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

Pharmacological properties of LFP83, a non-steroidal analgesic and antipyretic drug, were studied in mice, rats and rabbits. LFP83 is a prodrug of flurbiprofen (FP) which is its active major metabolite in vivo. In experimental models of acetic acid writhing, the Randall and Selitto method, arthritic pain, yeast fever, LPS fever, carrageenin edema and adjuvant arthritis, LFP83 (i.v.) showed remarkable analgesic, antipyretic and antiinflammatory activities; and it was more potent than ketoprofen (i.m.) and aspirin DL-lysine (i.v.). The analgesic activity of LFP83 was equal to or more potent than that of pentazocine, and its duration was longer than those of aspirin DL-lysine and pentazocine. In addition, the analgesic potency of LFP83 was approximately the same or more potent than that of FP (p.o.), and the onset of this analgesic effect began earlier. On the other hand, the ulcerogenic activity of LFP83 on rat gastric mucosa was less than that of FP (p.o.) in both single and consecutive (7 days) administrations. The safety index (UD50/ED50) of LFP83 was three to ten-fold higher than that of FP (p.o.). As mentioned above, LFP83 is a potent analgesic, antipyretic and antiinflammatory drug; and in comparison to oral FP, it has a more potent and immediate effect, weak gastric irritation and high safety index.
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PMID:[Pharmacological studies of a non-steroidal analgesic and antipyretic drug of LFP83]. 278 48

Analgesic and antipyretic effects of proglumetacin maleate (PGM), a new indomethacin (IND) derivative, were investigated in comparison with those of IND on an equimolar-dose basis. The suppression of phenylquinone-induced writhing in mice by PGM was about 0.8 and 2 times as potent as that by IND when given 1 and 4 hr before the phenylquinone injection, respectively. The analgesic activity of PGM in rat silver nitrate arthritis was about 1.5 times more potent than that of IND. PGM was slightly less active in rat adjuvant arthritic pain than IND. On the other hand, PGM provoked a dose-dependent antipyretic effect on the yeast-induced fever in rats within the dose range without affecting the normal body temperature. Furthermore, PGM showed a significant antipyretic effect on LPS-febrile rabbits. Generally, the antipyretic effect of PGM was moderate as compared with that of IND. These analgesic and antipyretic actions of orally administered PGM may be mainly due to its active metabolite, IND. The above results indicate that PGM may be useful for inflammatory diseases associated with pain and/or fever.
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PMID:[Pharmacological studies on proglumetacin maleate, a new non-steroidal anti-inflammatory drug. (2). Analgesic and antipyretic effects]. 349 Apr 20

The value of several serological tests was assessed by studying sera from 30 women with clinical findings of perihepatitis and a high chlamydial antibody titre in the indirect immunofluorescence antibody test (IFAT). The other tests included the complement fixation test and enzyme immunoassays in which the antigen comprised either partially purified particles (EIA kit) or purified major outer membrane protein (MOMP EIA) of Chlamydia trachomatis L2 or lipopolysaccharide isolated from an Re mutant of Salmonella (Re LPS EIA). High IgG titres were noted in most (88-96%) of the patients by MOMP EIA and EIA kit, and in fewer patients (50%) by Re LPS EIA or complement fixation test. Seroconversion was found in 11-44% of the patients for IgG and in 28-36% for IgM; high IgG titre was thus the best diagnostic indicator for each test. The enzyme immunoassay tests have the advantage of being automated either with partially purified corpuscular or purified MOMP antigen and would allow a sensitive easy screening for chlamydial aetiology of women with pain of the right upper quadrant.
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PMID:Comparative sensitivity of different serological tests for detecting chlamydial antibodies in perihepatitis. 389 92

