The results will contribute to the understanding of the pathogenesis of primary and secondary headaches, and revive the discussion about the origin of these types of headaches. The application of DiI to the proximal spinosus nerve enabled the staining of all meningeal nerve fibers with all their ramifications up to the very terminals. Compared with the in vivo tracing method, this technique allows specific labeling of small regions of interest, eg, of one particular nerve.[26, 28] One disadvantage is that this type of labeling cannot
be combined with immunohistochemistry. The finding of a close relationship between the branches of the MMA and meningeal nerve fibers confirms previous classical histological[3, 5] and more recent immunohistochemical studies.[10, Idasanutlin order 12, 20] Some nerve fibers of the nerves accompanying the arterial branches terminate in or close to the adventitia, but in the majority of cases small bundles of axons and single fibers sheer out of the main nerve, divide several times dichotomously, and extend with their terminals into connective tissue. We cannot exclude that nerve fibers running with or parallel to the spinosus nerve have a sympathetic[31, 32] or parasympathetic origin click here and contribute to vascular functions.[33,
34] However, the labeled axons are probably all afferent, since the spinosus nerve arising directly from the trigeminal ganglion was labeled at its most proximal end, and there is no evidence that the tracer can cross over to neighboring axons. The myelinated fibers identified
in the electron microscopic cross-sections of the spinosus nerve are certainly trigeminal. The unmyelinated fibers running in Remak bundles are also likely to be afferent in nature because they are readily separated one from another by Schwann cell extensions (see Fig. 4E), which has been found to be a criterion for afferent fibers. The innervation this website of the cranial dura mater by the ramifying spinosus nerve was restricted to the middle cranial cavity, and spared the sagittal and transverse sinus as well as the tentorium cerebelli. This confirms earlier findings of Strassman et al, who defined two separated systems of meningeal afferent innervation: The meningeal structures surrounding the middle cranial fossa, sagittal and transverse sinus and tentorium, are supplied by a separate afferent pathway. The penetration of meningeal nerve fibers into the calvarium along sutures and emissary canals and the innervation of the cranial bone have previously been demonstrated in the mouse by histochemical preparations. Our anterograde tracings starting from the proximal spinosus nerve together with the retrograde tracings in rats, which stained somata in the trigeminal ganglion, show almost certainly that these bone penetrating fibers are of trigeminal origin.