Correlate Of Migraine Aura Research Articles

PACAP-PAC1 receptor inhibition is effective in opioid induced hyperalgesia and medication overuse headache models

Opioids prescribed for pain and migraine can produce opioid-induced hyperalgesia (OIH) or medication overuse headache (MOH). We previously demonstrated that pituitary adenylate cyclase activating polypeptide (PACAP) is upregulated in OIH and chronic migraine models. Here we determined if PACAP acts as a bridge between opioids and pain chronification. We tested PACAP-PAC1 receptor inhibition in novel models of opioid-exacerbated trigeminovascular pain. The PAC1 antagonist, M65, reversed chronic allodynia in a model which combines morphine with the migraine trigger, nitroglycerin. Chronic opioids also exacerbated cortical spreading depression, a correlate of migraine aura; and M65 inhibited this augmentation. In situ hybridization showed MOR and PACAP co-expression in trigeminal ganglia, and near complete overlap between MOR and PAC1 in the trigeminal nucleus caudalis and periaqueductal gray. PACAPergic mechanisms appear to facilitate the transition to chronic headache following opioid use, and strategies targeting this system may be particularly beneficial for OIH and MOH.

Migraine : Evolution of a Common Disorder

MIGRAINE is a common, chronic, incapacitating neurovascular disorder, characterized by attacks of severe headache, autonomic nervous system dysfunction, and in some patients, an aura involving neurologic symptoms. In one-third of patients the headache is preceded by transient neurological symptoms that are most frequently visual but may involve other senses and speech [migraine with aura (MA)]. Migraine is extremely prevalent [affecting 17% of females and 8% of men], very expensive ($18.5 billion Euros per year in Europe], and disabling [one of the World Health Organization's top 20 most disabling disorders]. It is consequently a public fitness hassle of exceptional effect on each the man or woman and society. Most migraine assaults begin with inside the mind, as advised through (a) the premonitory signs (e.g., issue with speech and reading, expanded emotionality, sensory hypersensitive reaction) that during many sufferers are exceptionally predictive of the attack, even though such signs arise as much as 12 h earlier than the attack, and through (b) the character of a few usual migraine triggers which includes stress, sleep deprivation, oversleeping, hunger, and extended sensory stimulation. Psychophysical and neurophysiological research have supplied clean proof that with inside the duration among assaults migraines display hypersensitive reaction to sensory stimuli and odd processing of sensory information, characterized through expanded amplitudes and decreased habituation of evoked and event-associated potentials. It is usually believed that migraine headache relies upon at the activation and sensitization of the trigeminovascular ache pathway and that cortical spreading depression (CSD) is the neurophysiological correlate of migraine aura. CSD may be precipitated in animals through focal stimulation of the cerebral cortex and includes a slowly propagating (2–6 mm min−1) wave of robust neuronal and glial depolarization; the mechanisms of initiation and propagation of CSD continue to be unclear. The mechanisms of the number one mind dysfunction(s) main to the onset of a migraine attack, to CSD susceptibility, and to episodic activation of the trigeminovascular ache pathway continue to be in large part unknown and the predominant open problem with inside the neurobiology of migraine.

Cortical Mechanisms of Single-Pulse Transcranial Magnetic Stimulation in Migraine

Single-pulse transcranial magnetic stimulation (sTMS) of the occipital cortex is an effective migraine treatment. However, its mechanism of action and cortical effects of sTMS in migraine are yet to be elucidated. Using calcium imaging and GCaMP-expressing mice, sTMS did not depolarise neurons and had no effect on vascular tone. Pre-treatment with sTMS, however, significantly affected some characteristics of the cortical spreading depression (CSD) wave, the correlate of migraine aura. sTMS inhibited spontaneous neuronal firing in the visual cortex in a dose-dependent manner and attenuated l-glutamate-evoked firing, but not in the presence of GABAA/B antagonists. In the CSD model, sTMS increased the CSD electrical threshold, but not in the presence of GABAA/B antagonists. We first report here that sTMS at intensities similar to those used in the treatment of migraine, unlike traditional sTMS applied in other neurological fields, does not excite cortical neurons but it reduces spontaneous cortical neuronal activity and suppresses the migraine aura biological substrate, potentially by interacting with GABAergic circuits.

Genetics of Migraine: An Update

An important genetic component of migraine was systematically established by epidemiological studies in the 1990s. Over the past 15 years, significant progress has been made in unraveling the genetic basis and pathophysiological mechanisms of familial hemiplegic migraine, a rare and severe autosomal-dominant subtype of migraine with aura. Three different causative genes (CACNA1A, ATP1A2 and SCN1A), all of which are involved in cerebral ion translocation, have been identified. Functional studies and mouse models have shown that mutations in these genes, by different mechanisms, cause a disturbed cerebral glutamate homeostasis and, thus, increase susceptibility to cortical spreading depression, the likely correlate of migraine aura. More recently, genome-wide association studies have, for the first time, detected robust risk variants associated with the more common, genetically complex types of migraine, which has generated new perspectives for genetic research in migraine. This review summarizes the current knowledge about migraine genetics, with a focus on both familial hemiplegic migraine and recent results of genome-wide association studies.

Genetik der Migräne

Twin and family studies provide evidence of a genetic component in migraine, in particular migraine with aura (MA). Familial hemiplegic migraine (FHM) is a rare monogenic subtype of MA for which three causative genes have been identified: CACNA1A (FHM1), ATP1A2 (FHM2), and SCN1A (FHM3). Mutations in these genes are also found in some patients with sporadic hemiplegic migraine. Linkage studies have identified several gene loci for the more common forms of migraine; however, identification of the respective causative genes is still pending. This review summarizes recent developments in the genetics of migraine and their implications for molecular genetic testing. We further discuss the roles of CACNA1A, ATP1A2, and SCN1A in the pathophysiology of cortical spreading depression, which is the likely correlate of migraine aura.

Sleeping behaviour and headache attacks in cases of primary headache. Possible pathological mechanisms

Headache is connected with sleep quality, e.g. hypnic headache and chronic paroxysmal headache attacks occur preferentially during REM sleep; this is possibly also true for cluster headache and migraine. REM sleep is typically characterized by the occurrence of ponto-geniculo-occipital spikes (PGOs). These PGOs should be able to trigger cortical spreading depression (CSD), which, although often clinically silent, is assumed to be an essential element of a migraine attack and possibly also of other forms of headache. CSDs are considered a correlate of migraine aura. They could lead to the secondary activation of trigeminovascular afferences, which would then induce a headache. Interestingly, illnesses that are comorbid with migraine cause an increase in the amount of REM sleep; conversely, various drugs administered prophylactically for these illnesses reduce the quantity of REM sleep.