Vasoactive Intestinal Peptide Causes Marked Cephalic Vasodilation, but does not Induce Migraine

Cephalalgia ◽  
2008 ◽  
Vol 28 (3) ◽  
pp. 226-236 ◽  
Author(s):  
A Rahmann ◽  
T Wienecke ◽  
JM Hansen ◽  
J Fahrenkrug ◽  
J Olesen ◽  
...  
Keyword(s):  
Vasoactive Intestinal Peptide ◽  
Rating Scale ◽  
Superficial Temporal Artery ◽  
Temporal Artery ◽  
High Frequency Ultrasound ◽  
Double Blind ◽  
Vascular Origin ◽  
Cranial Arteries ◽  
To Receive ◽  
Double Blind Crossover Study

We hypothesized that intravenous infusion of the parasympathetic transmitter, vasoactive intestinal peptide (VIP), might induce migraine attacks in migraineurs. Twelve patients with migraine without aura were allocated to receive 8 pmol kg-1 min-1 VIP or placebo in a randomized, double-blind crossover study. Headache was scored on a verbal rating scale (VRS), mean blood flow velocity in the middle cerebral artery ( Vmean mca) was measured by transcranial Doppler ultrasonography, and diameter of the superficial temporal artery (STA) by high-frequency ultrasound. None of the subjects reported a migraine attack after VIP infusion. VIP induced a mild immediate headache (maximum 2 on VRS) compared with placebo ( P = 0.005). Three patients reported delayed headache (3-11 h after infusion) after VIP and two after placebo ( P = 0.89). Vmean mca decreased (16.3 ± 5.9%) and diameter of STA increased significantly after VIP (45.9 ± 13.9%). VIP mediates a marked dilation of cranial arteries, but does not trigger migraine attacks in migraineurs. These data provide further evidence against a purely vascular origin of migraine.

The Cholinomimetic Agent Carbachol Induces Headache in Healthy Subjects

Cephalalgia ◽  
2009 ◽  
Vol 29 (2) ◽  
pp. 258-268 ◽  
Author(s):  
HW Schytz ◽  
T Wieneckey ◽  
PS Oturai ◽  
J Olesen ◽  
M Ashina
Keyword(s):  
Healthy Subjects ◽  
Rating Scale ◽  
Parasympathetic Nervous System ◽  
Superficial Temporal Artery ◽  
Area Under The Curve ◽  
Temporal Artery ◽  
Double Blind ◽  
Migraine Pathogenesis ◽  
Blind Crossover Study ◽  
Double Blind Crossover Study

The parasympathetic nervous system is likely to be involved in migraine pathogenesis. We hypothesized that the cholinomimetic agonist carbachol would induce headache and vasodilation of cephalic and radial arteries. Carbachol (3 μg/kg) or placebo was randomly infused into 12 healthy subjects in a double-blind crossover study. Headache was scored on a verbal rating scale from 0–10. Velocity in the middle cerebral artery (Vmca) and diameter of the superficial temporal artery (STA) and radial artery (RA) were recorded. Nine participants developed headache after carbachol compared with three after placebo. The area under the curve for headache was increased after carbachol compared with placebo both during infusion (0–30 min) ( P = 0.042) and in the postinfusion period (30–90 min) ( P = 0.027). Carbachol infusion caused a drop in Vmca ( P = 0.003) and an increase in STA diameter ( P = 0.006), but no increase in the RA diameter ( P = 0.200). In conclusion, the study demonstrated that carbachol caused headache and dilation of cephalic arteries in healthy subjects.

Carbachol induces headache, but not migraine-like attacks, in patients with migraine without aura

Cephalalgia ◽  
2009 ◽  
Vol 30 (3) ◽  
pp. 337-345 ◽  
Author(s):  
HW Schytz ◽  
T Wienecke ◽  
J Olesen ◽  
M Ashina
Keyword(s):  
Crossover Study ◽  
Middle Cerebral Artery ◽  
Healthy Subjects ◽  
Migraine Without Aura ◽  
Rating Scale ◽  
Superficial Temporal Artery ◽  
Temporal Artery ◽  
Double Blind ◽  
Blind Crossover Study ◽  
Double Blind Crossover Study

