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

The present study was designed to examine some of the pharmacological properties of venom from the stonefish (Synanceja trachynis), with particular reference to the presence in the venom of pain-producing/enhancing substances. Stonefish venom (1-6 micrograms/ml) produced concentration-dependent contractile responses in guinea-pig isolated ileum. No tachyphylaxis, or reduction in responses with time, was observed to venom (3 micrograms/ml) in ileum. The response to venom (3 micrograms/ml) was not significantly affected by the histamine antagonist mepyramine (0.5 microM), or a preceding anaphylactic response. Mecamylamine, 5HT-desensitization or EXP3174 failed to have any significant effect on responses to venom (3 micrograms/ml). Responses to venom (3 micrograms/ml) were significantly inhibited by the cyclooxygenase inhibitor indomethacin (5 microM), the leukotriene D4 receptor antagonist FLP55712 (1 microM), the thromboxane A2 receptor antagonist GR32191B (1 microM), the muscarinic receptor antagonist atropine (10 nM) and the neurokinin-1 receptor antagonist CP96345 (0.1 microM). Venom (6 micrograms/ml) produced contractile responses in the rat isolated vas deferens which were abolished by the alpha 1-adrenoceptor antagonist prazosin (0.3 microM) and significantly potentiated by the neuronal uptake inhibitor DMI (1 microM). However, noradrenergic transmitter depletion with reserpine (5 mg/kg, i.p.) did not significantly inhibit responses to venom (6 micrograms/ml). Histamine fluorometric and phospholipase A2 assays failed to detect significant quantities of either substance in the venom. These results suggest that stonefish venom may cause the release of acetylcholine, substance P, and cyclooxygenase products, or contain components which act at these receptors. The venom also appears to contain a component which is a substrate for neuronal uptake and has a direct action at alpha 1-adrenoceptors.
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PMID:Pharmacological studies of stonefish (Synanceja trachynis) venom. 784 90

The studies described herein characterize animal behavioral models for conjunctival and cutaneous itch. Histamine was used as the reference stimulus for model development because it is firmly established as a pruritogen in both conjunctiva and skin. Itching evokes the desire to scratch in human subjects, so hind limb scratching at the afflicted area was used to identify pruritogenic stimuli. Under optimized environmental conditions, hind limb scratching behavior yielded substantial and highly reproducible responses. The conjunctival itch-scratch response was delineated from pain and foreign body sensations by using appropriate stimuli. Examination of a large and diverse variety of autocoids revealed that only histamine, platelet-activating factor (PAF) and arachidonic acid and its cyclooxygenase metabolite prostaglandin E2 possessed meaningful pruritogenic activity. PAF-induced ocular pruritus did not involve histamine release, according to studies with appropriate antagonists. Thus PAF-induced ocular pruritus was unaffected by the histamine H1-receptor antagonist pyrilamine but was substantially attenuated by the PAF antagonists WEB 2086 and CV-6209 and was virtually abolished by E-6123. Similar itch-scratch behaviors were quantified in hairless guinea pig skin following the application of cowhage or the iontophoretic administration of histamine and PAF. Findings from these newly developed itching models suggest that PAF could be an important mediator of the pruritic sensation by activating a population of nerve endings responsible for encoding the itch sensation.
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PMID:Characterization of a behavioral model for peripherally evoked itch suggests platelet-activating factor as a potent pruritogen. 785 91

Non-steroidal anti-inflammatory drugs have a direct action on spinal nociceptive processing in vivo with a relative order of potency which correlates with their capacity as inhibitors of cyclooxygenase activity. However, recent clinical surveys and new in vivo evidence strongly suggest that for some of these agents, centrally mediated analgesia may also be achieved by additional mechanisms, which are independent of prostaglandin synthesis inhibition. In this review we explore the likelihood for such mechanisms following an extensive survey of existing data. The implications of these mechanisms are discussed in the light of our current understanding of spinal nociceptive processing.
Pain 1994 Oct
PMID:Non-steroidal anti-inflammatory drugs and spinal nociceptive processing. 747 96

