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Animal models of migraine have been widely used during the last decades to provide clues for understanding mechanisms underlying pathophysiology of migraine attacks and for developing specific therapeutic agents. They can be grouped into two main types: vascular and neurovascular. Trigemino-vascular system (TVS) is the most relevant efferent component and the mediators of its activity have been thoroughly studied along with some of the receptors involved to characterize anatomical and functional aspects of the system and to test efficacy and mechanisms of therapeutic agents. Neurovascular models are numerous. Plasma protein extravasation (PPE) model consists of measuring the amount of proteins leaking from vessels when TVS is either electrically or chemically stimulated and evaluating its blockade by systemically administered therapeutic agents of which specific receptors have also been identified. Activation of trigeminal nucleus caudalis (TNC) through meningeal stimulation of the superior sagittal sinus served to better understand the mechanisms of central nociceptive pathway. The cortical spreading depression (CSD) model has been used to activate the TVS through application of potassium chloride and evaluate Fos expression in the trigeminal nucleus caudalis (TNC). Finally, neurochemical, cerebrovascular, and nociceptive response to systemic or central administration of nitric oxide (NO) donors served to study central nociceptive pathway and autonomic response interaction. Transgenic mouse expressing human migraine mutations has been genetically engineered to provide an understanding of familial hemiplegic migraine (FHM). Animal models of migraine also served to better understand the role of hormones, genes, and environmental factors on migraine pathophysiology., (© 2022. Fondazione Società Italiana di Neurologia.)

Objective: To search for differences in prevalence of a CACNA1E variant between migraine without aura, various phenotypes of migraine with aura, and healthy controls., Background: Familial hemiplegic migraine type 1 (FHM1) is associated with mutations in the CACNA1A gene coding for the alpha 1A (Ca v 2.1) pore-forming subunit of P/Q voltage-dependent Ca 2+ channels. These mutations are not found in the common forms of migraine with or without aura. The alpha 1E subunit (Ca v 2.3) is the counterpart of Ca v 2.1 in R-type Ca 2+ channels, has different functional properties, and is encoded by the CACNA1E gene., Methods: First, we performed a total exon sequencing of the CACNA1E gene in three probands selected because they had no abnormalities in the three FHM genes. In a patient suffering from basilar-type migraine, we identified a single nucleotide polymorphism (SNP) in exon 20 of the CACNA1E gene (Asp859Glu - rs35737760; Minor Allele Frequency 0.2241) hitherto not studied in migraine. In a second step, we determined its occurrence in four groups by direct sequencing on blood genomic DNA: migraine patients without aura (N = 24), with typical aura (N = 55), complex neurological auras (N = 19; hemiplegic aura: N = 15; brain stem aura: N = 4), and healthy controls (N = 102)., Results: The Asp859Glu - rs35737760 SNP of the CACNA1E gene was present in 12.7% of control subjects and in 20.4% of the total migraine group. In the migraine group it was significantly over-represented in patients with complex neurological auras (42.1%), OR 4.98 (95% CI: 1.69-14.67, uncorrected P = .005, Bonferroni P = .030, 2-tailed Fisher's exact test). There was no significant difference between migraine with typical aura (10.9%) and controls., Conclusions: We identified a polymorphism in exon 20 of the CACNA1E gene (Asp859Glu - rs35737760) that is more prevalent in hemiplegic and brain stem aura migraine. This missense variant causes a change from aspartate to glutamate at position 859 of the Ca v 2.3 protein and might modulate the function of R-type Ca 2+ channels. It could thus be relevant for migraine with complex neurological aura, although this remains to be proven., (© 2017 American Headache Society.)

Context: The substantial functional impairment associated with migraine has both physical and emotional ramifications. Mood disorders are often comorbid in patients with migraine and are known to adversely affect migraine activity., Objectives: To explore the effects of osteopathic manipulative therapy (OMTh; manipulative care provided by foreign-trained osteopaths) on pain and mood disorders in patients with high-frequency migraine., Methods: Retrospective review of the medical records of patients with high-frequency migraine who were treated with OMTh at the Headache Istituto di Ricovero e Cura a Carattere Scientifico Fondazione Santa Lucia from 2011 to 2015. Clinical assessments were made using the Headache Disability Inventory (HDI), the Headache Impact Test (HIT-6), the Hamilton Depression Rating Scale (HDRS), and the State-Trait Anxiety Inventory (STAI) forms X-1 and X-2., Results: Medical records of 11 patients (6 women; mean age, 47.5 [7.8] years) with a diagnosis of high-frequency migraine who participated in an OMTh program met the inclusion criteria and were included in the study. When the questionnaire scores obtained at the first visit (T0) and after 4 OMTh sessions (T1) were compared, significant improvement in scores were observed on STAI X-2 (T0: 43.18 [2.47]; T1: 39.45 [2.52]; P<.05), HIT-6 (T0: 63 [2.20]; T1: 56.27 [2.24]; P<.05), and HDI (T0: 58.72 [6.75]; T1: 45.09 [7.01]; P<.05)., Conclusion: This preliminary study revealed that patients with high-frequency migraine and comorbid mood disorders showed significant improvement after four 45-minute OMTh sessions. Further investigation into the effects of OMTh on pain and mood disorders in patients with high-frequency migraine is needed.