Carbachol induces headache in healthy subjects, but the migraine eliciting effect of carbachol has not previously been studied. We hypothesized that the cholinomimetic agonist carbachol would induce headache and migraine-like attacks in migraineurs. Carbachol (3 µg/kg) or placebo was randomly infused into 18 patients with migraine without aura in a double-blind crossover study. Headache was scored on a verbal rating scale from 0 to 10. Velocity in the middle cerebral artery (VMCA) and diameter of the superficial temporal artery (STA) were recorded. Fifteen patients experienced headache after carbachol compared with eight after placebo ( P = 0.039). There was no difference in incidence of migraine-like attacks after carbachol ( n = 8) compared with placebo ( n = 6) ( P = 0.687). Carbachol caused a decrease in VMCA ( P = 0.044), but no change in STA ( P = 0.089) compared with placebo. The study demonstrated that carbachol provocation is not a good model for experimental migraine.

Prostaglandin E2 (PGE2) Induces Headache in Healthy Subjects

Cephalalgia ◽  
2009 ◽  
Vol 29 (5) ◽  
pp. 509-519 ◽  
Author(s):  
T Wienecke ◽  
J Olesen ◽  
PS Oturai ◽  
M Ashina
Keyword(s):  
Healthy Subjects ◽  
Rating Scale ◽  
Superficial Temporal Artery ◽  
Area Under The Curve ◽  
Temporal Artery ◽  
Prostaglandin E ◽  
Double Blind Study ◽  
Mean Flow ◽  
Sensory Afferents ◽  
Double Blind

The role of prostanoids in nociception is well established. The headache-eliciting effects of prostaglandin E2 (PGE2) and its possible mechanisms have previously not been systematically studied in man. We hypothesized that infusion of PGE2 might induce headache and vasodilation of cranial vessels. PGE2 (0.40 μg kg−1 min−1) or saline was infused for 25 min into 11 healthy subjects in a cross-over, double-blind study. Headache intensity was scored on a verbal rating scale from 0 to 10. In addition, we recorded mean flow in the middle cerebral artery (VMCA) by transcranial Doppler and diameter of the superficial temporal artery (STA) by high-resolution ultrasonography. All 11 subjects reported headache on the PGE2 day and no subjects reported headache on the placebo day ( P = 0.001). During the immediate phase (0–30 min) ( P = 0.005) and the postinfusion phase (30–90 min) ( P = 0.005), the area under the curve for headache score was significantly larger on the PGE2 day compared with the placebo day. PGE2 caused dilatation of the STA (23.5%; 95% CI 14.0, 37.8) and the MCA (8.3%; 95% CI 4.0, 12.6). We suggest that PGE2 induces headache by activation and sensitization of cranial perivascular sensory afferents.

Discrepancy between strong cephalic arterial dilatation and mild headache caused by prostaglandin D2 (PGD2)

Cephalalgia ◽  
2010 ◽  
Vol 31 (1) ◽  
pp. 65-76 ◽  
Author(s):  
Troels Wienecke ◽  
Jes Olesen ◽  
Messoud Ashina
Keyword(s):  
Mast Cell ◽  
Superficial Temporal Artery ◽  
Temporal Artery ◽  
Mast Cell Degranulation ◽  
Prostaglandin D2 ◽  
Double Blind ◽  
Phase 0 ◽  
To Receive ◽  
Peak Increase ◽  
Mild Headache

Introduction: Prostaglandins (PGs) are involved in nociception and mast cell degranulation. Prostaglandin D2 (PGD2) is a vasodilatator released during mast cell degranulation. The headache-eliciting effect of PGD2 has not been studied in man. Subjects and methods: Twelve healthy volunteers were randomly allocated to receive intravenous infusion of 384 ng/kg/min PGD2 over 25 min in a placebo-controlled, double-blind cross-over study. We recorded headache intensity and associated symptoms, velocity in the middle cerebral artery (VMCA) and diameter of the superficial temporal artery (STA) and radial artery (RA) using ultrasonography. Results: In the period 0–14 h, 11 subjects reported headache on PGD2 compared to one subject on placebo ( P = 0.002). During the in-hospital phase (0–120 min), the area under the headache curve was larger on PGD2 compared to placebo ( P < 0.05). Median peak headache, 1 (0–1), occurred 10 min after start of PGD2 infusion. There was no difference in incidence of headache in the post-hospital phase between PGD2 ( n = 3) and placebo ( n = 1). There was a decrease in VMCA ( P < 0.001), increase in STA ( P < 0.001) and RA ( P < 0.006) diameter during PGD2 infusion compared to placebo. Peak decrease in VMCA was 28.3% after 10 min and peak increase in STA was 55.7% after 20 min on the PGD2 day. Conclusions: The present study shows that PGD2 is a very strong vasodilator of MCA, STA and RA, but causes only mild headache.

