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)

Effects of pentobarbital and ether anesthesia on PGD2 contents in brain and plasma levels of compound beta, A.C.TH. epinephrine (E) norepinephrine (NE) and dopamine were investigated in 39 male Wistar strain rats weighing 280-300 g. They were divided into 3 groups: pentobarbital anesthesia group (P.A.), ether anesthesia group (E.A.) and control. Anesthesia or not the rats were decapitated the heads were frozen with liquid nitrogen and PGD2 were extracted and assayed by radioimmunoassay. In the group of P.A. and E.A., PGD2 contents of the brain were decreased by 69.6% and 77.8% of the control group respectively. In the group PA, plasma levels of Comp-beta, ACTH, E and NE were significantly decreased. In the EA group, plasma levels of Comp-beta was not changed but that of ACTH, E and NE were significantly increased. In the EA and PA groups, plasma levels of dopamine were not significantly changed. Intraventricularly injected PGD2 has been reported to induce the natural sleep in rat, increase or decrease the pain threshold and lower the body temperature in rat. On the other hand, intravenous injection of PGD2 has been reported to prolong the duration of pentobarbital anesthesia in rat or changed the EEG pattern to slow wave in cat. Stresses including restrain and foot shock have been reported to increase the PGE2 and PGF2a in the brain of rat. The present findings demonstrate that pentobarbital and ether anesthesia decreased the PGD2 contents in the brain of rat.
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PMID:The effect of pentobarbital and ether anesthesia on rat brain PGD2 content. 261 Feb 92

A mode of interaction of bradykinin with prostaglandins (PGs) in pain were compared with that in acute inflammation. When pain production was measured as an increase in reflex hypertensive response of the lightly anesthetized dogs after intrasplenic injection of bradykinin, the response was dependent to the doses (0.3-5 nmol) of bradykinin and that by the small doses (0.1-1 nmol) was blocked by intrasplenic infusion of indomethacin (0.54 mumol/min). The response to the threshold dose of bradykinin (0.3 nmol), which was suppressed during the indomethacin infusion, was potentiated by simultaneous injection of exogenous PGs. Order of the potency was PGI2 greater than PGH2 greater than PGE2 = TXA2 much greater than PGD2. Thus, it is clear that bradykinin induced pain through the generation of one of prostaglandins. On the other hand, the activity of bradykinin in plasma leakage was potentiated by simultaneous injection of PGE2, when tested in rabbit skin. In rat carrageenin-induced pleurisy, plasma prekallikrein was activated and high molecular weight (HMW) kininogen, not low molecular weight (LMW) kininogen, was consumed in the pleural cavity in the entire course of the pleurisy. Bradykinin played a role in plasma exudation in the pleurisy, because the plasma leakage was markedly inhibited in the rats, in which prekallikrein and HMW kininogen in plasma were depleted by intravenous bromelain. PGE2 was found in the pleural exudate, but the contribution of PGE2 itself to the plasma exudation seems to be only 10%. On the basis of the bradykinin release in the pleural cavity, once the PGE2 release was superimposed, the maximal plasma leakage was observed, indicating that PGE2 was released independently from bradykinin, and potentiated the plasma leakage by bradykinin.
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PMID:Different modes of interaction of bradykinin with prostaglandins in pain and acute inflammation. 381 4

Aerosolized prostacyclin (PGI2) potentiated the increase in pulmonary resistance to inflation induced by serotonin, prostaglandin F2 alpha (PGF2 alpha), acetylcholine and histamine in the guinea-pig. This was not due to a reflex, nor to further production of PG cyclooxygenase derivatives. PGI2 and PGF2 alpha induced contraction of the parenchyma lung strip of the guinea-pig, which could be inhibited by polyphloretin phosphate and by PGE1. Since PGF2 alpha failed to potentiate the bronchial responses to acetylcholine, histamine or serotonin, under conditions where PGI2 was effective, the in vitro similarities between the two PGs cannot explain the in vivo results. The ability of PGI2 to potentiate bronchial responses was not shared by the other PGs. Since the latter are either bronchoconstrictor agents by themselves (PGF2 alpha and PGD2), or bronchodilators (PGE1, PGE2), our hypothesis is that PGI2 potentiates the responses of the bronchi to various agonists by a mechanism similar to that which accounts for the potentiation of acute inflammation and pain by PGE1 and PGE2, the latter being ineffective in enhancing the bronchial responses because of the associated bronchodilator activity.
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PMID:Enhancement by prostacyclin of the contractility of the guinea-pig airways smooth muscle. 703 89

