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)

Ibuprofen is a derivative of propionic acid that was originally marketed in the United States as an antirheumatic agent in 1974. In 1979, it was approved for use as an analgesic. Of the 18 published double-blind clinical trials reviewed, only 6 were well designed. These six studies provide strong evidence that ibuprofen is effective for dental pain due to tooth extractions, dysmenorrhea and episiotomy pain. Thus, ibuprofen appears to be an effective drug for mild to moderate pain. It is as effective or more effective than aspirin, codeine or propoxyphene. Recommended initial dosage is 300 mg every six hours, increasing as needed to 400 mg every four hours. Adverse effects are relatively minor and infrequent.
 ...
PMID:Evaluation of the analgesic efficacy of ibuprofen. 676 84

A double-blind three-way crossover design in the treatment of dysmenorrhea comparing a propionic acid derivative (ibuprofen) and a fenamate (mefenamic acid) with a placebo showed that both ibuprofen and mefenamic acid are generally superior to placebo. Statistically significant results were obtained in favor of the study drugs over placebo for the pain relief afforded by the treatments (as graded by patients) and the visual analog pain relief score, which not only ranks but also indicates the degree of pain relief as a percentage of total relief (100%). Pairwise comparisons for the ranks found mefenamic acid significantly superior to placebo (P less than .001) and ibuprofen marginally superior to placebo (P less than .06), while the visual analog pain relief scale demonstrated mefenamic acid and ibuprofen superior to placebo (P less than .001 and P less than .01, respectively). For both the patient ranking of pain relief by treatment and the visual analog pain relief scale, the results showed no significant differences between ibuprofen and mefenamic acid. Side effects occurred in 11 ibuprofen cycles, five mefenamic acid cycles, and ten placebo cycles of the 48 cycles with each agent. These were generally of minor severity or importance and were not statistically different. The need for additional analgesics and the ability to pursue normal daily activity were not different for any treatment group. The findings of this study indicate no clinical difference between a propionic acid derivative such as ibuprofen and a fenamate such as mefenamic acid in the treatment of dysmenorrhea.
 ...
PMID:A double-blind comparison of a propionic acid derivative (ibuprofen) and a fenamate (mefenamic acid) in the treatment of dysmenorrhea. 683 17

Anti-inflammatory activity of 2-[p-(2-imidazo[1,2-a]pyridyl) phenyl]propionic acid (Y-9213, miroprofen) was studied on various experimental models. Miroprofen was found to be as active as indomethacin against the exudative inflammation such as pleuritis in rats induced by Evans blue-carrageenin and the peritonitis in mice induced by acetic acid, and against the local Shwartzman reaction in rabbits. Miroprofen also inhibited the formation of edema induced by carrageenin or kaolin in rats' paws at lower doses. Against the proliferation of connective tissues, miroprofen showed the inhibitory action at higher doses. The ulcerogenic activity of miroprofen in rats was less potent than that of indomethacin, and as active as that of phenylbutazone. These findings indicate that miroprofen may be more effective in suppressing pain responses and acute inflammation accompanied with increased vascular permeability.
 ...
PMID:Anti-inflammatory activity of an imidazopyridine derivative (miroprofen). 719 60

Flurbiprofen is a propionic acid-derived non-steroidal anti-inflammatory drug (NSAID) used widely in the treatment of rheumatism and non-arthritic pain. The pharmacokinetics of topically and orally administered flurbiprofen were compared in a two-part, open study involving healthy adult volunteers. In the first (cross-over) part of the study, 12 Caucasians were randomized to receive either a single oral dose of 50 mg flurbiprofen or a single topical application of a novel 40 mg flurbiprofen-containing patch on the right wrist for 12 h. In the second part of the study, each subject applied a flurbiprofen-containing patch twice daily to the same wrist for 7 days. Plasma concentrations of flurbiprofen and urinary concentrations of the NSAID and its metabolites were measured by high-performance liquid chromatography assay, to enable comparison of the pharmacokinetic parameters for delivery of the drug by both routes. Maximum concentrations of the NSAID in plasma (Cmax) were much lower after a single application of the topical 40 mg flurbiprofen patch than after a single oral dose of 50 mg of the NSAID (mean +/- SD: 43 +/- 16 ng/ml versus 5999 +/- 1300 ng/ml, respectively). After repeated application of the topical patch, Cmax increased only slightly to 103 +/- 57 ng/ml. The mean relative bioavailability of flurbiprofen from the patch was 3.5 +/- 1.7%, calculated from plasma area under the curve data and 4.4 +/- 2.8% from urinary excretion data.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Pharmacokinetic comparison of oral and local action transcutaneous flurbiprofen in healthy volunteers. 765 70

