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

Venous stasis is a situation encountered commonly in varicose disorders. The potential implications of this decrease in oxygen levels in terms of the status of the cells of the vein were assessed. When endothelial cells are subjected to hypoxia, there is stimulation of the cells which shows itself as increased synthesis of prostaglandins and of PAF (Platelet Activating Factor). The synthesis of these typical mediators of inflammation results from activation by the calcium of phospholipase A2 which releases the arachidonic acid of phospholipids and this increase in intracellular calcium results itself from a fall in efficacy of calcium pumps due to the fall in ATP caused by hypoxia. Thus the fall in oxygen leads to the production of mediators of inflammation which activate leucocytes and result in local micro-inflammation which can be very rapidly eliminated if the circulation is restored but which can also cause irreversible damage to the vein by changes in venous tissue due to activated leucocytes which release proteases and free radicals after having penetrated the intima of the vein. These processes offer an explanation for the histological changes seen in varicose veins and the onset of localised pain during the development of such disease.
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PMID:[The relation between venous stasis and the occurrence of pain]. 149 30

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

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

Intraarterial injection of histamine into the isolated perfused rabbit ear causes a reflex fall in mean arterial blood pressure by stimulation of perivascular pain receptors. This effect is reduced by a low concentration of indomethacin (1 microgram/ml). The histamine H1-receptor antagonist mepyramine (10 micrograms/ml) reduced the effect of histamine. However, it also reduced the effect of acetylcholine. The histamine H2-receptor antagonist cimetidine (3-10 micrograms/ml) did not reduce the effect of histamine. Exogenously applied phospholipase A2 did not stimulate pain receptors on its own but enhanced the algesic effect of histamine, acetylcholine or bradykinin. This enhancement was abolished by indomethacin. Prostacyclin also enhanced the effect of histamine. The results suggest that histamine releases prostaglandins (E-type and prostacyclin) which in turn render the 'pain receptors' more sensitive to histamine. This effect may be of importance in inflammatory pain in that the effect of algogens (including histamine) is enhanced by an increased phospholipase A2-mediated synthesis of prostaglandins. Not only endogenously activated phospholipase A2 is able to split off prostaglandin precursors followed by subsequent generation of prostaglandins but also exogenously administered phospholipase A2 is able to induce the release of pain-enhancing prostaglandins.
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PMID:Dependence of histamine-evoked nociception on prostaglandin release. 612 58

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

Idiopathic low back pain has confounded health care practitioners for decades. The cellular and neural mechanisms that lead to facet pain, discogenic pain, and sciatica are not well understood. To help elucidate these mechanisms, anesthetized New Zealand white rabbits were used in a series of neurophysiologic and neuroanatomic studies. These studies showed the following evidence in support of facet pain: an extensive distribution of small nerve fibers and endings in the lumbar facet joint, nerves containing substance P, high threshold mechanoreceptors in the facet joint capsule, and sensitization and excitation of nerves in facet joint and surrounding muscle when the nerves were exposed to inflammatory or algesic chemicals. Evidence for pain of disc origin included an extensive distribution of small nerve fibers and free nerve endings in the superficial annulus of the disc and small fibers and free nerve endings in adjacent longitudinal ligaments. Possible mechanisms of sciatica included vigorous and long lasting excitatory discharges when dorsal root ganglia were subjected to moderate pressure, excitation of dorsal root fibers when the ganglia were exposed to autologous nucleus pulposus, and excitation and loss of nerve function in nerve roots exposed to phospholipase A2.
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PMID:Mechanisms of low back pain: a neurophysiologic and neuroanatomic study. 902 Feb 16

A phase I study was performed to evaluate the maximum tolerated dose (MTD), safety profile and pharmacokinetic data with VRCTC-310, a natural product derived from purified snake venom fractions, with phospholipase A2 activity and inhibitory effects against human and murine tumor cell lines. Fifteen patients with refractory malignancies were entered after providing written informed consent. VRCTC-310 was administered as an intramuscular injection daily for 30 consecutive days. Doses were escalated from 0.0025 to 0.023 mg/kg. Toxicities included local pain at the injection site, eosinophilia, reversible diplopia and palpebral ptosis. Dose escalation was stopped at 0.023 mg/kg, when two patients had developed anaphylactoid reactions. Both cases had high VRCTC-310-specific IgG by EIA. MTD was 0.017 mg/kg and the recommended dose for phase II studies is 0.017 mg/kg. Stabilization was found in six patients.
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PMID:Phase I study of VRCTC-310, a purified phospholipase A2 purified from snake venom, in patients with refractory cancer: safety and pharmacokinetic data. 940 9

