In this study, the relationship between hormonal-related events and migraine with aura (MA) and without aura (MO) was investigated. Subjects included 268 women suffering from MA (88) and MO (180). Data were collected on the relationship between sex-hormone-related events and migraine. Migraine during menses was observed in a significantly higher percentage of MO than MA patients (p < 0.03). Menstrual migraine was significantly more common in MO than in MA patients (p < 0.01). Migraine began during pregnancy in a significantly higher percentage of MA than of MO patients (p < 0.01). No significant difference was observed between the two groups of patients regarding the onset of migraine at menarche, after menopause, in the postpartum period or during the early cycles of oral contraceptives. Also, both groups of patients showed a similar migraine course during pregnancy, oral contraceptive use and menopause. Eight patients with coexisting migraine with aura and migraine without aura attacks reported the appearance of the aura symptom for the first time in the early cycles of oral contraceptive intake. These findings suggest that gonadal hormone fluctuation may influence both types of migraine.

No abstract

The endogenous cannabinoid anandamide (AEA) plays important roles in modulating pain. Head pain is an almost universal human experience, yet primary headache disorders, such as migraine without aura (MoA) or episodic tension-type headache (ETTH), can represent a serious threat to well-being when frequent and disabling. We assessed the discriminating role of endocannabinoids among patients with ETTH or MoA, and control subjects. We measured the activity of AEA hydrolase and AEA transporter, and the level of cannabinoid receptors in peripheral platelets from MoA, ETTH and healthy controls. Sixty-nine headache patients and 36 controls were selected. Diagnosis of headache type was made according to the International Headache Society criteria. We observed significant sex differences concerning AEA membrane transporter and fatty acid amide hydrolase activity in all groups. An increase in the activity of AEA hydrolase and AEA transporter was found in female but not male migraineurs. Cannabinoid receptors were the same in all groups. Here we show that the endocannabinoid system in human platelets is altered in female but not male migraneurs. Our results suggest that in migraineur women an increased AEA degradation by platelets, and hence a reduced concentration of AEA in blood, might reduce the pain threshold and possibly explain the prevalence of migraine in women. The involvement of the endocannabinoid system in migraine is new and broadens our knowledge of this widespread and multifactorial disease.

Cortex and periaqueductal grey (PAG) play a major role in the pathophysiology of migraine. Some antiepileptic drugs (AEDs) influence the activity of these structures by modulating high-voltage-activated (HVA) Ca(2+) channels and are effective in migraine prevention. The aim of the present study was to investigate the expression of total HVA Ca(2+) channels in cortical and PAG neurons and to study the differential action of AEDs on these channels. Isolated neurons were visually identified based on morphological criteria. HVA currents were recorded by whole-cell patch-clamp technique. The distribution ratio of L-, N-, P-, Q- and R-type HVA Ca(2+) channels was different between cortical and PAG neurons. In particular, we found that P- and Q-type HVA Ca(2+) channels were more expressed in PAG neurons than in cortical cells, whereas L- and R-type HVA Ca(2+) channels showed an opposite distribution. Interestingly, N-type HVA Ca(2+) channels were equally distributed in these two neuronal populations. A differential sensitivity to AEDs of HVA Ca(2+) channels located on cortical and PAG neurons was observed for topiramate (TPM), but not for lamotrigine (LTG) or levetiracetam (LEV). In fact, whereas both LTG and LEV were equally effective and potent in inhibiting HVA Ca(2+) currents in the two neuronal populations, TPM showed a much higher potency and efficacy in blocking these currents in PAG neurons than in cortical pyramidal cells. TPM, in fact, inhibited N-, P- and L-type channels in PAG neurons, whereas in cortical neurons this AED modulated only P- and L-type channels. Unlike the other AEDs investigated, valproic acid did not affect HVA Ca(2+) currents in cortical and PAG neurons. The negative modulation of specific subtypes of HVA Ca(2+) channels by various AEDs can restore normal electrical activity in target brain areas such as cortex and PAG, providing interesting therapeutic approaches in migraine prevention.

We evaluated the effect of l-deprenyl, a drug that increases the availability of endogenous dopamine, on the plasma levels of prolactin and growth hormone in 10 female patients with migraine and in 10 control subjects matched for age and menstrual phase. The patients showed a significant decrease in prolactin levels at 30, 60 and 120 min after the oral administration of 5 mg of l-deprenyl when compared with the values obtained in controls (p < 0.001). The effects of l-deprenyl on growth hormone plasma levels were not significantly different between patients and controls. These data suggest that l-deprenyl inhibits prolactin release in migraine patients, but not in control subjects. This differential sensitivity could be explained by dopamine receptor supersensitivity in migraine patients.