Pro-inflammatory and vasoconstricting prostanoid PGF2α causes no headache in man

Cephalalgia ◽  
2011 ◽  
Vol 31 (15) ◽  
pp. 1532-1541 ◽  
Author(s):  
Maria Antonova ◽  
Troels Wienecke ◽  
Jes Olesen ◽  
Messoud Ashina
Keyword(s):  
Healthy Volunteers ◽  
Rating Scale ◽  
Superficial Temporal Artery ◽  
Area Under The Curve ◽  
Temporal Artery ◽  
Human Model ◽  
Prostaglandin E ◽  
Signalling Molecules ◽  
Prostaglandin F

Background: During two decades of migraine provocation studies with naturally occurring signalling molecules, vasodilators such as prostaglandin E2, prostaglandin I2 (prostacyclin) and prostaglandin D2 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 F2α (PGF2α) would cause headache in a human model of headache. Methods: Twelve healthy volunteers were randomly allocated to receive 3.5 µg/kg/min PGF2α 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 (VMCA) and the diameters of the superficial temporal artery (STA) and radial artery (RA). Results: We found no difference in the area under the curve (AUC) for immediate headache (0–90 min) between PGF2α 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 VMCA ( p = 0.776) and in the diameter of the STA ( p = 0.460) or RA ( p = 0.780) between PGF2α and placebo. Conclusion: The present study shows that PGF2α, 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.

The Efficacy of Electroconvulsive Therapy in the Treatment of Schizophrenia

1987 ◽  
Vol 151 (2) ◽  
pp. 152-155 ◽  
Author(s):  
K. R. Abraham ◽  
P. Kulhara
Keyword(s):  
Electroconvulsive Therapy ◽  
Rating Scale ◽  
Double Blind Trial ◽  
Double Blind ◽  
Blind Trial ◽  
Brief Psychiatric Rating Scale ◽  
Psychiatric Rating ◽  
Psychiatric Rating Scale ◽  
To Receive

The efficacy of ECT was investigated in a double-blind trial. Twenty-two patients with schizophrenia received trifluoperazine and were randomly allocated to receive eight real or eight simulated ECTs. In the first eight weeks, the group receiving real ECTs showed significantly more improvement as measured on the Brief Psychiatric Rating Scale. However, the groups showed no significant differences from the twelfth week onwards. The superiority of real ECT was not confirmed at the end of six months.

The Effect of Propranolol on Glyceryltrinitrate-Induced Headache and Arterial Response

Cephalalgia ◽  
2004 ◽  
Vol 24 (12) ◽  
pp. 1076-1087 ◽  
Author(s):  
JF Tvedskov ◽  
LL Thomsen ◽  
LL Thomsen ◽  
HK Iversen ◽  
P Williams ◽  
...  
Keyword(s):  
Healthy Subjects ◽  
Migraine Without Aura ◽  
Rating Scale ◽  
No Reduction ◽  
International Headache Society ◽  
Cerebral Arteries ◽  
Superficial Temporal Artery ◽  
New Drugs ◽  
Prophylactic Effect ◽  
Double Blind

