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)

Carbohydrate intolerance to lactose is widely accepted as a cause of gastrointestinal symptoms, but controversy persists on how important dietary fructose intolerance (DFI) is in causing gastrointestinal pain and suffering and if an elimination diet can control the presenting complaints. The objective of this study was to identify a group of well-defined DFI patients and explore whether dietary education followed by dietary compliance could control symptoms and improve quality of life. During a 5-year period, patients referred to a pancreato-biliary clinic were evaluated for dietary carbohydrate intolerances if they presented with gastrointestinal pain and/or gas and/or bloating and/or diarrhea. Patients were tested with a standardized mixture of glucose, fructose, and lactose diluted in sterile water. End-expiratory breath samples were collected for hydrogen and methane measurement. Symptoms were scored using a 9-point symptom questionnaire. The patients underwent in-depth education by a dietician, and were provided with access to a cookbook, a newsletter, and a support group. A dietary questionnaire was used to evaluate compliance with the fructose-restricted diet. DFI can cause significant gastrointestinal symptoms that may not respond to medications or surgical interventions. Symptoms can improve and self-rated health does improve in DFI patients willing to adhere to a low fructose diet.
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PMID:Dietary fructose intolerance: diet modification can impact self-rated health and symptom control. 1562 40

Geranium niveum S. Watson (Geraniaceae) is a medicinal herb widely used by the Tarahumara Indians of Mexico. This species is rich in proanthocyanidins and other phenolics. Previous in vitro assays have demonstrated that proanthocyanidins exhibited antiinflammatory, antiviral, antibacterial, enzyme-inhibiting, antioxidant, and radical-scavenging properties. In view of its medicinal use and chemical composition, the aim of the present study was to determine the in vitro antioxidant activity of the extracts and two proanthocyanidins (geranins A and D) from the roots of G. niveum by using seven different assay systems, namely, 2,2'-azino-bis(3-ethylbenzthiazoline-6-sulfonic acid) (ABTS), 1,1-diphenyl-2-picrylhydrazyl (DPPH), superoxide anion (O2*-), hydrogen peroxide (H2O2), hydroxyl radical (OH*), hypochlorous acid (HOCl), and singlet oxygen ((1)O2). Two known antioxidants, resveratrol and ascorbic acid, were used as positive controls. The results showed that geranins A and D and the extracts were able to scavenge ABTS, DPPH, O2*-, OH*, and HOCl. The scavenging ability of geranins A and D was similar to that of resveratrol and ascorbic acid in the following assays: ABTS, O2*-, and HOCl. The scavenging capacity of ascorbic acid for DPPH was higher than that of both geranins and resveratrol. On the other hand, the OH* scavenging action of both geranins and resveratrol was similar. The methanol-CHCl3 (1:1) extract had a higher ability to scavenge ABTS, DPPH, and O2*- radicals than the chloroform extract. In turn, the latter was more potent than the methanol-CHCl3 (1:1) extract as OH* or HOCl scavenger agent. Neither geranins A and D nor the extracts were able to scavenge H2O2 and (1)O2. In conclusion, G. niveum roots have proanthocyanidins with powerful radical scavenging in vitro activity. This property may partially explain the wide use of this plant in the Tarahumara indigenous system of medicine for the treatment of gastrointestinal illnesses (other than spasms), pain, and fevers associated with oxidative stress.
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PMID:Antioxidant activity of A-type proanthocyanidins from Geranium niveum (Geraniaceae). 1576 26

