Abstract
BackgroundMigraine is a painful disorder with a huge impact on individual and public health. We hypothesize that migraine pain originates from a central mechanism that results secondarily in hypersensitivity in peripheral afferents associated with the cerebral and cranial blood vessels. It has previously been shown that application of inflammatory or algesic substances onto the dura mater or chemical stimulation of the dural receptive fields causes hypersensitivity to mechanical and thermal stimulation together with direct activation of the TG. We asked whether local inflammation of dura mater induces inflammatory activation in the trigeminal ganglion.MethodsWe performed topical administration of inflammatory soup (IS) or Complete Freund’s Adjuvant (CFA) onto an exposed area of the rat dura mater in vivo for 20 min. The window was closed and the rats were sacrificed after 4 h and up to 7 days. Myography was performed on middle meningeal arteries. The trigeminal ganglia were removed and processed for immunohistochemistry or Western blot.ResultsBoth CFA and IS induced enhanced expression of pERK1/2, IL-1β and CGRP in the trigeminal ganglia. The pERK1/2 immunoreactivity was mainly seen in the satellite glial cells, while IL-1β reactivity was observed in the neuronal cytoplasm, close to the cell membrane, seemingly as sign of neuro-glial interaction. The CGRP expression in the neurons and nerve fibres was enhanced after the application of either inflammatory agent. Myography resulted in a strong vasoconstrictor response to IS, but not to CFA.ConclusionsThese results suggest that the application of IS or CFA onto the dura mater causes long-term activation of the TG and demonstrate the importance of the neuro-glial interaction in the activation of the trigeminovascular system.Electronic supplementary materialThe online version of this article (doi:10.1186/s10194-015-0564-y) contains supplementary material, which is available to authorized users.
Highlights
Migraine is a painful disorder with a huge impact on individual and public health
Immunohistochemistry pERK1/2 pERK1/2 can be used as a dynamic, rapid and robust marker of noxious stimulation, as ERK1/2 phosphorylation can occur within a minute [21]
We were interested in the long term activation of pERK, as it could be related to permanent activation of the trigeminal ganglion (TG). pERK1/2 immunoreactivity was observed in a few nuclei and nucleoli of the neurons in the fresh TGs
Summary
Migraine is a painful disorder with a huge impact on individual and public health. We hypothesize that migraine pain originates from a central mechanism that results secondarily in hypersensitivity in peripheral afferents associated with the cerebral and cranial blood vessels. It has been shown that application of inflammatory or algesic substances onto the dura mater or chemical stimulation of the dural receptive fields causes hypersensitivity to mechanical and thermal stimulation and activation in the TG and in the brainstem trigeminal neurons [8,9,10,11]. We consider that this may serve as a suitable method for in vivo examination. In support of this view, infusion of nitroglycerine or local capsaicin onto the dura mater elicits increased extracellular signal-regulated kinase (ERK) phosphorylation in the meningeal arteries and TG [12, 13]
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