The role of nitric oxide in vascular headache.

Shortly after the invention of nitroglycerin (NTG), it was noticed that this substance is capable of inducing a violent headache. Only recently, it became known that this was due to the release of nitric oxide (NO) by NTG. As the molecular mechanism of migraine pain remains to be determined, NTG, being pro-drug for NO, has been used to study the aetiology and pathophysiology of migraine. Such studies with NTG- and also histamine-induced headaches, have led to propose that NO may be the causative molecule in migraine pain. The evidence supporting the role of NO in migraine is discussed, e.g. substances capable of inducing experimental vascular headache do so with NO as the common mediator, while drugs with antimigraine activity inhibit NO and the cascade of intracellular reactions triggered by NO. The importance of NO as a potential initiator of the migraine attack opens new directions for the pharmacological treatment of migraine and other vascular headaches.

CGRP may play a causative role in migraine.

Calcitonin gene-related peptide (CGRP) has been detected in increased amounts in external jugular venous blood during migraine attacks. However, it is unknown whether this is secondary to migraine or whether CGRP may cause headache. In a double-blind crossover study, the effect of human alphaCGRP (2 microg/min) or placebo infused intravenously for 20 min was studied in 12 patients suffering from migraine without aura. Headache intensity was scored on a scale from 0 to 10. Two patients were excluded due to severe hypotension and one because she had an infection. In the first hour median peak headache score was 1.0 in the halphaCGRP group vs. 0 in the placebo group (P < 0.01). During the following 11 h all patients experienced headaches after halphaCGRP vs. one patient after placebo (P = 0.0004). The median maximal headache score was 4 after CGRP and 0 after placebo (P = 0.006). In three patients after halphaCGRP, but in no patients after placebo, the delayed headache fulfilled the IHS criteria for migraine without aura. As intravenous administration of halphaCGRP causes headache and migraine in migraineurs, our study suggests that the increase in CGRP observed during spontaneous migraine attacks may play a causative role.

Effect of propylene glycol 1,2-dinitrate on cerebral blood flow in rats: a potential biomarker for vascular headache?

Two measurable indices of toxicity that can be correlated with exposure to propylene glycol dinitrate (PGDN) were evaluated along with its metabolism. Propylene glycol dinitrate was administered by rapid i.v. injection to male Fischer-344 rats. These rats demonstrated a dose-response of blood pressure (BP) to doses of PGDN ranging from 0.1 to 30 mg/kg; the maximum fall in systolic BP occurred within 1 min of dosing. The i.v. administration of PGDN to separate groups of animals resulted in an increase in cerebral blood flow that was correlated with the dose, but a clear dose-response was not obtained.

Bromocriptine-associated headache: possible life-threatening sympathomimetic interaction.

We present two cases of severe headache associated with the use of bromocriptine for lactation suppression in otherwise healthy women. In each case, the additional use of a therapeutic sympathomimetic agent resulted in extreme worsening of symptoms with development of hypertension and life-threatening complications (ventricular tachycardia and cardiac dysfunction in one case, seizures and cerebral vasospasm in the other). Sympathomimetics in combination with bromocriptine in patients with a bromocriptine-associated headache during the puerperium may be dangerous.

Cocaine-related vascular headaches.

The records of 21 patients admitted to hospital from January 1985 to December 1988 for acute headache associated with cocaine intoxication were reviewed. Fifteen patients were identified who experienced headaches with migrainous features in the absence of neurological or systemic complications. None of them had a history of cocaine-unrelated headaches or a family history of migraine, and all had a favourable outcome. Three possible mechanisms of cocaine-related vascular headaches are discussed which depend on the interval between cocaine ingestion and development of the headache. We postulate that acute headaches following cocaine use may relate to the sympathomimetic or vasoconstrictive effects of cocaine, while headaches following cocaine withdrawal or exacerbated during a cocaine "binge" may relate to cocaine-induced alteration of the serotoninergic system.

Studies on nitroglycerin and histamine provoked cluster headache attacks.

Attacks of cluster headache provoked by the administration of nitroglycerin (1 mg sublingually) or histamine (0.01 mg/kg subcutaneously) were studied. The constant latency time in individual patients during nitroglycerin and histamine provocation suggested that the same mechanism is involved in both methods of headache induction. Repeated nitroglycerin provocation revealed its tendency to lengthen duration of the refractory period at the end of the bout, when the attacks were less frequent. The "cross studies" on spontaneous and nitroglycerin provoked attacks indicated that the underlying mechanism of both is at least partially the same.