Three experiments were conducted in order to investigate the possible involvement of the reactive oxygen species in the nociception within the subnucleus caudalis of the spinal trigeminal nucleus (Vc). In the first experiment the extracellular level of hydrogen peroxide was evaluated by microdialysis in the Vc of two groups of six rats before and after a formalin (group 1) or saline solution (group 2) injection into the upper lip. In the second experiment the formalin test was conducted in three groups of 6 rats after a microinjection of 2-methoxyestradiol (2-ME, a superoxide-dismutase inhibitor; group 1) or N-acetylcysteine (NAC, an oxygen intermediate scavenger; group 2) or saline solution (group 3) into the Vc. In the third experiment an histochemical assay for superoxide dismutase activity was performed on two groups of 4 rats each 2 h after a formalin (group 1) or saline solution (group 2) injection into the upper lip. The results showed that (1) the level of hydrogen peroxide increases into the Vc during facial pain (134% of baseline); (2) the inhibition of superoxide dismutase or the removal of oxygen intermediate within the Vc decreases the sensibility to facial pain stimuli; and (3) persistent facial pain stimuli decrease the superoxide activity into the Vc (90% of counter-lateral). These data indicate that reactive oxygen species are produced in the Vc during persistent facial pain and are necessary for the transmission of pain.
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PMID:Trigeminal pain transmission requires reactive oxygen species production. 1597 88

For over 50 years, acetaminophen (paracetamol) has been a staple in industrialized and non-industrialized countries for the treatment of pain and fever. Although its precise mechanisms of action are not known, the drug generates dose-dependent reduction in circulating prostaglandins, inhibits myeloperoxidase and the oxidation of lipoproteins, and appears to confer cardioprotection by blocking the effects of hydroxyl radical, peroxynitrite, and hydrogen peroxide. The drug might inhibit cyclooxygenase, although its ultimate target(s) is (are) still unclear. Sadly, since most investigations of acetaminophen have focused on its analgesic/antipyretic properties and hepatotoxicity, the effects of the drug on other mammalian organ systems, including the heart and circulation, have been ignored. Recently, work in our laboratory has shown acetaminophen to have a protective role in the injured mammalian myocardium. The cardioprotection was first observed in isolated, perfused guinea pig hearts subjected to ischemia-reperfusion injury. Hearts pretreated with acetaminophen recovered greater ventricular function and exhibited improved myofibrillar ultrastructure when compared to vehicle-treated hearts. More recent in vitro investigations have suggested protective roles for acetaminophen in barbiturate-induced arrhythmogenesis and myocardial hypoxia-reoxygenation injury. We have also extended our work to the in vivo arena. There, we found that acetaminophen reduced infarct size in dogs exposed to 60 minutes regional myocardial ischemia and 180 minutes reperfusion. We invite and encourage readers of this review to repeat/duplicate our experiments. Such work is needed to either challenge or support our findings. Further, more clinically-relevant work depends on these basic and related translational experiments.
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PMID:An old drug with a new purpose: cardiovascular actions of acetaminophen (paracetamol). 1624 34

Increasing evidence supports a possible role for nitric oxide (NO) in the transmission of pain signals and in the development of central mechanisms of hyperalgesia. Previously, we have shown that nitroglycerin, an NO donor, is able to induce a long-lasting hyperalgesic state in rats. Nitroglycerin-induced hyperalgesia can be detected as an increase in the nociceptive behavior evoked by the formalin test. In the present study we investigated the possible mediators in the nitroglycerin-induced hyperalgesic state. Male Sprague-Dawley rats were injected with nitroglycerin and pretreated with indomethacin, 5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclo-hepten-5,10-imine hydrogen maleate (MK-801) or N(omega)-nitro-L-arginine methyl ester (L-NAME). The results obtained showed that inhibition of prostaglandins or NO synthesis prevents nitroglycerin-induced hyperalgesia in Phase II of the formalin test. A similar inhibitory effect was also observed following pretreatment with the glutamate antagonist MK801. The present findings point to the role of prostaglandins, NO synthesis and glutamate activity in the induction of nitroglycerin-induced hyperalgesia.
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PMID:Prostaglandins, glutamate and nitric oxide synthase mediate nitroglycerin-induced hyperalgesia in the formalin test. 1650 4

