Lack of correlation between vasodilatation and pharmacologically induced immediate headache in healthy subjects

Cephalalgia ◽  
2011 ◽  
Vol 31 (6) ◽  
pp. 683-690 ◽  
Author(s):  
Messoud Ashina ◽  
Peer Tfelt-Hansen ◽  
Peter Dalgaard ◽  
Jes Olesen
Keyword(s):  
Healthy Subjects ◽  
Rating Scale ◽  
Superficial Temporal Artery ◽  
Experimental Studies ◽  
Temporal Artery ◽  
Arterial Diameter ◽  
Mean Velocity ◽  
Headache Intensity ◽  
Scatter Plots ◽  
The Mean

Background: The causal relationship between experimental headache and vasodilatation has not been fully clarified. In the present study, we combined headache and vascular data from eight experimental studies and conducted detailed statistical analyses. Given that substances used in all these experiments were vasodilators we examined a possible correlation between headache scores and increases in arterial diameter. Methods: We identified nine studies and retrieved raw data in 89 healthy subjects (46 females, 43 males), mean age 27 years (range 18–59 years). The following variables were collected: maximal median headache intensity scores on a verbal rating scale (VRS) during immediate headache (0–120 minutes); the mean velocity of blood flow in the middle cerebral artery (VmeanMCA); and the diameter of the frontal branch of the superficial temporal artery (STA) during the maximal median headache intensity. Results: The scatter plots show no relationship between maximal headache score and the relative changes in VmeanMCA and diameter of the STA. The main analyses of covariance showed a significant effect only of heart rate on headache ( p = .014). The interaction tests were insignificant for all variables. Conclusions: The major outcome is a finding of no linear relationship between experimental immediate headache and dilatation of the MCA or STA.

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.

The effect of sodium nitroprusside on cerebral hemodynamics and headache in healthy subjects

Cephalalgia ◽  
2013 ◽  
Vol 33 (5) ◽  
pp. 301-307 ◽  
Author(s):  
Song Guo ◽  
Messoud Ashina ◽  
Jes Olesen ◽  
Steffen Birk
Keyword(s):  
Nitric Oxide ◽  
Sodium Nitroprusside ◽  
Healthy Subjects ◽  
Rating Scale ◽  
Cerebral Arteries ◽  
Superficial Temporal Artery ◽  
Temporal Artery ◽  
Dose Titration ◽  
End Tidal Carbon Dioxide ◽  
End Tidal

Investigation Sodium nitroprusside (SNP) is a powerful vasodilatory agent that, similarly to glyceryl trinitrate (GTN), releases nitric oxide (NO) but in contrast does not pass the blood-brain barrier. Nevertheless, it has already been used in animal models without any knowledge of its headache-inducing potential. We hypothesized that SNP would induce headache and vasodilation of cephalic and radial but not cerebral arteries. Methods Five healthy volunteers received intravenous infusions of SNP in a non-randomized dose-titration (1–5 µg/kg/min) study. We recorded headache intensity (verbal rating scale from 0 to 10), velocity in the middle cerebral artery (VMCA), and diameters of the superficial temporal artery (STA) and radial artery (RA). Results All participants reported a dose-related headache (median peak = 2.5, range 0–3). SNP dilated the STA and RA, caused a marked increase of heart rate and a decrease of mean arterial pressure (MAP) and partial pressure of end-tidal carbon dioxide (PetCO2). We found that SNP decreased the velocity of the VMCA, but this was canceled by a decrease of cerebral blood flow (CBF) due to hypocapnia. Conclusion The present study shows that SNP is a headache-inducing agent with close similarities to headaches induced by GTN and probably without effect on intracerebral arteries.

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.

Vasoactive Intestinal Polypeptide Evokes Only a Minimal Headache in Healthy Volunteers

Cephalalgia ◽  
2006 ◽  
Vol 26 (8) ◽  
pp. 992-1003 ◽  
Author(s):  
JM Hansen ◽  
J Sitarz ◽  
S Birk ◽  
AM Rahmann ◽  
PS Oturai ◽  
...  
Keyword(s):  
Vasoactive Intestinal Polypeptide ◽  
Healthy Subjects ◽  
Rating Scale ◽  
Superficial Temporal Artery ◽  
Photon Emission ◽  
Emission Computed Tomography ◽  
Mean Flow ◽  
Arterial Blood ◽  
Significant Difference ◽  
Intestinal Polypeptide

The role of the parasympathetic nervous system in the pathogenesis of migraine is disputed. The headache-eliciting effect of the parasympathetic neurotransmitter, vasoactive intestinal polypeptide (VIP), and its effect on cerebral arteries and brain haemodynamics has not been systematically studied in man. We hypothesized that infusion of VIP might induce headache in healthy subjects and cause changes in cerebral haemodynamics. VIP (8 pmol/kg per min) or placebo (0.9± saline) was infused for 25 min into 12 healthy young volunteers in a crossover, double-blind design. Headache was scored on a verbal rating scale from 0 to 10, regional cerebral blood flow (rCBF) was measured with single-photon emission computed tomography and 133Xe inhalation and mean flow velocity in the middle cerebral artery (VmeanMCA) was measured with transcranial Doppler ultrasonography. The headache was very mild with a maximum score of 2 and described as a pressing or throbbing sensation. Five participants developed headache during VIP and one during placebo. During the infusion, a significant drop in VmeanMCA was seen for VIP compared with placebo ( P < 0.001), but the effect quickly waned and no difference was found when comparing the time between 30 and 120 min. In addition, no significant difference in the diameter of the MCA could be found during the infusion. No significant differences in rCBF ( P = 0.10) were found between VIP and placebo. A marked dilation of the superficial temporal artery was seen ( P = 0.04) after VIP in the first 30 min but no difference was found when comparing the time between 30 and 120 min. We found no difference in mean arterial blood pressure between VIP and placebo days but the heart rate increased significantly on a VIP day compared with a placebo day (AUC0–30min, P < 0.001). Plasma VIP was significantly higher on a VIP day compared with placebo (AUC0–80min, P < 0.001). These results show that VIP causes a decrease in VmeanMCA without affecting rCBF. In spite of a marked vasodilator effect in the extracranial vessels and increased plasma VIP, healthy subjects developed only a very mild headache.

