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

The effects of intrathecal administration of prostaglandins on pain responses in conscious mice were evaluated by using hot plate and acetic acid writhing tests. Prostaglandin D2 (0.5-3 ng/mouse) had a hyperalgesic action on the response to a hot plate during a 3-60 min period after injection. Prostaglandin E2 showed a hyperalgesic effect at doses of 1 pg to 10 ng/mouse, but the effect lasted shorter (3-30 min) than that of prostaglandin D2. Similar results were obtained by acetic acid writhing tests. The hyperalgesic effect of prostaglandin D2 was blocked by simultaneous injection of a substance P antagonist (greater than or equal to 100 ng) but not by AH6809, a prostanoid EP1-receptor antagonist. Conversely, prostaglandin E2-induced hyperalgesia was blocked by AH6809 (greater than or equal to 500 ng) but not by the substance P antagonist. Prostaglandin F2 alpha had little effect on pain responses. These results demonstrate that both prostaglandin D2 and prostaglandin E2 exert hyperalgesia in the spinal cord, but in different ways.
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PMID:Nociceptive effects induced by intrathecal administration of prostaglandin D2, E2, or F2 alpha to conscious mice. 232 44

Following four different surgical procedures in lambs 3-5 weeks old, plasma immunoreactive beta-endorphin (beta-EP) and cortisol were assayed at 15 min and 24 h as determinants of post-operative stress. A threefold increase in mean plasma beta-EP levels occurred 15 min after tail docking, and a maximal eight- to tenfold increase occurred in response to castration and/or mulesing with tail docking. Significant increments in mean plasma cortisol levels followed these surgical procedures with the maximal response 15 min after mulesing plus castration with tail docking. The physiologically active 'free' cortisol in plasma represents about 25% of the cortisol, as measured, and the two are highly correlated. At 24 h, beta-EP levels in all treated groups were similar to controls, although a small elevation in cortisol levels was still present in the lambs subjected to mulesing. Ultrafiltration of plasma extracts showed that peak beta-EP levels contained about 40% immunoreactivity from low molecular weight species (mol. wt less than 10,000). By specific radioimmunoassay and reverse-phase high-performance liquid chromatography this comprised about 75% beta-EP1-31, the most potent analgesic endorphin, 10% beta-EP1-27, and 15% alpha-N-acetyl-beta-EP. Increased beta-EP1-31 levels may modulate post-operative pain in lambs.
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PMID:Stress-induced changes in plasma concentrations of immunoreactive beta-endorphin and cortisol in response to routine surgical procedures in lambs. 297 99

1. Intrathecal (i.t.) administration of prostaglandin E2 (PGE2) to conscious mice was reported to induce allodynia, a state of discomfort and pain evoked by innocuous tactile stimuli through prostaglandin E receptor subtype EP1 and hyperalgesia through prostaglandin E receptor subtypes EP2 and/or EP3. In the present study, we investigated the effects of an EP1 antagonist on these sensory disorders by use of ONO-NT-012 or AH6809. 2. ONO-NT-012 dose-dependently antagonized the PGE2-induced allodynia but had no effect on the PGE2-induced hyperalgesia by the hot plate test. On the other hand, AH6809 blocked the PGE2-induced hyperalgesia at the highest dose examined (50 micrograms kg-1) but had no effect on the PGE2-induced allodynia. The i.t. injection of AH6809 or ONO-NT-012 alone did not have any effect on the response to noxious or innocuous stimuli. 3. Increasing doses (5 pg kg(-1)-500 ng kg-1) of ONO-NT-012 produced parallel shifts to the right of the dose-response curves to PGE2. The Schild plot regression line was linear and the slope was close to unity. The pA2 value against PGE2 was calculated to be 9.96. 4. The present study demonstrates that i.t. administration of PGE2 exerts allodynia through EP1 in the mouse spinal cord and that ONO-NT-012 is a highly potent, simple competitive antagonist for the PGE2-induced allodynia.
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PMID:Blockade by ONO-NT-012, a unique prostanoid analogue, of prostaglandin E2-induced allodynia in conscious mice. 764 86

