Our data support the hypothesis that altered tyrosine metabolism plays an important role in the pathogenesis of CM. The high plasma levels of TYR, a potent agonist of the trace amine associated receptors type 1 (TAAR1), may ultimately down-regulate this receptor because of loss of inhibitory presynaptic regulation, therein resulting in uncontrolled neurotransmitter release. This may produce functional metabolic consequences in the synaptic clefts of the pain matrix implicated in CM.
Migraine is often accompanied with signs of increased intracranial and extracranial mechanical sensitivities. The prevailing view today is that migraine headache is a neurovascular disorder with intracranial origin and involvement of meningeal blood vessels and their pain nerve fibers. Allodynia, defined as perception of pain following not painful stimulation, is a common clinical feature in various pain syndromes, and as part of migraine pain, it can be considered an indicator of trigeminal neural network sensitization. The cutaneous allodynia that accompanies the migraine headache in a large percentage of patients may be considered the clinical expression of central nervous system sensitization and is characterized by pain provoked by stimulation of the skin that would ordinarily not produce pain. An altered codification process of sensory impulses in the brainstem, in particular by the nucleus caudalis trigeminalis, may justify the temporal aspects and symptoms in the course of migraine attack.
In a multicentric, open, preliminary trial, we evaluated the use of ginkgolide B, a herbal constituent extract from Ginkgo biloba tree leaves, in the prophylactic treatment of migraine with aura (MA). Fifty women suffering from migraine with typical aura, or migraine aura without headache, diagnosed according to International Headache Society criteria, entered a six-month study. They underwent a two month run-in period free of prophylactic drugs, followed by a four month treatment period (subdivided into two bimesters, TI and TII) with a combination of 60 mg ginkgo biloba terpenes phytosome, 11 mg coenzyme Q 10, and 8.7 mg vitamin B2 (Migrasoll Ò ), administered twice daily. A detailed diary reporting neurological symptoms, duration, and frequency of MA was compiled by patients throughout the trial. The number of MA significantly decreased during treatment (from 3.7 ± 2.2 in the run-in period, to 2.0 ± 1.9 during TI and to 1.2 ± 1.6 during TII; Anova for repeated measures: P \ 0.0001).There was also a statistically significant decrease in the average MA duration, which was 40.4 ± 19.4 min during run-in, 28.2 ± 19.9 during TI, and 17.6 ± 20.6 during TII. Total disappearance of MA was observed in 11.1% patients during TI and in 42.2% of patients during T2. No serious adverse event was provoked by Migrasoll Ò administration. Ginkgolide B is effective in reducing MA frequency and duration. The effect is clearly evident in the first bimester of treatment and is further enhanced during the second.
An association between obesity and migraine has been observed in recent studies and it is supported by plausible biological mechanisms. The objective of this study is to evaluate the efficacy of frovatriptan and other triptans in the acute treatment of migraine, in patients enrolled in three randomized, double-blind, crossover, Italian studies and classified according to body mass index (BMI) levels, as normal weight or non-obese (NO, BMI 18.5-24.9 kg/m(2)) and overweight or obese subjects (O, BMI ≥ 25 kg/m(2)). 414 migraineurs with or without aura were randomized to frovatriptan 2.5 mg or rizatriptan 10 mg (study 1), frovatriptan 2.5 mg or zolmitriptan 2.5 mg (study 2), frovatriptan 2.5 mg or almotriptan 12.5 mg (study 3). After treating up to three episodes of migraine in 3 months with the first treatment, patients switched to the alternate treatment for the next 3 months. The present analysis assessed triptan efficacy in 220 N and in 109 O subjects of the 346 individuals of the intention-to-treat population. The proportion of pain free at 2 h did not significantly differ between frovatriptan and the comparators in either NO (30 vs. 34 %) or O (24 vs. 27 %). However, the rate of pain free at 2 h was significantly (p < 0.05) larger in NO than in O, irrespective of the type of triptan. Pain relief at 2 h was also similar between drug treatments for either subgroup. Pain relapse occurred at 48 h in significantly (p < 0.05) fewer episodes treated with frovatriptan in both NO (26 vs. 36 %) and O (27 vs. 49 %). The rate of 48-h relapse was similar in NO and O with frovatriptan, while it was significantly (p < 0.05) higher in O with the comparators. Frovatriptan, in contrast to other triptans, retains a sustained antimigraine effect in NO and even more so in O subjects.
Migraine is a prevalent, disabling, undiagnosed and undertreated disease in neurological practice. It is a chronic, recurrent disorder with episodic manifestations that are progressive in some individuals with clinical, physiological and anatomical bases. Progression may be due to mechanisms generating the migraine attacks or to the activation generated by the attacks. Potentially remediable risk factors for chronification include frequency of migraine attacks, obesity, excessive use of medications, caffeine overuse, stressful life events, depression, sleep disorders and cutaneous allodynia.
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