Recent studies have suggested that glia might play a more active role in synaptic function than previously thought. Therefore, the present studies have evaluated the potential role of spinal cord glia in acute nociceptive processing and in the thermal and mechanical hyperalgesia produced by peripheral injury. In the present experiments, we found that: (1) selective inhibition of glia metabolism with intrathecal (i.t.) administration of fluorocitrate (1 nmol) results in a marked, but reversible, attenuation of the persistent thermal and mechanical hyperalgesia produced by intraplantar zymosan (5 mg); (2) selective inhibition of the inducible form of nitric oxide synthase (iNOS) with i.t. aminoguanidine (1 pmol-1 nmol) resulted in a dose-dependent inhibition of the persistent thermal, but not mechanical hyperalgesia produced by intraplantar zymosan (5 mg); (3) i.t. coadministration of interleukin 1 beta (IL1 beta; 10 ng) and interferon gamma (IFN; 1000 U) resulted in expression of the message for iNOS 8 hr after administration assessed using reverse-transcription polymerase chain reaction (RT-PCR) and Southern blot analysis; and (4) i.t. administration of lipopolysaccharide (LPS; 150 micrograms) produced a time-dependent thermal hyperalgesia compared with saline treated-rats (15 microliters). There was no change in mechanical withdrawal thresholds over time following any treatment, except fluorocitrate. We have previously shown that NO plays a significant role in mechanisms of hyperalgesia. In the present experiments we have extended these observations and have now shown a role for iNOS, expressed by glia, in mechanisms of hyperalgesia. These results suggest an unexplored avenue for the development of potential new and novel therapies for pain control.
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PMID:The possible role of glia in nociceptive processing and hyperalgesia in the spinal cord of the rat. 753 31

The spinal cord dorsal horn contains neural mechanisms which can greatly facilitate pain. We have recently shown that 'illness'-inducing agents, such as intraperitoneally administered lipopolysaccharide (LPS; bacterial endotoxin), can produce prolonged hyperalgesia. This hyperalgesic state is mediated at the level of the spinal cord via activation of the NMDA-nitric oxide cascade. However, prolonged neuronal depolarization is required before such a cascade can occur. The present series of experiments were aimed at identifying spinal neurotransmitters which might be responsible for creating such a depolarized state. These studies show that LPS hyperalgesia is mediated at the level of the spinal cord by substance P, cholecystokinin and excitatory amino acids acting at non-NMDA sites. No apparent role for serotonin or kappa opiate receptors was found.
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PMID:Illness-induced hyperalgesia is mediated by spinal neuropeptides and excitatory amino acids. 753

Amine-carboxyboranes are potent anti-inflammatory agents reducing induced edema and pleural effusion at 8 mg/Kg, i.p. They protect against LPS (Salmonella) induced septic shock from 2-8 mg/Kg/day and are effective in blocking pain mediated both locally and centrally. The mode of action of these agents is by blocking release of cytokines from macrophages, thus reducing lysosomal hydrolytic and proteolytic enzyme activities of affected cells. The agents also reduce prostaglandin and leukotriene synthesis by blocking the activities of regulatory enzymes of the respective pathways.
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PMID:Anti-inflammatory activity of amine-carboxyboranes in rodents. 769 71

1. NS-398 (N-[2-cyclohexyloxy-4-nitrophenyl] methanesulfonamide) is a new non-steroidal anti-inflammatory drug (NSAID) with analgesic and antipyretic effects. 2. The anti-inflammatory potency of NS-398 in rat carrageenin-induced edema was as potent as that of indomethacin and 8 times more potent than diclofenac. In rat adjuvant arthritis, NS-398 showed a therapeutic effect comparable to that seen with loxoprofen but less than that seen with indomethacin and diclofenac. 3. The analgesic potency of NS-398 in rat adjuvant arthritic pain was much the same as that of indomethacin, and was about 3-5 times higher than that of diclofenac and loxoprofen. In the Randall-Selitto method in rats, NS-398 was 2-7 times as potent as loxoprofen, diclofenac and indomethacin. In acetic acid-induced writhing in mice, NS-398 was equipotent to indomethacin and diclofenac. 4. In LPS-induced fever in rats, NS-398 was 1.5-4.5 times as potent as loxoprofen and indomethacin, but less potent than diclofenac. 5. NS-398 produced little gastric ulceration in doses of up to 1000 mg/kg, while reference drugs produced distinct stomach lesions in doses of 10-30 mg/kg. 6. NS-398 inhibited prostaglandin (PG) endoperoxide synthase from sheep seminal vesicle microsomes less potent than that of ibuprofen.
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PMID:NS-398, a novel non-steroidal anti-inflammatory drug with potent analgesic and antipyretic effects, which causes minimal stomach lesions. 848 83

