obviously on the basis of oxygen radical scavenging.
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PMID:[The pharmacology of the lipoxygenase inhibitors oxphaman (1-(2,5-dihydroxybenzylidene)aminoadamantane) and oxphalin (1-(3,4-dihydroxybenzylidene)-2,4,6-trimethylaniline]. 251 86

The physiological basis of the pain and hyperalgesia observed in patients with Raynaud's phenomenon (RP) is unknown. Since estrogen-induced effects on sympathetic postganglionic neurons (SPGNs) have been implicated in the vasomotor abnormalities in patients with RP, we have studied the effects of estradiol on nociceptive thresholds and noradrenaline sensitivity in a nociceptive flexion reflex in the rat. We report that estradiol induces a catecholamine sensitive hyperalgesia. This hyperalgesia is antagonized by yohimbine (an alpha 2-adrenergic antagonist) but not prazosin (an alpha 1-adrenergic antagonist) as well as by inhibitors of the cyclooxygenase pathway of arachidonic acid metabolism. These data are compatible with the hypothesis that the sensory abnormalities observed in patients with RP may depend on estradiol-induced changes in SPGN, resulting in a sympathetically-dependent production of cyclooxygenase products of arachidonic acid.
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PMID:Beta-estradiol induced catecholamine-sensitive hyperalgesia: a contribution to pain in Raynaud's phenomenon. 254 46

Manoalide, a non-steroidal sesterterpenoid isolated from a marine sponge, is a potent analgesic and antiinflammatory compound. Manoalide inhibits phospholipase A2 from extracellular sources (snake venoms, bee, etc.), the release of arachidonic acid from rabbit polymorphonuclear leukocytes as well as calcium mobilization. This suggests that the anti-inflamatory effect might be caused by the regulation of eicosanoid biosynthesis. The macrophage plays a major role in the immune response and the inflammatory process, it has the capacity to synthesize and secrete arachidonic acid oxygenation products derived from both cyclooxygenase and lipoxygenase catalyzed pathways, and has been used extensively to study the effect of inhibitors of phospholipases, cyclooxygenase and lipoxygenase enzymes. Our results demonstrate that Manoalide modified the release of arachidonic acid and its further metabolism into prostaglandins and leukotrienes in mouse cultured peritoneal macrophages stimulated by phorbol myristate acetate, calcium ionophore A23187 and zymosan. Since eicosanoids have been shown to cause pain, we studied the possibility that the analgesic effect of Manoalide might be correlated with a decrease of eicosanoid release in vivo. The fact that Manoalide reduced both zymosan-induced peritoneal writhing in the mouse and the synthesis of both 6-keto-prostaglandin F1 alfa and leukotriene C4 suggests that the analgesic effect of Manoalide is at least in part linked to the inhibition of eicosanoid production in vivo. Since it has been shown that eicosanoids have immunoregulatory functions, a future possibility is that a phospholipase A2 inhibitor such as Manoalide may prove useful to investigate the biological role of eicosanoid metabolites on the immune function.
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PMID:[Manoalide: a new phospholipase A2 inhibitor of marine origin with potential immunoregulatory effect]. 264 Apr 87

Subplantar injection of 0.10 micrograms of serotonin in the rat resulted in a brief period (0-20 min) of increased pain sensitivity to an applied force (hyperalgesia) which preceded a longer period (40-120 min) of decreased pain sensitivity (hypoalgesia). The magnitude of each of these changes and the duration of the hypoalgesia were dose-dependent. The development of hyperalgesia was selectively and dose dependently reduced by inhibitors of arachidonate cyclooxygenase. The hypoalgesia was selectively and dose dependently reduced by the serotonin antagonist methysergide. Selective inhibition of the hyperalgesia by aspirin and of the hypoalgesia by methysergide revealed that components of both hyperalgesia and hypoalgesia were present in the 10-120 min interval. These findings, the level of serotonin reported to be released in rat dermal tissue, and selective drug inhibition studies suggest that some irritant-induced changes in algesia measured in the rat hindlimb result from release of dermal stores of serotonin. Selective inhibition of the hypoalgesic component of the hindlimb irritant trypsin by the antiserotonin agent methysergide supports this hypothesis. The principal conclusion derived from these studies is that the algesic response to the subplantar injection of a single agent can be the resultant of independent, temporally overlapping hyperalgesic and hypoalgesic components each of different intensity and pharmacological sensitivity.
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PMID:Pharmacological characterization of the algesic response to the subplantar injection of serotonin in the rat. 276 20

In order to determine the role of peripheral prostanoids in a newly developed mechanical visceral pain model, several NSAIDs were studied. Systemic acetylsalicylic acid and mefenamic acid, in doses known to produce cyclooxygenase inhibition, produced limited or no analgesia using a duodenal distension model and a behavioral scale for assessment. In contrast, indomethacin at 1 mg/kg, a dose 1/100th of the highest dose of the above compounds, had a marked analgesic effect in the visceral pain model (32% of control response). These data suggest that a duodenal distension stimulus does not have a peripheral prostaglandin E2-mediated nociceptive mechanism. Furthermore, the results obtained with indomethacin support an alternate, possibly central nonprostanoid visceral antinociceptive action.
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PMID:The differentiation of NSAIDs and prostaglandin action using a mechanical visceral pain model in the rat. 278 Jul 82


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