We recently reported that intrathecal (i.t) administration of prostaglandin (PG) F2 alpha to conscious mice induced allodynia that was elicited by non-noxious brushing of the flanks. In the presents study, we demonstrate that i.t. administration of PGD2 and PGE2 to conscious mice also results in allodynia. Dose dependency of PGD2 for allodynia showed a skewed bell-shaped pattern (0.1 ng-2.5 micrograms/mouse), and the maximal allodynic effect was observed with 1.0 microgram at 15 min after intrathecal injection. PGD2-induced allodynia showed a time course and dose dependency similar to that induced by PGF2 alpha, but with lower scores. On the other hand, dose dependency of PGE2 for allodynia showed a bell-shaped pattern over a wide range of dosage from 10 fg to 2.0 micrograms/mouse. The maximal allodynic effect was observed with 0.01-0.1 microgram at 5 min after i.t. injection, and the response gradually decreased over the experimental period of 50 min. Intrathecally administered strychnine and the GABAA antagonist bicuculline also induced allodynia in conscious mice. The time courses of allodynia evoked by strychnine and bicuculline coincided with those by PGE2 and PGF2 alpha, respectively. PGE2-induced allodynia was dose-dependently relieved by the strychnine-sensitive glycine receptor agonist taurine, the NMDA receptor antagonist ketamine, and a high dose of the alpha 2-adrenergic agonist clonidine, but not by the GABAA agonist muscimol or by the GABAB agonist baclofen. In contrast, PGF2-induced allodynia was dramatically inhibited by clonidine and baclofen, but not by taurine, ketamine or muscimol.(ABSTRACT TRUNCATED AT 250 WORDS)
Pain 1994 May
PMID:Allodynia evoked by intrathecal administration of prostaglandin E2 to conscious mice. 791 52

The therapeutic utility of cyclooxygenase (CO) inhibitors, such as ketorolac, in reducing the inflammatory events associated with allergic conjunctivitis is not unexpected since prostanoids (PG) elicit conjunctival redness (PGD2, PGE2, PGF2 alpha), edema (PGD2, TxA2), eosinophil infiltration (PGD2, PGJ2) and mucous cell discharge (PGD2, PGJ2, TxA2). Recently, topically administered ketorolac has also been reported to alleviate the itching associated with allergic conjunctivitis. This was viewed as intriguing since CO inhibitors are not regarded as useful for treating itching dermatoses and PGs do not elicit itching when applied to the skin. In order to investigate the antipruritic activity of ketorolac, we developed a model for reproducibly measuring ocular surface itch responses. The model involves itch-scratch responses to pruritogens applied locally to the ocular surface. Painful and foreign body stimuli do not produce an itch-scratch response. Unlike reported skin studies, PGE2 was a potent itch-producing substances in the conjunctiva. PGD2 was weakly pruritogenic but PGF2 alpha and the TxA2-mimetic U-46619 were inactive. The PG precursor arachidonic acid was also a potent pruritogen and its effects were inhibited by ketorolac pretreatment. Ketorolac also dose-dependently inhibited the itching associated with experimental allergic conjunctivitis. It appears that PGs are potent itch-producing substances in the conjunctiva and the anti-itch efficacy of ketorolac in allergic conjunctivitis appears to involve inhibition of conjunctival PG biosynthesis from arachidonic acid.
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PMID:The pruritogenic and inflammatory effects of prostanoids in the conjunctiva. 859 Feb 66

We previously reported that intrathecal administration of prostaglandin (PG) D2 and PGE2 to conscious mice induced hyperalgesia (assessed by a hot-plate test) and that intrathecal administration of PGE2 and PGF2 alpha induced allodynia, a state of discomfort and pain evoked by innocuous tactile stimuli. In the present study, we examined the relationships of pain responses among PGD2, PGE2 and PGF2 alpha, PGF2 alpha additively augmented the allodynia evoked by a submaximal dose (1 ng/mouse) of PGE2. On the other hand, PGD2 dose-dependently blocked the allodynia induced by a maximal dose (10 ng/mouse) of PGE2, with an IC50 of 93.2 pg/mouse, but did not affect the PGE2 (10 ng)-induced hyperalgesia at doses up to 10 ng. BW 245C, an agonist for PGD2 receptors (DP receptors), but not another DP receptor agonist (ZK 110841) blocked the allodynia similarly. The blockade of PGE2-induced allodynia by 10 ng of PGD2 was reversed by the potent and selective DP receptor antagonist BW A868C, in a dose-dependent manner. Intrathecal administration of BW A868C induced allodynia by itself over a wide range, from 10 pg to 100 ng. and the allodynia induced by 100 ng of BW A868C was dose-dependently antagonized by PGD2. These results demonstrate that PGD2 blocked the PGE2-evoked allodynia through DP receptors in the spinal cord, and they imply that endogenous PGD2 may play an inhibitory role in the appearance of allodynia under physiological conditions.
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PMID:Prostaglandin D2 inhibits prostaglandin E2-induced allodynia in conscious mice. 881 97

