dinoprost and Headache

Human models of headache may contribute to understanding of prostaglandins' role in migraine pathogenesis. The current thesis investigated the migraine triggering effect of prostaglandin E2 (PGE2) in migraine patients without aura, the efficacy of a novel EP4 receptor antagonist, BGC20-1531, in prevention of PGE2-induced headache and the ability of prostaglandin F2α (PGF2α) to trigger headache without any vasodilatation in healthy volunteers. All studies were designed as double-blind, placebo-controlled, cross-over experiments, where PGE2/PGF2α or saline were infused over 20-25 min. In the study with EP4 receptor antagonist healthy volunteers were pre-treated with two different doses of BGC20-1531 or placebo followed by PGE2 infusion over 25 min. The headache data were collected during the whole study day, whereas the possible vascular changes were measured during the in-hospital phase of 1.5 h. The infusion of PGE2 caused the immediate migraine-like attacks and vasodilatation of the middle cerebral artery in migraine patients without aura. The highly specific and potent EP4 receptor antagonist, BGC20-1531, was not able to attenuate PGE2-induced headache and vasodilatation of both intra- and extra-cerebral arteries. The intravenous infusion of PGF2α did not induce headache or statistically significant vasoconstriction of cerebral arteries in healthy volunteers. Novel data on PGE2-provoked immediate migraine-like attacks suggest that PGE2 may be one of the important final products in the pathogenesis of migraine. The lack of efficacy of EP4 receptor antagonist suggests that a single receptor blockade is not sufficient to block PGE2 responses, hence EP2 receptor should be investigated as a potential drug target for the treatment of migraine. The absence of headache during the PGF2α infusion demonstrates that vasodilating properties are necessary for the induction of headache and migraine.

Topics: Adolescent; Adult; Blood Flow Velocity; Blood Pressure; Dinoprost; Dinoprostone; Double-Blind Method; Headache; Heart Rate; Humans; Middle Aged; Middle Cerebral Artery; Migraine without Aura; Pyridines; Radial Artery; Receptors, Prostaglandin E, EP4 Subtype; Sulfonamides; Temporal Arteries; Time Factors; Ultrasonography; Vasodilation; Young Adult

To observe the clinical efficacy of acupuncture combined with auricular point sticking for menstrual headache and to discuss its mechanism.. Eighty-five patients with menstrual headache were randomly divided into an observation group (43 cases) and a control group (42 cases). The observation group was treated with body acupuncture combined with auricular point sticking and the control group was treated with flunarizine hydrochloride capsules orally. The treatments of 3 menstrual cycles were required. The clinical efficacy was observed in the two groups. The content of serum prostaglandin F2α, (PGF2α) and plasma arginine vasopressin (AVP) in the menstrual periods of some patients randomly selected in the two groups was tested before and after treatment and was compared with that of 20 cases in a normal group. Results The total effective rate was 95.4% (41/43) in the observation group which was obviously superior to 81.0% (34/42) in the control group (P<0.01). Before treatment, the content of serum PGF2α and plasma AVP of patients in the two groups was higher than that in the normal group (all P<0.01). After treatment,the content of serum PGF2α and plasma AVP was lower than that before treatment in the two groups (P<0.01, P<0.05). The content of serum PGF2α in the observation group was decreased significantly compared with that in the control group (P<0.05) and returned to the level of the normal group.. Body acupuncture combined with auricular point sticking achieves positive efficacy for menstrual headache and its mechanism could be related to regulating the abnormal levels of serum PGF2α and plasma AVP.

Topics: Acupuncture Therapy; Acupuncture, Ear; Adolescent; Adult; Arginine Vasopressin; Dinoprost; Female; Headache; Humans; Menstruation; Premenstrual Syndrome; Treatment Outcome; Young Adult