Envenomation by Thalassophryne nattereri fishes are an important medical problem in northeast of Brazil, causing in human victims considerable pain and edema followed by necrosis. Venom obtained from fresh captured specimens of this fish was tested in vitro or in animal models for a better characterization of its toxic activities. Intradermal injection of the venom in the foot pad of mice induced local edema and hemorrhage followed a few hours later by necrosis. Subcutaneous injection of the venom induced systemic effects consisting in jerking motions, paralysis of hind limbs, erection of hair, rotational movements and violent convulsions followed by death. Dead animals showed hyperemia of the small intestine and lungs. The venom showed distinct edematous, necrotizing and hemolytic activities, a low level of hemorrhagic, myotoxic and proteolytic activities and no detectable phospholipase A2 activity. SDS-PAGE analysis of the crude venom showed at least 17 components with the major band located around Mw = 19,000. Almost all proteins stained by amido black were also revealed by Western blotting with antibodies to T. nattereri venom. Fractionation of the venom by either gel filtration or cation exchange chromatography resulted in a few distinct peaks but in both situations the biological activities were located in only one of the peaks which corresponded to basic proteins with approximately Mw = 47,000. Heating of the venom at 56 degrees C for 60 min completely destroyed its biological activities. All venom toxic activities except edema were completely neutralized after in vitro incubation with anti-T. nattereri serum.
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PMID:Thalassophryne nattereri fish venom: biological and biochemical characterization and serum neutralization of its toxic activities. 962 May 88

The pathophysiologic mechanisms of painful radiculopathy caused by a herniated intervertebral disc remain unknown. This study sought to determine whether the autologous intervertebral disc produces pain related behavior and whether phospholipase A2 and nitric oxide are involved in the pathophysiologic mechanism producing the behavior. A rat model, in which autologous intervertebral discs were implanted on the nerve root in the lumbar spine, was used to measure hyperalgesia, which is a pain related behavior in the rat. In this experimental model, autologous nucleus pulposus and anulus fibrosus transplanted to lumbar nerve roots produced mechanical and thermal hyperalgesia, respectively. Epidural injection of a selective inhibitor for phospholipase A2 resulted in the disappearance of hypersensitivity to noxious mechanical stimuli. Thermal hyperalgesia produced by application of the anulus fibrosus was abated and abolished by epidural injections of saline and one of the inhibitors for nitric oxide synthase, respectively. The authors suggest that chemical mediators such as phospholipase A2 and nitric oxide, induced by extruded or sequestrated intervertebral discs, are involved in the pathophysiologic mechanisms of painful radiculopathy in lumbar disc herniations. This study may be useful in attempting to develop new medical approaches for treatments of lumbar disc herniation.
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PMID:Possible mechanism of painful radiculopathy in lumbar disc herniation. 964 68

The purpose of this study was to examine whether mRNA of interleukin-A2, interleukin-6, phospholipase A2, and nitric oxide synthase was expressed in the nerve root and dorsal root ganglion of an animal model in which exposure to the nucleus pulposus induced mechanical hyperalgesia, a pain-related behavior. Autologous nucleus pulposus obtained from coccygeal discs was relocated on the L4 and L5 lumbar nerve roots after partial laminectomy. The reflex response to noxious mechanical stimuli to the hindpaw was measured preoperatively and to 4 weeks postoperatively. With a reverse transcription-polymerase chain reaction technique, expression of interleukin-1beta, interleukin-6, phospholipase A2, and inducible nitric oxide synthase genes in the nerve root and dorsal root ganglion was observed at 1, 2, and 4 weeks postoperatively. Mechanical hyperalgesia was observed from 3 days to 2 weeks postoperatively. The expression of interleukin-1beta, phospholipase A2, and inducible nitric oxide synthase mRNAs increased after only 1 week. This increase was related to mechanical hyperalgesia. Expression of interleukin-6 was detected in the neural tissue over time. It is possible that interleukin-1beta, phospholipase A2, and inducible nitric oxide in the nerve root or dorsal root ganglion, or in both, produce sciatic pain in the early stage of herniation of the lumbar disc.
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PMID:mRNA expression of interleukins, phospholipase A2, and nitric oxide synthase in the nerve root and dorsal root ganglion induced by autologous nucleus pulposus in the rat. 1063 62


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