Prophylactic drug trials in migraine are long-lasting and expensive and require long-term toxicology information. A human migraine model would therefore be helpful in testing new drugs. Immediate headache and delayed migraine after glyceryltrinitrate (GTN) has been well characterized. We have recently shown that sodium valproate has prophylactic effect in the GTN model. Here we report our experience with propranolol in this model. Nineteen subjects with migraine without aura and 16 sex- and aged-matched healthy subjects were included in a two-centre randomized double-blind cross-over study. Fourteen migraine subjects and 14 healthy subjects completed the study and results from comparison of the 28 subjects are reported. Randomly propranolol 160 mg or placebo were each given daily for 14 days to both migraine and healthy subjects. A 20-min intravenous infusion of GTN 0.25 mg/kg per min was administered on a study day at the end of both pretreatment periods. Headache was registered for 12 h after GTN infusions. Its intensity was scored on a numerical verbal rating scale from 0 to 10. Fulfilment of International Headache Society (HIS) criteria was recorded for 24 h. Radial and superficial temporal artery diameters and blood velocity of both middle cerebral arteries were measured. All migraine subjects developed headache after GTN. No reduction of overall peak headache was found after propranolol (median 5, range 0-7) compared with placebo (median 5, range 0-10) ( P = 0.441). Eight of the 14 completing migraine subject developed IHS 1.1 migraine after GTN, two subjects on both days, three subjects only after placebo, and three subjects only after propranolol. No reduction of GTN-induced migraine was found after propranolol compared with placebo (5 vs. 5, P = 1.000). All healthy subjects developed headache after GTN. No reduction of overall peak headache was found after propranolol (median 2, range 1-5) compared with placebo (median 1, range 1-7) ( P = 0.315). Two subjects fulfilled IHS criteria 1.1 for migraine without aura after propranolol but not after placebo. The fulfilment was short lasting and did not require rescue medication. Headache after GTN was more pronounced in migraine subjects than in healthy subjects both with ( P = 0.003) and without pretreatment with propranolol ( P = 0.017). We found that 2 weeks of propranolol constricted the radial artery in healthy subjects but not in migraine subjects. GTN-induced vasodilatation abolished this difference. Mean maximum blood flow velocity in the middle cerebral artery was higher in healthy subjects than in migraine patients ( P = 0.003-0.033) and unaffected by propranolol. We observed no effect of propranolol on GTN-induced headache and migraine. This could indicate that GTN induces migraine at a deeper level of the pathophysiological cascade of migraine than the prophylactic effect of propranolol. Propranolol does not constrict cerebral arteries, which therefore cannot be part of its mechanism of action in migraine.

A randomized double-blind comparison of ondansetron and metoclopramide in the prophylaxis of emesis induced by cyclophosphamide, fluorouracil, and doxorubicin or epirubicin chemotherapy.

1990 ◽  
Vol 8 (6) ◽  
pp. 1063-1069 ◽  
Author(s):  
J Bonneterre ◽  
B Chevallier ◽  
R Metz ◽  
P Fargeot ◽  
E Pujade-Lauraine ◽  
...  
Keyword(s):  
Group Analysis ◽  
Loading Dose ◽  
Breast Cancer Patients ◽  
Double Blind ◽  
Parallel Group ◽  
Blind Comparison ◽  
Prophylaxis Of Emesis ◽  
To Receive ◽  
Blind Crossover Study ◽  
Double Blind Crossover Study

Seventy-five breast cancer patients scheduled to receive a first course (in a new cycle) of cyclophosphamide, fluorouracil, and doxorubicin (FAC) or epirubicin (FEC) participated in a double-blind crossover study to compare the antiemetic efficacy and safety of ondansetron (GR38032), a 5-hydroxytryptamine3 (5-HT3) receptor antagonist, and metoclopramide. Ondansetron was given as an 8 mg loading dose (4 mg intravenously [IV] plus 4 mg orally) before chemotherapy followed by 8 mg every 8 hours orally for 3 to 5 days. Metoclopramide was given as an 80 mg loading dose (60 mg IV plus 20 mg orally) before chemotherapy followed by 20 mg every 8 hours orally for 3 to 5 days. A "period" interaction in the analysis of emetic response in the first 24 hours necessitated a parallel group analysis of first treatments only, 68 patients being assessable for this parameter. In the first 24 hours, complete or major control (zero to two emetic episodes) of emesis was achieved in 30 of 35 (86%) patients receiving ondansetron and in 14 of 33 (42%) patients receiving metoclopramide (P less than .001). Ondansetron was also more effective in reducing acute nausea. On days 2 to 3, the complete or major responses were significantly better with ondansetron (81% v 65%; P = .033), but there was no statistical difference in the control of nausea. There was a significant patient preference for ondansetron (63% v 26%; P = .001). Extrapyramidal reactions were observed in two metoclopramide treatments; both treatments were otherwise well tolerated. These results are consistent with serotonin (5-HT), being a significant neurotransmitter of cyclophosphamide/doxorubicin- or epirubicin/fluorouracil-induced emesis.

scholarly journals Sexual Function during Bupropion or Paroxetine Treatment of Major Depressive Disorder

2006 ◽  
Vol 51 (4) ◽  
pp. 234-242 ◽  
Author(s):  
Sidney H Kennedy ◽  
Kari A Fulton ◽  
R Michael Bagby ◽  
Andrea L Greene ◽  
Nicole L Cohen ◽  
...  
Keyword(s):  
Major Depressive Disorder ◽  
Depressive Disorder ◽  
Sexual Function ◽  
Rating Scale ◽  
Primary Objective ◽  
Major Depressive ◽  
Double Blind ◽  
Significant Difference ◽  
To Receive ◽  
Over Time