Immunohistochemical staining for the glutamate receptor subtypes N-methyl-D-aspartate (NMDA), kainate, and alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) results in a significant number of labeled unmyelinated axons in the glabrous skin of the rat hindpaw. Injection of glutamate into the rat hindpaw results in behavioral changes interpreted as mechanical allodynia and mechanical hyperalgesia. The anatomical findings provide a reasonable explanation for the action of the exogenous peripheral glutamate, namely that activation of these receptors leads to increased primary afferent activity in unmyelinated axons and thus to pain behaviors. AMPA receptors are frequently associated with small clear vesicles in the axoplasm of the unmyelinated axons, many of which have been previously shown to contain high concentrations of glutamate. This finding indicates that these might be autoreceptors and so glutamate itself might regulate certain types of peripheral impulse traffic. The presence of peripheral glutamate receptors associated with unmyelinated axons suggests the possibility that glutamate antagonists applied peripherally might prevent or attenuate some pain-related behaviors.
 ...
PMID:Localization and activation of glutamate receptors in unmyelinated axons of rat glabrous skin. 854 47

Tiaprofenic acid is a nonsteroidal anti-inflammatory drug (NSAID) used in the treatment of patients with rheumatic diseases and other clinical conditions of pain and inflammation. Like other propionic acid derivatives, tiaprofenic acid is effective and generally well tolerated. Comparative studies in patients with rheumatoid arthritis or osteoarthritis receiving tiaprofenic acid 600 mg/day demonstrated improvements in pain intensity, duration of morning stiffness, articular index and other clinical variables which were similar to those achieved with alternative NSAIDs. Tolerability was also comparable between tiaprofenic acid and other NSAIDs in most trials; the most frequently reported adverse events involved the gastrointestinal tract. Some studies showed a trend towards fewer patient withdrawals because of adverse events with tiaprofenic acid than with NSAIDs such as indomethacin. Current evidence suggests that nonbacterial cystitis is more likely to be associated with tiaprofenic acid than with other NSAIDs. This reaction should, however, be considered in the perspective of its infrequent occurrence and its typical reversibility, and against the wider background of the established usage of tiaprofenic acid and its overall tolerability profile which is similar to that of other NSAIDs. Unlike indomethacin, tiaprofenic acid was not associated with increased cartilage degradation in a recently completed large clinical trial known as LINK, which evaluated the effects of long term administration in patients with osteoarthritis of the knee. Thus, tiaprofenic acid is an established option among the range of NSAIDs used in the treatment of patients with rheumatic diseases, with efficacy and tolerability profiles that are relatively well characterised. The availability of a sustained release dosage form of tiaprofenic acid, which has a similar efficacy and tolerability profile to the standard formulation, provides a convenient once daily dosage regimen.
 ...
PMID:Tiaprofenic acid. A reappraisal of its pharmacological properties and use in the management of rheumatic diseases. 861 71

In spinal cord neurons in anesthetized rats, the role on neurokinin A and neurokinin-2 receptors in the processing of nociceptive information from the knee joint was studied. The specific non-peptide antagonist at the neurokinin-2 receptor, SR48968, its inactive R-enantiomer, SR48965, neurokinin A, substance P and (RS)-alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA), were administered ionophoretically close to neurons with input from the knee joint. SR48968 reduced the effects of exogenous neurokinin A, but not those of exogenous substance P and AMPA, indicating selective blockade of neurokinin-2 receptors. In most neurons with input from the normal knee joint, SR48968 reduced dose-dependently the responses to noxious pressure with applied to the knee, and in approximately 50% of the neurons the responses to innocuous pressure. The administration of SR48968 during the induction of an experimental joint inflammation markedly attenuated the development of inflammation-evoked hyperexcitability. In hyperexcitable neurons with input from the inflamed joint, SR48968 reduced the responses to noxious and innocuous pressure. The relative reduction of the responses was more pronounced than in neurons with input from the normal joint. None of the effects of SR48968 was mimicked by SR48965. These data show that neurokinin-2 receptors are involved in the spinal processing of nociceptive information from the normal joint. Furthermore, neurokinin-2 receptors must be coactivated at an early stage of inflammation, to allow the generation of hyperexcitability. Finally, neurokinin-2 receptors are involved in maintenance of hyperexcitability during inflammation. In summary, spinal neurokinin-2 receptors are important in the generation of pain in the normal and inflamed joint.
 ...
PMID:The role of spinal neurokinin-2 receptors in the processing of nociceptive information from the joint and in the generation and maintenance of inflammation-evoked hyperexcitability of dorsal horn neurons in the rat. 871 96

