Receptor systems mediating c-fos expression within trigeminal nucleus caudalis in animal models of migraine

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.