The 2'-deoxyribonucleoside cyanoboranes were effective anti-inflammatory agents in rodents at 2-8 mg/kg; they blocked induced edema, septic shock, and pleurisy. Overall compounds 3',5'-O-(bis- (triisopropylsilyl)-2'-deoxyinosine (1), 3',5'-O-bis(triisopropylsilyl)-2'-deoxycytidine (10), N3-(cyanoboryl)-2'-deoxycytidine (11), N7-(cyanoboryl)-N2-isobutyryl- 3',5'-O-bis(triisopropylsilyl)-2'-deoxyguanosine (20), and N7-(cyanoboryl)-N2- isobutyryl-5'-O-(4,4'-dimethoxytrityl)-3'-O-(triisopropylsilyl)-2' -deoxyguanosine (22) were the most active when all the anti-inflammatory screens are considered. The agents also blocked both local and central pain caused by inflammation. These nucleosides blocked calcium resorption but were less effective compared to other amine carboxyboranes. The inflammation process appeared blocked by these compounds because of their effectiveness in reducing both hydrolytic lysosomal enzyme and proteolytic enzyme activities. The agents were also dual inhibitors of prostaglandin cyclooxygenase and 5'-lipoxygenase activities in leukocytes and macrophages. These agents at 10(-4) M demonstrated no specific organ toxicity to ileum mucosa cells grown in tissue culture.
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PMID:Anti-inflammatory and anti-osteoporotic activities of base-boronated nucleosides and phosphate-boronated nucleotides in rodents. 788 56

Currently, the pharmacology of analgesics can be sum up to three main compounds: morphine, paracetamol and aspirin. The use of antidepressants and anticonvulsants will also be mentioned. Morphine remains the reference compound among centrally acting analgesics both for acute and chronic pain. Its mechanism of action is relatively well known as well as the role of opiate receptors. Paracetamol is largely used as analgesic for relief of slight to moderate pain. Its mechanism of action still remains unclear. Usually the tolerability of this compound is considered as being excellent. However overdosage can induce severe and possible lethal liver necrosis. Aspirin is also a very old and a largely used compound. Its inhibiting effect on cyclooxygenase acts mainly peripherally but it could also act centrally. According to the current knowledge of its mechanism of action, it seems that the main pharmacological properties as well as adverse events of aspirin are all related to its enzyme inhibiting effect. Slight to moderate pain, related or not to inflammatory disease responds well to aspirin and other NSAIDs.
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PMID:[Drugs for relief of pain]. 793 82

Calcitonin (CT) is a polypeptide hormone produced in the thyroid gland that regulates, blood calcium levels and bone calcium metabolism. The unexpected finding of binding sites for calcitonin in several areas of the brain oriented attention to activities of CT in the central nervous system and also to its antinociceptive action. The first report of this last effect was in 1975, and the many different experimental and clinical data on this topic reported since then are reviewed here. The heterogenous findings have been organized according to the logical classification of animal and human studies. For each of these headings, subheadings such as acute and chronic pain, different kinds of administration and different procedures used to record the results, are considered. The several proposed mechanisms of action, involving serotoninergic, catecholaminergic, Ca2+ fluxes, protein phosphorylation, beta-endorphin production, cyclooxygenase inhibition and histamine interference are also reviewed. Calcitonin, neurotensin, substance P, VIP and, recently, CGRP are some of the non-opioid peptides that have been reported to interfere with pain and that open up a new, alternative way of investigating antinociceptive drugs different than opioid or opioid-like agents. An examination of the state-of-investigation of calcitonin's antinociceptive activity in the last 17 years shows that many experimental studies indicate the existence of this effect, including studies in humans, and this opens up perspectives for therapy with a new class of antinociceptive agents.
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PMID:Calcitonin and its antinociceptive activity: animal and human investigations 1975-1992. 794 19