1. Intrathecal (i.t.) administration of prostaglandin E2 (PGE2) to conscious mice induced allodynia, a state of discomfort and pain evoked by innocuous tactile stimuli, and hyperalgesia as assessed by the hot plate test. We characterized prostaglandin E receptor subtypes (EP1-3) involved in these sensory disorders by use of 7 synthetic prostanoid analogues. 2. Sulprostone (EP1 < EP3) induced allodynia over a wide range of dosages from 50 pg to 5 micrograms kg-1. The maximal allodynic effect was observed at 5 min after i.t. injection, and the response gradually decreased over the experimental period of 50 min. This sulprostone-induced allodynia showed a time course similar to that induced by PGE2. 3. 17-Phenyl-omega-trinor PGE2 (EP1 > EP3) and 16,16-dimethyl PGE2 (EP1 = EP2 = EP3) were as potent as PGE2 in inducing allodynia, and more potent than sulprostone. Butaprost (EP2), 11-deoxy PGE1 (EP2 = EP3), MB 28767 (EP3), and cicaprost (prostaglandin I2 (IP-) receptor) induced allodynia, but with much lower scores. 13,14-Dihydro-15-keto PGE2, a metabolite of PGE2, did not induce allodynia. 4. 16,16-Dimethyl PGE2 as well as PGE2 induced hyperalgesia over a wide range of dosages (16,16-dimethyl PGE2: 5 pg-0.5 micrograms kg-1 PGE2: 50 pg-0.5 micrograms kg-1) with two apparent peaks at 0.5 ng kg-1 and 0.5 micrograms kg-1. Sulprostone (EP1 < EP3) and 17-phenyl-omega-trinor PGE2 (EP1 > EP3) showed a bell-shaped hyperalgesia at lower doses of 5 pg-5 ng kg-1 and 50 pg-50 ng kg-1, respectively. MB28767 (EP3)showed a monophasic hyperalgesic action over a wide range of dosages at 50 pg-S5 Microg kg-1. Butaprost(EP2) induced hyperalgesia at doses higher than 50 ng kg-1.5. These results demonstrate that PGE2 may exert allodynia through the EP1-receptor and hyperalgesia through EP2- and EP3-receptors in the mouse spinal cord.
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PMID:Characterization of EP-receptor subtypes involved in allodynia and hyperalgesia induced by intrathecal administration of prostaglandin E2 to mice. 792 97

We recently reported that intrathecal (i.t.) administration of prostaglandin E2 (PGE2) to conscious mice induced allodynia, a state of discomfort and pain evoked by innocuous tactile stimuli. In the present study, we examined the effect of the PGE receptor EP1 subtype antagonist ONO-NT-012, the N-methyl-D-aspartate (NMDA) receptor antagonist MK-801, and the NO synthase inhibitor N omega-nitro-L-arginine methyl ester (L-NAME) on the allodynia. The PGE2-induced allodynia was blocked by simultaneous i.t. injection of ONO-NT-012, MK-801, or L-NAME. However, 5 min after i.t. injection of PGE2, the allodynia was significantly blocked by i.t. L-NAME, but not by i.t. ONO-NT-012 or MK-801. These results demonstrate that the PGE2-induced allodynia, once developed, does not require the continued agonist occupancy of EP1 and NMDA glutamate receptor sites.
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PMID:L-NAME, an inhibitor of nitric oxide synthase, blocks the established allodynia induced by intrathecal administration of prostaglandin E2. 878 49

