Chapter 7. The neurobiology of migraine

Handbook of Clinical Neurology 12/2010; 97:99-108. DOI: 10.1016/S0072-9752(10)97007-3
Source: PubMed


The understanding of migraine has moved well beyond its traditional characterization as a "vascular headache." In considering the basic neurobiology of migraine, it is important to begin with the concept of migraine as not merely a headache, but rather a heterogeneous array of episodic symptoms. Among the array of phenomena experienced by migraine patients are visual disturbances, nausea, cognitive dysfunction, fatigue, and sensitivity to light, sound, smell, and touch. These symptoms may occur independently or in any combination, and in some patients occur even in the absence of headache. The diversity and variability of symptoms experienced by migraine patients belies a complex neurobiology, involving multiple cellular, neurochemical, and neurophysiological processes occurring at multiple neuroanatomical sites. Migraine is a multifaceted neurobiological phenomenon that involves activation of diverse neurochemical and cellular signaling pathways in multiple regions of the brain. Propagated waves of cellular activity in the cortex, possibly involving distinct glial and vascular signaling mechanisms, can occur along with activation of brainstem centers and nociceptive pathways. Whether different brain regions become involved in a linear sequence, or as parallel processes, is uncertain. The modulation of brain signaling by genetic factors, and by sex and sex hormones, provides important clues regarding the fundamental mechanisms by which migraine is initiated and sustained. Each of these mechanisms may represent distinct therapeutic targets for this complex and commonly disabling disorder.

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    • "The symptoms include: severe headache, nausea, cognitive impairment, and discomfort from normal light, sound, and smells (Buse et al., 2012; Charles and Brennan, 2010; Goadsby et al., 2009; Noseda and Burstein, 2013; Woodhouse and Drummond, 1993). The migraine pathophysiology is not fully elucidated, though several brain circuits have been implicated (Goadsby et al., 2009; Noseda and Burstein, 2013). Auditory symptoms are prominent in migraine and are the focus of this study; they include fluctuating low-frequency hearing loss, sudden deafness, auditory hallucinations, tinnitus, and phonophobia. "
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    ABSTRACT: Migraine symptoms often include auditory discomfort. Nitroglycerin (NTG)-triggered central sensitization (CS) provides a rodent model of migraine, but auditory brainstem pathways have not yet been studied in this example. Our objective was to examine brainstem auditory evoked potentials (BAEPs) in rat CS as a measure of possible auditory abnormalities. We used four subdermal electrodes to record horizontal (h) and vertical (v) dipole channel BAEPs before and after injection of NTG or saline. We measured the peak latencies (PLs), interpeak latencies (IPLs), and amplitudes for detectable waveforms evoked by 8, 16, or 32 KHz auditory stimulation. At 8 KHz stimulation, vertical channel positive PLs of waves 4, 5, and 6 (vP4, vP5, and vP6), and related IPLs from earlier negative or positive peaks (vN1-vP4, vN1-vP5, vN1-vP6; vP3-vP4, vP3-vP6) increased significantly 2 hours after NTG injection compared to the saline group. However, BAEP peak amplitudes at all frequencies, PLs and IPLs from the horizontal channel at all frequencies, and the vertical channel stimulated at 16 and 32 KHz showed no significant/consistent change. For the first time in the rat CS model, we show that BAEP PLs and IPLs ranging from putative bilateral medial superior olivary nuclei (P4) to the more rostral structures such as the medial geniculate body (P6) were prolonged 2 hours after NTG administration. These BAEP alterations could reflect changes in neurotransmitters and/or hypoperfusion in the midbrain. The similarity of our results with previous human studies further validates the rodent CS model for future migraine research.
    Brain research 05/2014; 1563. DOI:10.1016/j.brainres.2014.03.033 · 2.84 Impact Factor
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    ABSTRACT: OPINION STATEMENT: Migraine is a biologic disorder of the brain characterized by a heterogeneous array of symptoms and episodes of disabling headache. By definition, such attacks last between 4 and 72 h without treatment, with the disability arising from a variety of factors including severe pain, gastrointestinal symptoms such as nausea or vomiting, and sensory sensitivities to light, noise, or odor. All these features may be exacerbated by stimulation, motion, or activity, often rendering the patient completely immobile. Although retreat and rest, coupled with local application of ice, may provide some measure of comfort, most of those with migraine hunt for therapeutic solutions. In designing acute headache treatment strategies, it is imperative for clinicians to recognize the variability between individuals in the frequency, intensity, and duration of attacks. Certain patients require more aggressive options. It is also crucial to identify the significant intra-individual variability of migraine; most patients describe an assortment of headaches of different intensities and time to disability. Less intense episodes, which patients often term sinus, tension, or regular headaches, usually represent milder versions of migraine, simplifying both diagnostic and therapeutic approaches. Evidence-based guidelines and clinical experience support the use of nonsteroidal anti-inflammatory drugs (NSAIDs) in the management of mild to moderate migraine attacks. Recommend migraine-specific agents (triptans and dihydroergotamine) when the attacks are more severe or have consistently failed to respond to the use of NSAIDs in the past. Encourage those with less frequent episodic migraine to use their acute agents at the earliest signs of headache. Advise those with frequent headache (>10 days per month) to limit acute treatments to only the most disabling episodes in order to avoid the "medication overuse" phenomenon. Consider rescue or back-up therapy. Do not use compounds containing butalbital or opiates (or place extreme limits on them), out of concern for progression to chronic migraine.
    Current Treatment Options in Neurology 02/2011; 13(1):15-27. DOI:10.1007/s11940-010-0107-4 · 1.94 Impact Factor
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    ABSTRACT: Basic and clinical neuroscience research findings suggest that cortical spreading depression (CSD) and epileptic foci may facilitate each other; furthermore, the threshold required for the onset of CSD has been suggested to be lower than that required for an epileptic focus. These data may explain the prevalence of epilepsy in migraine populations (ranging from 1% to 17%) and the frequency of migraine in epileptic populations (ranging from 8.4% to 20%). There is currently a considerable amount of confusion regarding this topic in both headache and epilepsy classifications (ICHD-II and ILAE). The ICHD-II includes "migraine-triggered seizure" (coded as "1.5.5") (so-called "migralepsy") among the "complications of migraine", and defines "hemicrania epileptica" ("7.6.1") as an "ictal headache" (ipsilateral to the ictal EEG discharge) that occurs "synchronously" with a seizure (partial epileptic seizure) recognized by ILAE classification. However, neither "migralepsy" nor "hemicrania epileptica" are terms used in the current ILAE classification. On the basis of data reported in the literature and our recent findings, we suggest that the terms "migraine-triggered seizure" and "migralepsy" be deleted until unequivocal evidence of the existence of these conditions emerges. "Ictal epileptic headache" (IEH) should be used to classify those rare events in which headache represents the sole ictal epileptic manifestation. On the other hand, the term "hemicrania epileptica" should be maintained in the ICHD-II and introduced into the ILAE, and be used to classify all cases in which an "ictal epileptic headache" "coexists" and is associated synchronously or sequentially with other ictal sensory-motor events.
    Seizure 03/2011; 20(4):271-5. DOI:10.1016/j.seizure.2011.02.012 · 1.82 Impact Factor
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