As research techniques in wound care management improve, treatment protocols for the care of wounds must also change to ensure safe and optimal healing. In this study, I surveyed current practices of athletic trainers regarding the care of athletic wounds and compared the findings to current literature. I contacted 501 athletic trainers, including all NATA curricular undergraduate directors. Overall response rate was 58%; 78% of the athletic trainers from the curricular schools responded. Wet-to-dry, irrigation, and soaks were the three most common methods used to debride and cleanse a wound. Povidone-iodine (Betadine) and hydrogen peroxide were the two most popular cleansing agents. Conventional gauze was the primary dressing used by 67% of the athletic trainers, while 20% of those surveyed used occlusive dressings. Although povidone-iodine and hydrogen peroxide are commonly used, both are toxic to cells involved in the wound-healing process and delay healing. Research indicates that the best method of cleansing and debriding a wound is to irrigate it with saline. Occlusive dressings have a lower infection rate, are viral barriers, and are associated with faster wound healing and less pain than gauze dressings. Athletic trainers need to assess their wound care protocols so that they give the best possible care to their athletes.
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PMID:Wound care management: proper protocol differs from athletic trainers' perceptions. 1655 65

Prostaglandin H2 synthase (PGHS) synthesizes PGH2, a prostaglandin precursor, from arachidonic acid and was the first monotopic enzyme to have its structure experimentally determined. Both isozymes of PGHS are inhibited by nonsteroidal antiinflammatory drugs, an important class of drugs that are the primary means of relieving pain and inflammation. Selectively inhibiting the second isozyme, PGHS-2, minimizes the gastrointestinal side-effects. This had been achieved by the new PGHS-2 selective NSAIDs (i.e., COX-2 inhibitors) but it has been recently suggested that they suffer from additional side-effects. The design of these drugs only made use of static structures from x-ray crystallographic experiments. Investigating the dynamics of both PGHS-1 and PGHS-2 using classical molecular dynamics is expected to generate new insight into the differences in behavior between the isozymes, and therefore may allow improved PGHS-2 selective inhibitors to be designed. We describe a molecular dynamics protocol that integrates PGHS monomers into phospholipid bilayers, thereby producing in silico atomistic models of the PGHS system. Our protocol exploits the vacuum created beneath the protein when several lipids are removed from the top leaflet of the bilayer. The protein integrates into the bilayer during the first 5 ns in a repeatable process. The integrated PGHS monomer is stable and forms multiple hydrogen bonds between the phosphate groups of the lipids and conserved basic residues (Arg, Lys) on the protein. These interactions stabilize the system and are similar to interactions observed for transmembrane proteins.
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PMID:A computational protocol for the integration of the monotopic protein prostaglandin H2 synthase into a phospholipid bilayer. 1663 99

Molecular mechanisms underlying diabetes-induced painful neuropathy are poorly understood. We have demonstrated, in rats with streptozotocin-induced diabetes, that mechanical hyperalgesia, a common symptom of diabetic neuropathy, was correlated with an early increase in extracellular signal-regulated protein kinase (ERK), p38, and c-Jun N-terminal kinase (JNK) phosphorylation in the spinal cord and dorsal root ganglion at 3 weeks after induction of diabetes. This change was specific to hyperalgesia because nonhyperalgesic rats failed to have such an increase. Immunoblot analysis showed no variation of protein levels, suggesting a post-translational regulation of the corresponding kinases. In diabetic hyperalgesic rats, immunocytochemistry revealed that all phosphorylated mitogen-activated protein kinases (MAPKs) colocalized with both the neuronal (NeuN) and microglial (OX42) cell-specific markers but not with the astrocyte marker [glial fibrillary acidic protein (GFAP)] in the superficial dorsal horn-laminae of the spinal cord. In these same rats, a 7-day administration [5 microg/rat/day, intrathecal (i.t.)] of 1,4-diamino-2,3-dicyano-1,4-bis(2-aminophenylthio)butadiene (U0126), 4-(4-fluorophenyl)-2-(4-methylsulfinylphenyl)-5-(4-pyridyl)1H-imidazole (SB203580), and anthra(1,9-cd)pyrazol-6(2H)-one (SP600125), which inhibited MAPK kinase, p38, and JNK, respectively, suppressed mechanical hyperalgesia, and decreased phosphorylation of the kinases. To characterize the cellular events upstream of MAPKs, we have examined the role of the NMDA receptor known to be implicated in pain hypersensitivity. The prolonged blockade of this receptor during 7 days by (5R, 10S)-(+)-5-methyl-10, 11-dihydro-5H-dibenzo[a,d]-cyclohepten-5-10-imine hydrogen maleate (MK801; 5 microg/rat/day, i.t.), a noncompetitive NMDA receptor antagonist, reversed hyperalgesia developed by diabetic rats and blocked phosphorylation of all MAPKs. These results demonstrate for the first time that NMDA receptor-dependent phosphorylation of MAPKs in spinal cord neurons and microglia contribute to the establishment and longterm maintenance of painful diabetic hyperalgesia and that these kinases represent potential targets for pain therapy.
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PMID:Diabetes-induced mechanical hyperalgesia involves spinal mitogen-activated protein kinase activation in neurons and microglia via N-methyl-D-aspartate-dependent mechanisms. 1686 81

