Migraine pain, meningeal inflammation, and mast cells

Headache Research Laboratory, Department of Anesthesia, Critical Care and Pain Medicine, Beth Israel Deaconess Medical Center, 330 Brookline Avenue, E/CLS639, Boston, MA 02215, USA.
Current Pain and Headache Reports (Impact Factor: 2.26). 06/2009; 13(3):237-40. DOI: 10.1002/ddr.20208
Source: PubMed


Migraine pain has been attributed to an episode of local sterile meningeal inflammation and the subsequent activation of trigeminal primary afferent nociceptive neurons that supply the intracranial meninges and their related large blood vessels. However, the origin of this inflammatory insult and the endogenous factors that contribute to the activation of meningeal nociceptors remain largely speculative. A particular class of inflammatory cells residing within the intracranial milieu, known as meningeal mast cells, was suggested to play a role in migraine pathophysiology more than five decades ago, but until recently the exact nature of their involvement remained largely unexplored. This review examines the evidence linking meningeal mast cells to migraine and highlights current experimental data implicating these immune cells as potent modulators of meningeal nociceptors' activity and the genesis of migraine pain.

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    • "Migraine physiopathology is still largely unknown. Previous evidence has implicated inflammation in migraine predisposition [1]. Recently, obesity has also been associated with higher risk of migraine, worse migraine prognosis, more frequent and severe crises [2] [3]. "
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    ABSTRACT: Inflammatory mediators, including adipokines, have been studied in migraine pathophysiology; however, their role is not yet well established. The aim of the present study was to investigate adiponectin (ADP) and its association with clinical parameters and psychiatric comorbidities in migraine patients compared with controls. This was a cross sectional study including migraine patients and controls. Beck depression and anxiety inventories, Headache impact test, and Allodynia symptom checklist were recorded. Adiponectin was measured by ELISA. Sixty-eight migraine patients and sixty-five controls without headache were included. The ADP levels were significantly higher among patients with migraine (43.6±11.8 versus 36.6±9.7ng/mL, P<0.0001). Adiponectin levels were not correlated with depression and anxiety scores, as well as with migraine severity and allodynia scores. ADP levels were raised in migraine, independently of psychiatric comorbidities, migraine impact, and allodynia.
    Journal of the neurological sciences 04/2014; 342(1-2). DOI:10.1016/j.jns.2014.04.035 · 2.47 Impact Factor
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    • "Notably, there is an important difference in the local cellular environment regulating blood flow in cortex and in meninges: astrocytes control cortical (and pial) blood flow via their end feet that adhere to the vessel wall to form blood-brain barrier [34], [35], but such glial control is missing in dura mater vessels. Oppositely, dura mater is enriched with mast cells [36], and as GTN presumably degranulates mast cells [37], this could explain the vasoconstriction induced by this agent. Our preliminary unpublished data indicate strong vasoconstrictor effect in meninges induced by mast cell degranulating compounds (these pilot experiments will constitute the core of a future study). "
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    ABSTRACT: Vascular changes underlying headache in migraine patients induced by Glyceryl trinitrate (GTN) were previously studied with various imaging techniques. Despite the long history of medical and experimental use of GTN, its effects on the brain vasculature are still poorly understood presumably due to low spatial resolution of the imaging modalities used so far. We took advantage of the micrometer-scale vertical resolution of two-photon microscopy to differentiate between the vasodynamic effects of GTN on meningeal versus cortical vessels imaged simultaneously in anesthetized rats through either thinned skull or glass-sealed cranial window. Intermediate and small calibre vessels were visualized in vivo by imaging intravascular fluorescent dextran, and detection of blood flow direction allowed identification of individual arterioles and venules. We found that i.p.-injected GTN induced a transient constriction of meningeal arterioles, while their cortical counterparts were, in contrast, dilated. These opposing effects of GTN were restricted to arterioles, whereas the effects on venules were insignificant. Interestingly, the NO synthase inhibitor L-NAME did not affect the diameter of meningeal vessels but induced a constriction of cortical vessels. The different cellular environment in cortex versus meninges as well as distinct vessel wall anatomical features probably play crucial role in the observed phenomena. These findings highlight differential region- and vessel-type-specific effects of GTN on cranial vessels, and may implicate new vascular mechanisms of NO-mediated primary headaches.
    PLoS ONE 02/2014; 9(2):e89699. DOI:10.1371/journal.pone.0089699 · 3.23 Impact Factor
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    • "The observations of this study, taken with the observations of (Shen et al., 2013), point to a possible role of the meninges in the pathophysiology of autism. Once thought to be of little significance to cortical pathology, newer observations indicate the meninges participate in migraine (Levy, 2009), and potential contribute to multiple sclerosis (Gardner et al., 2013). The Gardner group from Imperial College in London hypothesized that pro-inflammatory cytokine production within the meninges may be a key to the demyelination model they created for multiple sclerosis. "
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    ABSTRACT: Background: Autism spectrum disorders (ASDs) are developmental conditions of uncertain etiology which have now affected more than 1% of the school-age population of children in many developed nations. Transcranial ultrasonography (TUS) via the temporal bone appeared to be a potential window of investigation to determine the presence of both cortical abnormalities and increased extra-axial fluid (EAF). Methods: TUS was accomplished using a linear probe (10–5 MHz). Parents volunteered ASD subjects (N = 23; males 18, females 5) for evaluations (mean = 7.46 years ± 3.97 years), and 15 neurotypical siblings were also examined (mean = 7.15 years ± 4.49 years). Childhood Autism Rating Scale (CARS2®) scores were obtained and the ASD score mean was 48.08 + 6.79 (Severe). Results: Comparisons of the extra-axial spaces indicated increases in the ASD subjects. For EAF we scored based on the gyral summit distances between the arachnoid membrane and the cortical pia layer (subarachnoid space): (1) <0.05 cm, (2) 0.05–0.07 cm, (3) 0.08–0.10 cm, (4) >0.10 cm. All of the neurotypical siblings scored 1, whereas the ASD mean score was 3.41 ± 0.67. We also defined cortical dysplasia as the following: hypoechoic lesions within the substance of the cortex, or disturbed layering within the gray matter. For cortical dysplasia we scored: (1) none observed, (2) rare hypoechogenic lesions and/or mildly atypical cortical layering patterns, (3) more common, but separated areas of cortical hypoechogenic lesions, (4) very common or confluent areas of cortical hypoechogenicity. Again all of the neurotypical siblings scored 1, while the ASD subjects’ mean score was 2.79 ± 0.93. Conclusion: TUS may be a useful screening technique for children at potential risk of ASDs which, if confirmed with repeated studies and high resolution MRI, provides rapid, non-invasive qualification of EAF, and cortical lesions.
    Frontiers in Human Neuroscience 01/2014; 7:934. DOI:10.3389/fnhum.2013.00934 · 2.99 Impact Factor
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