Neurodegenerative diseases affecting the midbrain dopaminergic system have been reported to produce spontaneous pains like in Parkinson's disease. Using various pain tests for acute (hot plate test, HPT, tail flick, TFT, paw pressure test, PPT and paw immersion test, PIT) and chronic deafferentation (autotomy, AT, following peripheral neurectomy) pains in rats, we have investigated the effects on these tests of selective chemical lesions with 6-hydroxydopamine (6-OHDA) or/and kainic acid (KA) either in the striatum or in the substantia nigra (SN) and ventral tegmental area (VTA). 6-OHDA lesions of dopaminergic terminals in the striatum decreased significantly the latencies of all nociceptive reflexes (HPT from 11.7 +/- 1.45 s to 7 +/- 1.35 s, TFT from 4.5 +/- 0.15 s to 3.2 +/- 0.16 s and PPT on the contralateral leg from 2.07 +/- 0.45 s to 1.05 +/- 0.085 s) and accelerated the time of onset (from 10.82 +/- 2.3 days to 3.1 +/- 0.52 days) and end (from 29.5 +/- 5.6 days to 5.2 +/- 1.1 days) of AT. These effects were not modified by simultaneous injection of KA and 6-OHDA in the striatum. 6-OHDA lesions in the SN-VTA produced comparable effects to those of similar injections in the striatum, while KA lesions in the SN-VTA did not produce significant changes in the latencies of nociceptive reflexes or in the AT criteria. These results suggest that the dopaminergic system plays a major role in the processing of nociceptive information in the striatum and the limbic areas.
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PMID:Augmentation of nociceptive reflexes and chronic deafferentation pain by chemical lesions of either dopaminergic terminals or midbrain dopaminergic neurons. 909 62

A single injection of Escherichia coli lipopolysaccharide (LPS; i.v. and i.p.) reliably induced peripheral nerve disturbances in male Australian albino Wistar (AaW) rats. Signs developed 6 to 24 h after LPS inoculation and persisted only transiently. Most AaW rats had variable degrees of bilateral hind limb impairment, and rarely had forelimb, tail, or central impairment. Signs included gait abnormalities, proprioceptive loss, and to a lesser extent hind limb weakness and sensory deficits. Signs were more severe in male than female AaW rats and were induced in a number of genetically related rat strains (e.g., AaW and outbred Wistar and inbred Lewis rats, but not Sprague Dawley or inbred Fischer 344 rats). Development and severity of these signs were found not be related to animal body weight, but were dependent on LPS dose. Signs were not associated with LPS-induced alterations in pain perception, or occurrence of spontaneous pain, as indexed by tail-flick and hot-plate tests. Taken together, these data indicate that LPS induced transient peripheral nerve disturbances in rats, the severity of which was influenced by genetic, sex-related, and dose-related factors.
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PMID:Bacterial lipopolysaccharides induce peripheral nerve disturbances in rats that mimic human immune-mediated polyneuropathies. 930 8

Several cytokines and LPS regulate the population of the B1 receptors (B1Rs) for kinins; these are responsive to des-Arg9-bradykinin (BK) and Lys-des-Arg9-BK. B1R activation contributes to inflammatory vascular changes and pain. Aortic rings isolated from normal rabbits and incubated in vitro in Krebs physiological medium were used as a model of tissue injury. From a null level of response, these rings exhibit a time- and protein synthesis-dependent increase in the maximal contractile response to des-Arg9-BK. Exposure to exogenous IL-1beta or epidermal growth factor (EGF) considerably increases the process of sensitization to the kinins. Freshly isolated control aortic rings showed high mitogen-activated protein (MAP) kinase activities (persistent activation of p38, but less prolonged for extracellular signal-regulated kinase and c-Jun-N-terminal kinase/stress-activated protein kinase pathways) relatively to the basal activities found in various types of cultured cells. IL-1beta or EGF further increased the activities of the extracellular signal-regulated kinase and c-Jun-N-terminal kinase/stress-activated protein kinase MAP kinases. The inhibitor of the p38 MAP kinase, SB 203580 (10 microM), massively (approximately 75%) and selectively inhibited the spontaneous sensitization to des-Arg9-BK over 6 h. SB 203580 also significantly reduced the development of the response to des-Arg9-BK as stimulated by IL-1 or EGF. Both spontaneous and IL-1beta-stimulated up-regulation of responsiveness to des-Arg9-BK were significantly inhibited by the MAP kinase extracellular signal-regulated kinase kinase 1 inhibitor PD 98059 (approximately 40%). The protein kinase inhibitors failed to inhibit protein synthesis and to acutely inhibit the contractile effect of des-Arg9-BK, suggesting that they do not influence B1 receptor transduction mechanisms. In cultured aortic smooth muscle cells stimulated with EGF, MAP kinase activation preceded B1R mRNA induction. Protein kinase inhibitors reveal the role of cell injury-controlled MAP kinase pathways, and singularly of the p38 pathway, in the induction of B1R.
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PMID:Role of the mitogen-activated protein kinases in the expression of the kinin B1 receptors induced by tissue injury. 957 May 62


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