Clinical trials use placebos with the assumption that they are inert, thus all placebos are considered to be equal. Here we show that this assumption is wrong and that different placebo procedures are associated to different therapeutic rituals which, in turn, trigger different mechanisms and produce different therapeutic outcomes. We studied high altitude, or hypobaric hypoxia, headache, in which two different placebos were administered. The first was placebo oxygen inhaled through a mask, whereas the second was placebo aspirin swallowed with a pill. Both placebos were given after a conditioning procedure, whereby either real oxygen or real aspirin was administered for three consecutive sessions to reduce headache pain. We found that after real oxygen conditioning, placebo oxygen induced pain relief along with a reduction in ventilation, blood alkalosis and salivary prostaglandin (PG)E2, yet without any increase in blood oxygen saturation (SO2). By contrast, after real aspirin conditioning, placebo aspirin induced pain relief through the inhibition of all the products of cyclooxygenase, that is, PGD2, PGE2, PGF2, PGI2, thromboxane (TX)A2, without affecting ventilation and blood alkalosis. Therefore, two different placebos, associated to two different therapeutic rituals, used two different pathways to reduce headache pain. The analgesic effect following placebo oxygen was superior to placebo aspirin. These findings show that different placebos may use different mechanisms to reduce high altitude headache, depending on the therapeutic ritual and the route of administration. In clinical trials, placebos and outcome measures should be selected very carefully in order not to incur in wrong interpretations.

Topics: Adult; Dinoprost; Dinoprostone; Epoprostenol; Female; Headache; Humans; Hypoxia; Male; Oxygen; Prostaglandin D2; Thromboxane A2

Human models of headache may contribute to understanding of prostaglandins' role in migraine pathogenesis. The current thesis investigated the migraine triggering effect of prostaglandin E2 (PGE2) in migraine patients without aura, the efficacy of a novel EP4 receptor antagonist, BGC20-1531, in prevention of PGE2-induced headache and the ability of prostaglandin F2α (PGF2α) to trigger headache without any vasodilatation in healthy volunteers. All studies were designed as double-blind, placebo-controlled, cross-over experiments, where PGE2/PGF2α or saline were infused over 20-25 min. In the study with EP4 receptor antagonist healthy volunteers were pre-treated with two different doses of BGC20-1531 or placebo followed by PGE2 infusion over 25 min. The headache data were collected during the whole study day, whereas the possible vascular changes were measured during the in-hospital phase of 1.5 h. The infusion of PGE2 caused the immediate migraine-like attacks and vasodilatation of the middle cerebral artery in migraine patients without aura. The highly specific and potent EP4 receptor antagonist, BGC20-1531, was not able to attenuate PGE2-induced headache and vasodilatation of both intra- and extra-cerebral arteries. The intravenous infusion of PGF2α did not induce headache or statistically significant vasoconstriction of cerebral arteries in healthy volunteers. Novel data on PGE2-provoked immediate migraine-like attacks suggest that PGE2 may be one of the important final products in the pathogenesis of migraine. The lack of efficacy of EP4 receptor antagonist suggests that a single receptor blockade is not sufficient to block PGE2 responses, hence EP2 receptor should be investigated as a potential drug target for the treatment of migraine. The absence of headache during the PGF2α infusion demonstrates that vasodilating properties are necessary for the induction of headache and migraine.

Topics: Adolescent; Adult; Blood Flow Velocity; Blood Pressure; Dinoprost; Dinoprostone; Double-Blind Method; Headache; Heart Rate; Humans; Middle Aged; Middle Cerebral Artery; Migraine without Aura; Pyridines; Radial Artery; Receptors, Prostaglandin E, EP4 Subtype; Sulfonamides; Temporal Arteries; Time Factors; Ultrasonography; Vasodilation; Young Adult

During two decades of migraine provocation studies with naturally occurring signalling molecules, vasodilators such as prostaglandin E(2), prostaglandin I(2) (prostacyclin) and prostaglandin D(2) were shown to be able to induce headache in man. To elucidate the role of inflammation and vasodilatation in the generation of headache, we investigated whether the pro-inflammatory and vasoconstricting prostanoid prostaglandin F(2α) (PGF(2α)) would cause headache in a human model of headache.. Twelve healthy volunteers were randomly allocated to receive 3.5 µg/kg/min PGF(2α) or placebo over 20 min in a two-way crossover study. We recorded headache intensity on a verbal rating scale, middle cerebral artery blood flow velocity (V(MCA)) and the diameters of the superficial temporal artery (STA) and radial artery (RA).. We found no difference in the area under the curve (AUC) for immediate headache (0-90 min) between PGF(2α) and placebo (p = 0.144). The McNemar's test showed no difference in the incidence of immediate and delayed headache between verum and placebo (p = 0.500 and p = 1.000, respectively). There was no difference in V(MCA) (p = 0.776) and in the diameter of the STA (p = 0.460) or RA (p = 0.780) between PGF(2α) and placebo.. The present study shows that PGF(2α), unlike vasodilating prostaglandins, does not provoke headache. We suggest that the vasodilating abilities of prostaglandins are important for the induction of experimental headache in healthy volunteers.