Topically administered ketorolac (Acular), a cyclooxygenase inhibitor, has recently been reported as clinically beneficial for treating allergic conjunctivitis. The ability of ketorolac to relieve the itching associated with allergic conjunctivitis is intriguing because cyclooxygenase inhibitors are not regarded as useful in treating allergic dermatoses and prostaglandins (PG) do not elicit an itch response in human skin. To gain further insight into the mechanisms involved in the antipruritic activity of ketorolac, we used a method of reproducibly assessing ocular surface itch responses in the guinea pig. The measurement of conjunctival pruritus involved a recently developed behavioral model whereby hind limb scratching episodes directed toward the afflicted area were quantified. Itch-scratch episodes have previously been delineated from foreign body and pain sensations, which do not evoke such a behavioral response. Ketorolac significantly inhibited the itching associated with experimental allergic conjunctivitis. The basis of this antipruritic activity may be ascribed to preventing the biosynthesis of itch-producing PGs because ketorolac inhibited arachidonic acid-induced pruritus. In contrast to skin studies, PGE2 and PGI2 were found to be potent pruritogens at the guinea pig ocular surface. PGD2 was a weak pruritogen, and PGF2 alpha and the thromboxane-mimetic U-46619 produced no meaningful response. Further studies involving selective agonists and antagonists suggested that EP1 receptors, IP receptors and PGD2-sensitive receptors may mediate prostanoid-induced conjunctival itching. No evidence for the involvement of other prostanoid receptor subtypes was obtained. Although the EP1 receptor antagonist AH 6809 and the DP receptor antagonist BW A868C inhibited PGE2- and PGD2-induced itching, respectively, neither antagonist alone significantly affected the itching associated with experimental allergic conjunctivitis. A combination of AH 6809 and BW A868C, however, did exhibit antipruritic activity. It appears that for effective relief of itching in allergic conjunctivitis, it is not sufficient to block the effects of a single pruritogenic PG. It is preferable to reduce the participation of all pruritogenic PGs by either using combined receptor antagonists or by using a cyclooxygenase inhibitor such as ketorolac to block their biosynthesis.
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PMID:Characterization of receptor subtypes involved in prostanoid-induced conjunctival pruritus and their role in mediating allergic conjunctival itching. 885 86

The effects of microinjection of prostaglandin E2 (PGE2) (0.5 fg-500 pg/0.2 microl) into the medial part of the preoptic area (MPO) on nociception were studied using a hot-plate test in rats. The intraMPO microinjection of PGE2 only at non-pyrogenic doses (5-50 fg) reduced the paw-withdrawal latency, suggesting hyperalgesia. Maximal reduction was obtained 15 min after the injection of PGE2 at 50 fg. Subsequently, to determine which types of prostanoid receptors are involved in the hyperalgesic effect of PGE2 in the MPO, we administered PGE2 receptor agonists, i.e., 17-phenyl-omega-trinor PGE2 (an EP1 receptor agonist), butaprost (an EP2 receptor agonist) and M&B28767 (an EP3 receptor agonist) into the MPO and observed the nociceptive behavior. The intraMPO injection of M&B28767 (0.005 fg-50 pg), like that of PGE2, exhibited a U-shaped dose response characteristic, i.e., a significant decrease of the paw-withdrawal latency only at 0.05-5 fg with the maximal response at 0.5 fg. However, neither the administration of EP1 (0.5 fg-50 ng) nor EP2 (0.5 fg-500 pg) agonists had any effect on nociception. The microinjection of M&B28767 at 0.5 fg into the other parts of preoptic hypothalamus (the lateral part of the preoptic area and the median preoptic nucleus) and the diagonal band of Broca (DBB) produced hyperalgesia similar to the intraMPO-induced hyperalgesia in terms of magnitude and time course. Microinjection of M&B28767 (0.5 fg) into either the paraventricular nucleus, the ventromedial hypothalamus, the lateral hypothalamic area or the septal nucleus had no effect on nociception. These findings suggest that PGE2 at non-pyrogenic doses in the brain induces hyperalgesia, at least in part, through its actions on EP3 receptors in the preoptic hypothalamus and the DBB in rats.
Pain 1997 Jul
PMID:Prostaglandin E receptor EP3 subtype is involved in thermal hyperalgesia through its actions in the preoptic hypothalamus and the diagonal band of Broca in rats. 923 74