Despite intensive neurophysiological research, evidence is lacking to show whether abnormal cortical excitability in migraine reflects a primary cortical disturbance or reduced control by thalamo-cortical loops. One way to contribute to the scientific discussion on this topic is to deliver transcranial magnetic stimulation (TMS) and test the cortical silent period (SP) recorded in facial muscles. The facial-muscle SP is a purely cortical phenomenon that reflects the excitability of inhibitory interneurons, and can disclose changes in cortical inhibition even in patients without documented primary lesions of the motor cortices. To test the interictal excitability of cortical motor inhibitory interneurons in migraine, we investigated the facial-SP in patients with migraine with and without aura between attacks. In 26 patients and 15 age-matched controls, high-intensity magnetic stimuli were delivered with a round coil centered at the vertex during a maximal muscle contraction. Electromyographic responses were recorded from surface electrodes placed over the subjects' perioral muscles. Facial SPs were significantly shorter in patients than in controls. The SP shortening provides neurophysiological evidence showing hypoexcitability of cortical inhibitory neurons in patients with migraine between attacks. Despite a possible primary deficit of cortical inhibitory interneurons in migraine, we favor the interpretation of a secondary disfacilitation by hypoactive thalamo-cortical loops. Based on this interpretation, the interictal reduced cortical inhibition documented by the shortened SP could be considered the motor counterpart of the reduced preactivation excitability level in the sensory cortices purported to explain why cortical evoked responses habituate poorly in patients with migraine.

The huge amount of data regarding triptans in clinical practice provides a great opportunity to learn about their efficacy, tolerability and adverse events and offers to the clinician the background for the best treatment option in any patient, given that the patient is suitable for being treated with any of those compounds. A detailed clinical history is necessary in order to make a preliminary selection of triptan-suitable or -unsuitable migraine patients. Among the former, a secondary selection may be made, to recognise different attacks that can be successfully treated with different triptans, according to attack presentation and progression, within the same patient. Reading single original articles has become very difficult. Therefore, data are often presented in review form, which may be too partial or oriented. Systematic reviews or meta-analyses better serve to comment on data as they follow an analytic method that is based upon pooling data from original articles and comparing them using statistical aids.

Objective: To investigate the response to sumatriptan in migraineurs with unilateral cranial autonomic symptoms such as lacrimation, eye redness, eyelid edema, nasal congestion, and rhinorrhea., Background: Given the potential large-scale recruitment of peripheral neurovascular 5-HT1B/1D receptors consequent to the activation of the trigeminal autonomic reflex in such patients, the presence of unilateral cranial autonomic symptoms may predict a positive response to sumatriptan., Methods: Seventy-two consecutive migraineurs with unilateral cranial autonomic symptoms were given sumatriptan 50-mg tablets to treat 1 migraine attack and were asked to record their clinical response to the drug at different time points. End points were pain-relief and pain-free response at 1 and 2 hours., Results: Pain relief was reported by 47 patients (65.3%) at 1 hour and by 59 (81.9%) at 2 hours. Pain-free response was reported by 22 patients (30.6%) at 1 hour and by 44 (61.1%) at 2 hours. Responsiveness to sumatriptan did not correlate with the type or number of unilateral cranial autonomic symptoms, demographic characteristics, prophylactic treatments, use of contraceptives, or concomitant tension-type headache., Conclusions: Migraineurs with unilateral cranial autonomic symptoms seem to respond to sumatriptan better than other migraineurs. The presence of unilateral cranial autonomic symptoms may predict a positive response to the triptans.

The electrically elicited corneal reflex is a useful tool for exploring the trigeminal system in humans and it may provide additional evidence pointing to a dysfunction of this system in migrainous patients. Tactile perception, corneal reflex and pain thresholds were studied in 48 migraine without aura patients during pain-free periods and compared with those observed in 24 controls. Twenty-eight of the patients had strictly unilateral headache, while the other 20 had bilateral or side-shifting pain during attacks. Both migraine subgroups (bilateral and unilateral) showed significantly lower thresholds compared with controls. The lowest values were observed on the symptomatic side of unilateral migraine patients. These findings suggest that sensorimotor mechanisms and/or pain control systems at the trigeminal level are impaired in migraine. The bilateral location of these abnormalities seems to point to a centrally located dysfunction.