Topics: Adult; Arteries; Cross-Over Studies; Dinoprost; Female; Headache; Humans; Inflammation Mediators; Male; Vasoconstrictor Agents; Young Adult

Hypotensive and other ocular effects were studied for 24 hr after topical application of prostaglandin F2 alpha as the tromethamine salt (PGF2 alpha) in 45 normotensive human subjects. After baseline intraocular pressure (IOP) measurements, 62.5 micrograms, 125 micrograms and 250 micrograms of PGF2 alpha dissolved in 50 microliter of saline was applied to one eye of 15 subjects for each dose tested. Contralateral control eyes received 50 microliter of saline. As compared with the IOP of the contralateral control eyes, topical application of 62.5 micrograms PGF2 alpha caused a significant IOP reduction at 1-12 hr, with a maximal IOP reduction of 2.2 mm Hg at 2 hr. Treatment with 125 micrograms of PGF2 alpha lowered IOP significantly at 1-21 hr, with a maximal reduction of 3.1 mm Hg at 9 hr. Administration of 250 micrograms PGF2 alpha produced a significant reduction of IOP, which lasted for at least 24 hr. A maximal IOP reduction of 2.9 mm Hg occurred at 7 hr. Pupillary diameter was not altered. Aqueous flare and anterior chamber cellular response were not seen in any of the eyes of the subjects at any time after topical application of 62.5-250 micrograms PGF2 alpha. The drug caused side effects consisting of reddened skin of lower lid, ocular irritation, conjunctival hyperemia and headache.

Topics: Administration, Topical; Adult; Dinoprost; Erythema; Eye; Female; Headache; Humans; Hyperemia; Intraocular Pressure; Male; Middle Aged; Reference Values; Time Factors

The ocular effects of 200 micrograms of topically applied prostaglandin F2 alpha were studied in 18 nonglaucomatous volunteers. A fall in intraocular pressure was seen in the prostaglandin-treated eyes when compared with the placebo-treated control eyes. The maximum intraocular pressure reduction was observed at the 7th h and hypotensive ocular effect persisted for 24 h. Prostaglandins did not produce any change in pupillary diameter or signs of intraocular inflammation visible by anterior segment biomicroscopy or iris fluorescein angiography. The drug caused side effects: conjunctival hyperemia was constant and many patients complained of ocular smarting and headache. It could be useful in the treatment of ocular hypertension, although its usefulness would be limited by the side effects.

Topics: Adult; Aged; Conjunctiva; Dinoprost; Eye; Female; Headache; Humans; Hyperemia; Intraocular Pressure; Male; Middle Aged; Prostaglandins F

The Authors valued effects of the extinction-test with Thiapride (200 mg i.v.) in the primary headaches. They particularly noticed a significant reduction of PGF2-alpha and PRL, together with an increase of 5-HT and beta-ELI in CSF.

Topics: Adult; Benzamides; beta-Endorphin; Dinoprost; Endorphins; Headache; Humans; Middle Aged; Prolactin; Prostaglandins F; Serotonin; Tiapamil Hydrochloride

The authors described the results about the action of indoprofen (i.v. 400 mg) in three subjects affected by premenstrual migraine. They showed decreased levels of PGF2 alpha in the cerebrospinal fluid evaluated by gas-chromatography and mass spectrometry. The samples were extracted at 0, 15, 30 and 45 minutes. The levels of pain, was also decreased, they were evaluated by the analogic visual scale (V.A.S.).

Topics: Adult; Dinoprost; Female; Gas Chromatography-Mass Spectrometry; Headache; Humans; Indoprofen; Phenylpropionates; Premenstrual Syndrome; Prostaglandins F