This review summarizes our studies on the molecular biology of prostaglandin (PG) receptors and L-histidine decarboxylase (HDC). Regarding PG receptors, we have cloned five basic PG receptors (DP, EP, FP, IP, TP) and four EP subtypes (EP1-EP4). The PG receptors are divided into three families related to signal transduction systems of the receptors; Gs-couple group (IP, DP, EP2 and EP4), Gq-couple group (TP, FP and EP1), and Gi-couple group (EP3 and its isoform). EP3 isoforms having different C-terminal peptides can couple to distinct G proteins (Gi, Gs, Gq). Tissue specific expression of EP subtype mRNAs was observed in various organs. The phenotypic changes of mice deficient in each receptor are; the abnormal labor in FP-deficient mice, the failure of febrile response in EP3-deficient mice, the abnormal closure of ductus arteriosus after birth in EP4-deficient mice, and the impaired inflammatory swelling and pain responses in IP-deficient mice. Regarding HDC, we have purified mouse HDC from mastocytoma cells, which is a dimer of 53 kDa subunit, and then cloned its cDNA. The size of a cDNA-deduced HDC is 74 kDa. In the rat mast cell line, the endogenous 74 kDa form of HDC was translated in the cytosol and then translocated to the ER, where it was post-translationally processed to the 53 kDa form. On the other hand, the cytosolic 74 kDa form was rapidly degraded by an ATP/ubiquitin-dependent proteasome system. The 74 kDa form without on N-terminal signal sequence is inserted into the ER membrane with a C-terminal segment.
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PMID:[Molecular biology of prostaglandin receptor and L-histidine decarboxylase]. 1051 17

The hypothesis that prostaglandins contribute to hyperalgesia resulting from nerve injury was tested in rats in which the sciatic nerve was partially transected on one side. Subcutaneous injection of indomethacin (a classic inhibitor of cyclo-oxygenase) into the affected hindpaw relieved mechanical hyperalgesia for up to 10 days after injection. Subcutaneous injection of meloxicam or SC-58125 (selective inhibitors of cyclo-oxygenase-2) into the affected hindpaw also relieved mechanical hyperalgesia, but with a shorter time-course. Subcutaneous injection of SC-19220 (an EP1 prostaglandin receptor blocker) into the affected hindpaw produced significant relief of mechanical and thermal hyperalgesia. Comparable injections into the contralateral paw or abdomen had no effect on mechanical or thermal hyperalgesia, suggesting that the effects we observed were local rather than systemic. We conclude that prostaglandins, probably prostaglandin E1 or E2, contribute to the peripheral mechanisms underlying hyperalgesia following nerve injury. These data provide further evidence that inflammatory mediators contribute to neuropathic pain, and may warrant further study of peripherally administered non-steroidal anti-inflammatory drugs as a possible treatment for such pain in patients.
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PMID:Hyperalgesia due to nerve injury: role of prostaglandins. 1057 19

The lipid mediator prostaglandin E2 (PGE2) has diverse biological activity in a variety of tissues. Four different receptor subtypes (EP1-4) mediate these wide-ranging effects. The EP-receptor subtypes differ in tissue distribution, ligand-binding affinity, and coupling to intracellular signaling pathways. To identify the physiological roles for one of these receptors, the EP1 receptor, we generated EP1-deficient (EP1-/-) mice using homologous recombination in embryonic stem cells derived from the DBA/1lacJ strain of mice. The EP1-/- mice are healthy and fertile, without any overt physical defects. However, their pain-sensitivity responses, tested in two acute prostaglandin-dependent models, were reduced by approximately 50%. This reduction in the perception of pain was virtually identical to that achieved through pharmacological inhibition of prostaglandin synthesis in wild-type mice using a cyclooxygenase inhibitor. In addition, systolic blood pressure is significantly reduced in EP1 receptor-deficient mice and accompanied by increased renin-angiotensin activity, especially in males, suggesting a role for this receptor in cardiovascular homeostasis. Thus, the EP1 receptor for PGE2 plays a direct role in mediating algesia and in regulation of blood pressure.
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PMID:The prostaglandin E2 EP1 receptor mediates pain perception and regulates blood pressure. 1116 Jan 56


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