Functional immunohistochemistry of neuropeptides and nitric oxide synthasein the nerve fibers of the supratentorial dura mater in an experimental migraine model

The supratentorial cerebral dura of the albino rat is equipped with a rich sensory innervation both in the connective tissue and around blood vessels, which includes nociceptive axons and their terminals; these display intens e calcitonin gene-related peptide (CGRP) immunoreactivity. Stereotactic ele ctrical stimulation of the trigeminal (Gasserian) ganglion, regarded as an experimental migraine model, caused marked increase and disintegration of c lub-like perivascular CGRP-immunopositive nerve endings in the dura mater a nd induced an apparent increase in the lengths of CGRP-immunoreactive axons . Intravenous administration of sumatriptan or eletriptan, prior to electri cal stimulation, prevented disintegration of perivascular terminals and ind uced accumulation of CGRP in terminal and preterminal portions of periphera l sensory axons. Consequently, immunopositive terminals and varicosities in creased in size; accumulation of axoplasmic organelles resulted in the "hol low" appearence of numerous varicosities. Since triptans exert their anti-m igraine effect by virtue of agonist action on 5-HT1D/B receptors, we sugges t that these drugs prevent the release of CGRP from perivascular nerve term inals in the dura mater by an action at 5-HT1D/B receptors. Nitroglycerine (NitroPOHL), given subcutaneously to rats, induces increased beading of nit ric oxide synthase (NOS)-immunoreactive nerve fibers in the supratentorial cerebral dura mater, and an apparent increase in the number of NOS-immunore active nerve fibers in the dural areas supplied by the anterior and middle meningeal arteries, and the sinus sagittalis superior. Structural alteratio ns of nitroxidergic axons innervating blood vessels of the dura mater suppo rt the idea that nitric oxide (NO) is involved in the induction of headache , a well-known side effect of coronary dilator agents. (C) 2001 Wiley-Liss, Inc.