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J Cereb Blood Flow Metab. 2017 Jan 1:271678X17747188. doi: 10.1177/0271678X17747188. [Epub ahead of print]

Perivascular neurotransmitters: Regulation of cerebral blood flow and role in primary headaches.

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1 Department of Clinical Experimental Research, Glostrup Research Institute, 70590 Rigshospitalet Glostrup , Glostrup, Denmark.
2 Division of Experimental Vascular Research, Department of Clinical Sciences, 70590 Lund University , Lund, Sweden.


In order to understand the nature of the relationship between cerebral blood flow (CBF) and primary headaches, we have conducted a literature review with particular emphasis on the role of perivascular neurotransmitters. Primary headaches are in general considered complex polygenic disorders (genetic and environmental influence) with pathophysiological neurovascular alterations. Identified candidate headache genes are associated with neuro- and gliogenesis, vascular development and diseases, and regulation of vascular tone. These findings support a role for the vasculature in primary headache disorders. Moreover, neuronal hyperexcitability and other abnormalities have been observed in primary headaches and related to changes in hemodynamic factors. In particular, this relates to migraine aura and spreading depression. During headache attacks, ganglia such as trigeminal and sphenopalatine (located outside the blood-brain barrier) are variably activated and sensitized which gives rise to vasoactive neurotransmitter release. Sympathetic, parasympathetic and sensory nerves to the cerebral vasculature are activated. During migraine attacks, altered CBF has been observed in brain regions such as the somatosensory cortex, brainstem and thalamus. In regulation of CBF, the individual roles of neurotransmitters are partly known, but much needs to be unraveled with respect to headache disorders.


Blood–brain barrier; cerebral blood flow; migraine; parasympathetic nervous system; sympathetic nervous system


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