Objective: The primary objective was to evaluate sexual function (SF) separately in men and women with major depressive disorder (MDD) before and during treatment with bupropion sustained release (SR) or paroxetine. The secondary objectives involved a comparative evaluation of the Sex Effects Scale (Sex FX) and the Investigator-Rated Sexual Desire and Functioning Scale (IRSD-F), as well as a comparison of antidepressant outcomes and an examination of the relation between level of depression and SF over time. Method: There were 141 patients (68 women and 73 men) who met DSM-IV criteria for a current major depressive episode. They were randomly assigned to receive bupropion SR (150 to 300 mg daily) or paroxetine (20 to 40 mg daily) under double-blind trial conditions. Patients were assessed at baseline and at 2, 4, 6, and 8 weeks with the 17-item Hamilton Depression Rating Scale (HDRS17), Sex FX, and IRSD-F. Results: Prior to treatment, women reported significantly lower SF on both the Sex FX and IRSD-F scales, compared with men. During treatment, there were no significant drug differences on measures of SF over time for women; however, men who were treated with paroxetine reported a worsening of SF, whereas bupropion SR did not significantly alter SF. Both bupropion SR and paroxetine produced clinically and statistically significant reductions in HDRS17 scores as well as comparable rates of response and remission. There was a statistically significant correlation between the 2 measures of SF at all visits. There was also a significant inverse relation between depression and SF in women, but not in men, irrespective of drug. Conclusion: According to the Sex FX scale, a significant difference in antidepressant-related sexual dysfunction was detected in men, but not women, during treatment with bupropion SR or paroxetine.

Two-hour infusion of vasoactive intestinal polypeptide induces delayed headache and extracranial vasodilation in healthy volunteers

Cephalalgia ◽  
2020 ◽  
Vol 40 (11) ◽  
pp. 1212-1223 ◽  
Author(s):  
Lanfranco Pellesi ◽  
Mohammad Al-Mahdi Al-Karagholi ◽  
Basit Ali Chaudhry ◽  
Cristina Lopez Lopez ◽  
Josefin Snellman ◽  
...  
Keyword(s):  
Healthy Volunteers ◽  
Intravenous Infusion ◽  
Superficial Temporal Artery ◽  
Area Under The Curve ◽  
Temporal Artery ◽  
Continuous Intravenous Infusion ◽  
Headache Intensity ◽  
Parasympathetic System ◽  
The Difference ◽  
Cranial Arteries

Background In recent years, vasoactive intestinal peptide (VIP) and pituitary adenylate cyclase-activating polypeptides (PACAPs) have gained special interest in headache science. VIP and PACAPs (two isoforms, PACAP27 and PACAP38) are related in structure and function, as are their receptors, but they show differences in vasodilating- and headache-inducing properties. Intravenous infusion of PACAP27 or PACAP38, but not VIP, induces a long-lasting dilation of cranial arteries and delayed headache. The relationship between the long-lasting cranial vasodilation and headache development is not fully clarified. Methods In a double-blinded, placebo-controlled, crossover study in 12 healthy volunteers, diameter changes of cranial arteries, occurrence of headache and the parasympathetic system were examined before, during and after a 2-hour continuous intravenous infusion of VIP and placebo. Primary endpoints were the differences in area under the curve for the superficial temporal artery diameter and headache intensity scores, as well as in headache incidence, between VIP and placebo. Results The superficial temporal artery diameter was significantly larger on the VIP day compared to placebo ( p < 0.001) and the dilation lasted for more than 2 h. The incidence of headache was higher ( p = 0.003) on the VIP day compared to the placebo day. The difference in headache intensity scores was more evident in the post-infusion period (120–200 min, p = 0.034) and in the post-hospital phase (4–12 h, p = 0.025). Cranial parasympathetic activity, measured through the production of tears, was higher during VIP compared to placebo ( p = 0.033). Conclusion Continuous intravenous infusion of VIP over 2 h induced a long-lasting cranial vasodilation, activation of the cranial parasympathetic system, and delayed mild headaches in healthy volunteers. Trial Registration: The study is registered at ClinicalTrials.gov (NCT03989817).

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