Dural administration of inflammatory soup or Complete Freund's Adjuvant induces activation and inflammatory response in the rat trigeminal ganglion.
BACKGROUND
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 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.


METHODS
We 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.


RESULTS
Both 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.


CONCLUSIONS
These 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.
Department of Medicine, Institute of Clinical Sciences, Division of Experimental Vascular Research, Lund University, Sölvegatan 17, SE 221 84, Lund, Sweden.
M
M
Lukács
K A
KA
Haanes
Zs
Z
Majláth
J
J
Tajti
L
L
Vécsei
K
K
Warfvinge
L
L
Edvinsson
D000818:Animals; D004388:Dura Mater / Q000187:drug effects / Q000378:metabolism*; D005620:Freund's Adjuvant / Q000008:administration & dosage* / Q000633:toxicity*; D007249:Inflammation / Q000139:chemically induced / Q000378:metabolism; D018836:Inflammation Mediators / Q000378:metabolism*; D008297:Male; D008881:Migraine Disorders / Q000139:chemically induced / Q000378:metabolism; D009412:Nerve Fibers / Q000187:drug effects / Q000378:metabolism; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D010146:Pain / Q000139:chemically induced / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012668:Trigeminal Ganglion / Q000187:drug effects / Q000378:metabolism*
D018836:Inflammation Mediators; D005620:Freund's Adjuvant