Dd. Mitsikostas et Ms. Del Rio, Receptor systems mediating c-fos expression within trigeminal nucleus caudalis in animal models of migraine, BRAIN RES R, 35(1), 2001, pp. 20-35
In intracranial structures unmyelinated C- and A delta -fibers of the trige
minal nerve transmit pain stimuli from meninges to the trigeminal nucleus c
audalis (Sp5C). Peripheral nerve endings surround meningeal vessels (the so
-called trigeminovascular system) and contain vasoactive neuropeptides (cal
citonin gene-related peptide, substance P and neurokinin A). Activation of
the trigeminovascular system promotes a meningeal sterile inflammatory resp
onse through the release of neuropeptides by peripheral endings. Orthodromi
c conduction along trigeminovascular fibers transmits information centrally
with induction of immediate early c-fos gene within post-synaptic Sp5C neu
rons, as a marker of neuronal activity within central nociceptive pathways.
In laboratory animals the system is activated by either electrical stimula
tion of the TG, chemical stimulation of the meninges, electrical or mechani
cal stimulation of the superior sagittal sinus or by induction of cortical
spreading depression. All these techniques induce c-fos within SD5C and are
used as a rodent/feline model of vascular headache in humans. Up-to-date t
here is evidence that at least ten receptors (5-HT1B, 5-HT1D, 5-HT1F, 5-HT2
B, NK-1, GABA(A), NMDA, AMPA, class III metabotropic glutamate receptors, a
nd opioids mu receptors) modulate c-fos expression within Sp5C. These recep
tors represent potential targets for anti-migraine drugs as shown by tripta
ns (5-HT1B/1D/1F) and ergot alkaloids (5-PIT1A1B/1D/1F). This review discus
ses the importance of c-Sos expression within Sp5C as a marker of cephalic
nociception, the different cephalic pain models that induce c-fos within Sp
5C, the receptors involved and their potential role as targets for anti-mig
raine drugs. (C) 2001 Elsevier Science B.V. All rights reserved.