The present study investigated the role of N-methyl-D-aspartate (NMDA) and non-NMDA glutamate receptor subtypes in peripheral pain transmission. Activation of NMDA, alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) and kainate acid (KA) receptors in glabrous skin of the rat hindpaw resulted in mechanical allodynia and mechanical hyperalgesia. These agonist-induced pain behaviors were attenuated following peripheral injection of appropriate antagonists (MK-801 and CNQX). Thus, activation of NMDA, AMPA or KA receptors at the level of the peripheral nerve terminal can produce nociceptive behavior. These data suggest that topical application of glutamate receptor antagonists may be useful in treating pain disorders. Since all three receptor subtypes are involved in peripheral pain transmission, however, it will be necessary to antagonize multiple glutamate receptor subtypes to achieve effective pain relief.
 ...
PMID:Peripheral administration of NMDA, AMPA or KA results in pain behaviors in rats. 872 68

The spinal cord dorsal horn contains neural mechanisms which can greatly facilitate pain. It is well established that excitatory amino acids, aspartate and glutamate, are involved in the spinal transmission of nociceptive information and in the development of hyperalgesia. In the present study, intrathecal (i.t.) administration of alpha-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid (AMPA), a structural analog of L-glutamate, produced a dose-dependent behavioural syndrome characterized by caudally directed biting in mice. We demonstrated that peripheral pre-administration of the AMPA receptor antagonists 2,3-dihydroxy-6-nitro-7-sulfamoylbenzo(F)quinoxaline (NBQX, 10-100 mg/kg s.c.) and 1-(4-aminophenyl)-3-methylcarbamoyl-4-methyl-3,4-dihydro-7, 8-methylene-dioxy-5H-2,3-benzo-diazepine-HCl (GYKI 53655, 3-10 mg/kg s.c.), and also of the NMDA receptor antagonist 5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5, 10-imine maleate (MK 801, 0.3-1 mg/kg s.c.) reversed this effect. These findings suggest that the hyperalgesia induced by the i.t. injection of AMPA in mice involves the activation of both NMDA and non-NMDA excitatory amino acid receptor sites.
 ...
PMID:Pharmacological characterization of AMPA-induced biting behaviour in mice. 881 40

Inhibition of spinal glutamate receptors induces antinociceptive effects in numerous animal models of pain. The present study compares the effects of intrathecally administered N-methyl-D-aspartate (NMDA) and non-NMDA glutamate receptor antagonists on nociceptive responses in the tail flick test. Potency of antagonists at NMDA and alpha-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid (AMPA) receptors was first measured by electrical assays in Xenopus oocytes expressing rat cerebral cortex poly(A)+ RNA. Subsequently, Swiss Webster mice were injected intrathecally with the antagonists and tested for antinociception. The drugs tested were: NBQX and GYKI-52466, selective AMPA receptor antagonists, ketamine, MK-801, R(+) HA-966 and ACEA-0762, selective NMDA receptor antagonists, and ACEA-1031, ACEA-1328 and ACEA-0593, NMDA receptor antagonists that also show inhibition of non-NMDA receptors. Selective NMDA receptor antagonists induced essentially no antinociceptive effects in the tail flick test. Antinociceptive activity generally correlated with inhibition of AMPA receptors. The exception was the non-competitive AMPA receptor antagonist GYKI-52466, which was unexpectedly weak. This may be due to inadequate dosing, because the compound has limited solubility, or may be due to differences in the non-NMDA receptor subtype-selectivity profile of GYKI-52466 as compared to competitive antagonists such as NBQX. Overall, our results suggest that inhibition of spinal non-NMDA receptors is the primary, and necessary, mechanism of antinociception by these drugs in the tail flick test in mice.
Pain 1997 Mar
PMID:Antinociceptive effects of NMDA and non-NMDA receptor antagonists in the tail flick test in mice. 910 7


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