The relationship between vascular headaches and low-dose oral contraceptives.

The relationship between migraineous headaches and the use of low-dose oral contraceptives, the monophasic Rigevidon and the biphasic Anteovin, has been examined. In the examined cases Anteovin of higher oestrogen content provoked more vascular cephalalgias than Rigevidon with it's lower oestrogen content. In one part of the cases both pills even had therapeutic effects. According to the opinion of the author classical migraine means a relative contra-indication of hormonal contraception and is a serious adverse effect requiring the discontinuance of oral contraception. The headaches develop during the adaptational period of oral contraception and the migraineous attacks occur in the premenstrual period or at the beginning of menstruation which refer to an oestrogen withdrawal character. It may be supposed that vasoconstriction of certain extent, which has existed during the use of the pills, changes over to relative vasodilatation in this period and the extent of the changes is dependent on the oestreogen content of the tablets.

PIP: This article reports on a study concerning the relationship between migraine headaches and the use of the low-dose oral contraceptives Rigevidon and Anteovin. The objective was to examine how hormonal contraception influences vascular headaches and to what extent does it provoke such complaints. The study involved 138 and 441 women taking Rigevidon and Anteovin, respectively, 7.9-10.1% of whom already suffered from migraine headaches before taking the pill. Researchers observed the time of the development of the migrainous attack, its duration and intensity, and its course during each cycle. In the event of very intense headaches, the researchers changed the oral contraceptive to Ovidon or Continuin, or discontinued treatment (treatment was also discontinued in cases of increases in blood pressure). Of the women already suffering from headaches prior to taking the oral contraceptives, most of them suffered from a typical menstrual migraines caused by premenstrual syndrome which lasted for 2-4 days. The study found that the women on Rigevidon were less likely to suffer from vascular headaches than the women on Anteovin. While Anteovin caused classic migraine headaches on 0.98% of the women and atypical migraine headaches on 2.3% for the women, the figures were only 0.7% and 1.4% for women on Rigevidon. Researchers attribute these differences to the fact that Anteovin has a higher oestrogen content than Rigevidon. While the study does not explain the correlation between low-dose oral contraceptives and vascular headaches, it does point out the risk associated with oestrogen.

[Headaches in female workers in the rubber industry exposed to benzene vapors]. / Bóle glowy u pracownic przemyslu gumowego narazonych na pary benzyny.

173 female workers of the Rubber Plant "Stomil" exposed to petrol vapours, have been examined neurologically. The workers complained particularly often of vasomotor headaches which appeared to be much more frequent in petrol vapours-exposed workers, as compared to controls. On the other hand, subjects' age and length of employment did not affect significantly the prevalence of headache.

Trigeminal control of cranio-facial vasomotor response: I. Histamine test in patients with unilateral gasserian ganglion lesions.

It has been hypothesized that the trigeminal system may control vasomotor changes and pain in vascular headaches. In this study, headache was induced by an intravenous injection of histamine in 37 patients with trigeminal rhizotomy and in 12 controls. The vasomotor response to histamine was studied with facial telethermography. The headache in patients with trigeminal lesions differed, in a prevalence of unilateral localization contralaterally to the operated side (21 patients), from that in controls. No relationship was found between the hypoesthesia caused by the operation and the prevalence of unilateral headache. A statistically significant correlation (p less than 0.001) was found between unilateral absence of headache and decreased vasomotor response on the operated side. These reactions occurred more in patients who underwent thermocoagulation than in patients who underwent retro-gasserian rhizotomy. Thus the gasserian ganglion seems to control the cranio-facial vasomotor response and the headache through a vascular pathway, acting on cerebral arteries, which differs from the sensory pathway.

Effect of histamine on regional cerebral blood flow in man.

Regional cerebral blood flow (rCBF) was measured using the intra-arterial 133Xe technique in 35 or 256 areas of a hemisphere. In seven patients rCBF was measured in the resting state and following intracarotid (i.c.) infusion of histamine 10-50 microgram/min. In four patients histamine was infused intravenously in a dose of 25-40 microgram/min. Histamine caused no significant change in mean arterial blood pressure or arterial PCO2. There was no significant change in mean hemispheric blood flow during i.v. or i.c. histamine infusion. No change in the regional distribution of hemispheric blood flow was observed. Experimental histamine headache is most likely of extracranial origin.