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

Idiopathic trigeminal neuralgia (ITN), resistant to the drug treatment was diagnosed in 20 patients using following parameters: clinical feature, usage of Bell-McGill questionnaire, as well as X-ray and neurophysiologic examinations. Peripheral neurectomy was performed in all of them as a palliative therapeutic procedure. In removed nerves of patients (n. infraorbitalis, n. alveolaris inferior), as well as in the same nerves of cadavers, the concentrations of prostaglandins (PGs) E2, F2 alpha and D2 were determined using commercial radioimmunoassay. Significant increase in PGE2 and PGF2 alpha concentration and simultaneous decrease in PGD2 concentration in the nerves of the patients with ITN was noticed. Results demonstrated that the increase in the concentration of hyperalgesic PGE2 and PGF2 alpha as well as the decrease in hypoalgesic PGD2 concentration had an important role in the onset of neuralgic pain in patients with ITN.
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PMID:Do prostaglandins E2, F2 alpha and D2 have a role in the development of idiopathic trigeminal neuralgia? 917 96

While sympathetic efferents and prostaglandins (PGs) play an important role in hyperalgesia of partial injury of peripheral nerves and inflammation, whether these are also involved in diabetic hyperalgesia is unknown. With intraperitoneal injection of 6-hydroxydopamine (6-OHDA) to eliminate effects of sympathetic postganglionic neurons (SPGNs) terminals, a model of diabetic rats with infused 6-OHDA could be set up by injection of streptozotocin (STZ). Nociceptive paw-withdrawal threshold (NPWT) and tail flick latency (TFL) in 6-OHDA/diabetic rats were not changed significantly in the following four weeks. However, in diabetic group rats, pain threshold was decreased significantly and accompanied by development of hyperalgesia. NPWT was significantly decreased with noradrenaline (NA) in diabetic hyperalgesic rats and increased with phentolamine or yohimbine, but not by prazocin. In the control rats, NPWT are not changed significantly by NA or phentolamine, and in 6-OHDA/diabetic rats, neither NA nor phentolamine also affected on NPWT significantly. However, NPWT may be significantly decreased by PGE1, PGE2 and PGD2 in both the control and the diabetic hyperalgesic rats. The above results suggested that SPGNs terminals are involved in hyperalgesia of diabetic rats, NA accelerated synthesis of PGs and released by way of presynaptic effect on alpha 2-adrenergic receptors at the SPGNs terminals, PGs, in turn, directly acted on the primary afferent nociceptors, producing hyperalgesia.
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PMID:[Effects of sympathetic efferent in diabetic hyperalgesia in rat]. 938 51

Prostaglandin (PG) D2 is the most abundant prostanoid produced in the central nervous system of mammals and has been implicated in the modulation of neural functions such as sleep induction, nociception, regulation of body temperature, and odor responses. We generated gene-knockout mice for lipocalin-type PGD2 synthase (L-PGDS) and found that the intrathecal administration of PGE2, an endogenous pain-producing substance, failed to elicit allodynia (touch-evoked pain), which is one typical phenomenon of neuropathic pain, whereas it evoked thermal hyperalgesia, in L-PGDS-/- mice. We also found that the allodynic response induced by the gamma-aminobutyric acid (GABA)A receptor antagonist bicuculline was selectively abolished in the L-PGDS-/- mice, among excitatory and inhibitory agents that induced allodynia in wild-type mice. Interestingly, simultaneous injection of a femtogram amount of PGD2 with PGE2 or bicuculline induced allodynia in L-PGDS-/- mice to the same extent as in wild-type mice. The PGE2- or bicuculline-evoked allodynia in wild-type and in PGD2-supplemented L-PGDS-/- mice was blocked by a PGD2 receptor antagonist given in a femtogram amount. These results reveal that endogenous PGD2 is essential for both PGE2- and bicuculline-induced allodynia.
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PMID:Lack of tactile pain (allodynia) in lipocalin-type prostaglandin D synthase-deficient mice. 989 1


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