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.

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).

Radial Artery Graft for Bypass of the Maxillary to Proximal Middle Cerebral Artery: An Anatomic and Technical Study

Neurosurgery ◽  
2004 ◽  
Vol 54 (3) ◽  
pp. 667-671 ◽  
Author(s):  
Mehmet Erkan Üstün ◽  
Mustafa Büyükmumcu ◽  
Cagatay Han Ulku ◽  
Aynur Emine Cicekcibasi ◽  
Hamdi Arbag
Keyword(s):  
Middle Cerebral Artery ◽  
Radial Artery ◽  
Cerebral Artery ◽  
Superficial Temporal Artery ◽  
Temporal Artery ◽  
Radial Artery Graft ◽  
Artery Graft ◽  
Proximal Middle Cerebral Artery ◽  
The Mean ◽  
Artery Branch

Abstract OBJECTIVE In this study, we aimed to investigate the use of a radial artery graft for bypass of the maxillary artery (MA) to the proximal middle cerebral artery (MCA) as an alternative to superficial temporal artery-to-MCA anastomosis or extracranial carotid-to-MCA bypass using long grafts. METHODS Five adult cadavers were used bilaterally. After a frontotemporal craniotomy and a zygomatic arch osteotomy, the MA was found easily 1 to 2 cm inferior to the infratemporal crest. A hole was created with a 4-mm-tip drill in the sphenoid bone 2 to 3 mm lateral to the foramen rotundum extradurally, and the dura over the hole was opened. After the carotid and sylvian cisterns had been opened, the M2 segment of the MCA was exposed. The graft was passed through the hole to reach the M2 segment. Then, the MA was freed from the surrounding tissue and was transected before the infraorbital artery branch. The radial artery graft was anastomosed end-to-end to the MA proximally and end-to-side to the M2 segment of the MCA distally. RESULTS The mean thickness of the MA before the infraorbital artery branch was 2.6 ± 0.3 mm. The mean thickness of the largest trunk of the MCA was 2.3 ± 0.3 mm. The average length of the graft was 36 ± 5.5 mm. CONCLUSION MA-to-MCA bypass is as feasible as proximal MCA revascularization using long vein grafts. The thickness of the MA provides sufficient flow; the length of the graft is short, and it has a straight course. MA-to-proximal MCA bypass may be an alternative to superficial temporal artery-to-MCA as well as extracranial carotid-to-MCA bypasses.

Extracranial-Intracranial Bypass and Vessel Occlusion for the Treatment of Unclippable Giant Middle Cerebral Artery Aneurysms

Neurosurgery ◽  
2012 ◽  
Vol 72 (3) ◽  
pp. 428-436 ◽  
Author(s):  
M. Yashar S. Kalani ◽  
Joseph M. Zabramski ◽  
Yin C. Hu ◽  
Robert F. Spetzler
Keyword(s):  
Middle Cerebral Artery ◽  
Cerebral Artery ◽  
Saphenous Vein Graft ◽  
Superficial Temporal Artery ◽  
Temporal Artery ◽  
Parent Vessel ◽  
Vessel Occlusion ◽  
Bypass Patency ◽  
The Mean

Abstract BACKGROUND: Giant middle cerebral artery (MCA) aneurysms pose management challenges. OBJECTIVE: To review the outcomes of patients with giant MCA aneurysms not amenable to clipping or vessel reconstruction treated with extracranial-intracranial (EC-IC) bypass and vessel sacrifice. METHODS: We retrospectively reviewed a database of aneurysms treated at our institution between 1983 and 2011. RESULTS: Sixteen patients (11 males, 5 females) were identified. There were 10 saccular, 4 fusiform, and 2 serpentine aneurysms. The aneurysms predominantly involved the M1 segment in 5 cases, M2 in 9 cases, and both M1 and M2 in 2 cases. The EC-IC bypasses performed included 13 superficial temporal artery-MCA, 1 saphenous vein graft-MCA, and 2 radial artery grafts-MCA. The postoperative bypass patency rate was 93.8% (15/16). There were 3 cerebrovascular accidents (18.8%), but no perioperative deaths (0% mortality). The mean follow-up was 58.4 months (range, 1-265; median, 23.5 months). In 75% (12/16) of cases the aneurysms were occluded successfully. A small residual was noted in 3 cases with the use of this treatment strategy, and they were re-treated. In a fourth case treated with partial distal occlusion, reduced flow through the aneurysm was noted postoperatively, but the patient did not undergo further treatment. The mean modified Rankin scale and mean Glasgow Outcome Scale scores at last follow-up were 1.6 (range, 1-4; median, 1) and 4.8 (range, 3-5; median, 5), respectively. CONCLUSION: Giant MCA aneurysms are challenging lesions. EC-IC bypass with parent vessel occlusion can provide a durable form of treatment with acceptable rates of morbidity and mortality.

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