The aim of the present study was to determine whether there is a convergence of inputs from tooth pulp (TP) and the superior sagittal sinus (SSS) on rat C1 spinal neurons, and to examine the effects of iontophoretically applied N-methyl-D: -aspartate (NMDA) and non-NMDA receptor antagonists on the SSS-evoked activity of C1 neurons. Extracellular single unit-recordings were made from 20 C1 units responding to TP electrical stimulation with a constant temporal relationship to a digastric electromyogram signal, using a multibarrel electrode in pentobarbital-anesthetized rats. Ninety percent of C1 neurons (18/20) responding to TP stimulation also responded to the SSS stimulation. These neurons were considered to be SSS-afferent inputs from Adelta-fibers (5.8 +/- 0.6 m/s; n = 18), based on the calculation of nerve conduction velocity. After the iontophoretic application (30, 50, and 70 nA) of an NMDA receptor blocker (5R-10S)-(+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d] cycloheptene-5,10-imine hydrogen maleate (MK801) or a non-NMDA receptor blocker (6-cyano-7-nitroquinoxaline-2,3-dione) (CNQX), the mean number of spikes responding to the SSS stimulation significantly decreased (30, 50, and 70 nA; P < 0.05). These results suggest that there is a convergence of inputs from SSS and TP afferents on C1 neurons; it is possible that both NMDA and non-NMDA receptors located on C1 neurons may be targets for the treatment of the trigeminal referred pain associated with migraine.
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PMID:N-methyl-D-aspartate (NMDA) and non-NMDA receptor antagonists suppress the superior sagittal sinus-evoked activity of C1 spinal neurons responding to tooth pulp electrical stimulation in rats. 1699 14

Glioblastoma patients receive anti-inflammatory agent for alleviation of vasogenic edema and pain prior to surgery, radiotherapy, and chemotherapy. Oxidative stress is an important mechanism of action of some chemotherapeutic agents in the treatment of glioblastoma. So, we examined the modulatory effects of methylprednisolone (MP, a steroidal anti-inflammatory agent) and indomethacin (IM, a non-steroidal anti-inflammatory agent) on apoptosis in rat C6 glioblastoma cells following oxidative stress with hydrogen peroxide (H(2)O(2)). Exposure of C6 cells to 1 mM H(2)O(2) for 24 h caused significant amounts of morphological and biochemical features of apoptosis. Expressions of Bax and Bcl-2 at mRNA and protein levels were altered resulting in an increase in Bax : Bcl-2 ratio in apoptotic cells, which also exhibited overexpression of 80 kDa calpain and an increase in calpain-cleaved 145 kDa alpha-spectrin breakdown product. Immunofluorescent and propidium iodide labeling detected caspase-3-p20 fragment in apoptotic cells, indicating activation of caspase-3 as well. Treatment of cells with 1 microM MP or 10 microM IM alone did not induce apoptosis. Pretreatment (1 h) with either 1 microM MP or 10 microM IM significantly inhibited H(2)O(2) mediated apoptosis in C6 cells. Thus, pretreatment of glioblastoma with an anti-inflammatory agent, either steroidal or non-steroidal, may compromise the action of a chemotherapeutic agent that mediates therapeutic action via oxidative stress.
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PMID:Methylprednisolone and indomethacin inhibit oxidative stress mediated apoptosis in rat C6 glioblastoma cells. 1757 61


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