Tebufelone is a novel nonsteroidal anti-inflammatory drug (NSAID), of the di-tert-butylphenol (DTBP) class, which displays potent anti-inflammatory, analgesic and anti-pyretic properties in a variety of animal models. In this report, the effects of Tebufelone on arachidonic acid (AA) metabolism are reviewed. Tebufelone potently inhibits the formation of prostaglandins (PGE2) a key mediator of pain and inflammation, in isolated enzyme preparations (IC50 = 1.5 microM, KI = 0.35 microM), two in vitro cellular systems: rat peritoneal macrophages (IC50 = 0.02 microM) and human whole blood (IC50 = 0.08 microM), and ex vivo in man. In addition to PGE2 inhibition, which is common to all NSAIDs, higher concentrations of Tebufelone block the in vitro formation of products of the lipoxygenase pathway [leukotrienes (LTB4)] in rat macrophages (IC50 = 20 microM) and human whole blood (IC50 = 22 microM). Substrate incorporation studies (14C-AA) indicate that Tebufelone reversibly inhibits cyclooxygenase (CO) and 5-lipoxygenase (5-LO) enzymes rather than regulating the release of AA. Tebufelone was shown to be a more potent CO inhibitor than indomethacin and a less potent 5-LO inhibitor than RG-5901. Comparisons to structurally related compounds under development (E-5110, Esai; KME-4, Kanagafuchi), found Tebufelone to be the most potent CO inhibitor in vitro. All three DTBP compounds were equipotent 5-LO inhibitors. It is likely that Tebufelone's inhibitory effects on AA metabolism are, in part, responsible for its in vivo efficacy and enhanced safety profile.
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PMID:Effects of tebufelone (NE-11740), a new anti-inflammatory drug, on arachidonic acid metabolism. 794 23

The nonsteroidal anti-inflammatory drugs (NSAIDs) continue to be important for palliation of pain and decreasing inflammation and fever throughout the world. The literature over the past year has continued to broaden our understanding of the potential toxic events associated with the use of these agents. In addition, there have been interesting observations concerning their modes of action. In this article, studies describing the identification of two different isoforms of the prostaglandin synthase enzyme (cyclooxygenase) are reviewed, which might explain some of the observed differences in effects noted for the various available NSAIDs. Problems related to NSAID-induced renal dysfunction and hepatic events and gastroduodenal as well as large- and small-bowel effects of the NSAIDs are also considered.
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PMID:Actions and toxic effects of the nonsteroidal anti-inflammatory drugs. 806 Jul 59

Symptoms and disability vary considerably over time and among individuals with similar degrees of radiographic osteoarthritis. The results of recent clinical studies have reaffirmed that many patients prefer nonsteroidal anti-inflammatory drugs (NSAIDs) to analgesics while also demonstrating that many individuals who have been receiving NSAIDs can manage without them. Certain but as yet poorly characterized patients appear to respond more favorably to treatment with NSAIDs. Thus, both chronic unquestioning use of NSAIDs and denial of NSAIDs to individuals with osteoarthritis are extreme and inappropriate approaches to treatment. Concerns about the gastrointestinal toxicity of NSAIDs remain, although strategies to prevent this toxicity provide some reassurance and should be considered for use in individuals who are at particular risk. These strategies include the use of NSAIDs that are selective inhibitors of the prostaglandin endoperoxide synthase II isoenzyme and are potentially less ulcerogenic or the coprescription of prostaglandin analogues or other ulcer-healing drugs. The costs and benefits of such approaches have yet to be established. Cartilage metabolism is adversely affected by certain NSAIDs in vitro, but the relevance of these observations remains unclear. In our view, the judicious use of NSAIDs in the treatment of osteoarthritis is acceptably safe and indicated in individuals in whom pain cannot be managed by simple analgesics and nonpharmacologic approaches.
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PMID:Nonsteroidal anti-inflammatory drugs in the treatment of osteoarthritis. 806 16

Repetitive C afferent input evokes a facilitated state of processing that results in increased receptive fields and exaggerated responses to afferent input ("wind-up"). These phenomena underlie the behavioral phenomena of secondary hyperalgesia and this in turn is an important component of postoperative pain. The initiation of this facilitated component is not well blocked by even higher concentrations of volatile anesthetics, but it can be prevented by pretreatment with agents known to block afferent input (local anesthetics) or C-fiber transmitter release (opiates) or to act at one of several links to block a complex spinal cascade involving the N-methyl-D-aspartate receptor, nitric oxide synthase, and cyclooxygenase. These fundamental mechanisms promise to have an impact on the management of postoperative pain.
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PMID:The spinal pharmacology of facilitation of afferent processing evoked by high-threshold afferent input of the postinjury pain state. 809 39


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