Central projections of sensory innervation of cranial vessels

Abstract: Primary headaches (e.g. migraine and cluster headache), the symptoms of which is associated with cranial vascular activity, is likely to be dependent on a primary central nervous system dysfunction. To further our understanding of the mechanisms behind primary headaches, we investigated the central projections of sensory nerves from three cranial vessels by tract-tracing techniques. In papers I-III, we examined the central terminations of sensory nerves in the superficial temporal artery, the superior sagittal sinus and the middle meningeal artery. Wheat germ agglutinin conjugated horseradish peroxidase (WGA-HRP) and cholera toxin subunit b (CTb) were used as transganglionic tracers in separate experiments to label both the small and large caliber primary afferent fibers. The distributions of labeled central terminations were closely similar for the nerves in all three vessels. The sensory nerve fibers from the vessels passed through both the trigeminal and the rostral cervical spinal nerves. They terminated in the ventrolateral part of C1-C3 dorsal horn and the caudal and interpolar divisions of the spinal trigeminal nucleus, with a focus extending from the C2 dorsal horn into the caudal spinal trigeminal nucleus. The WGA-HRP labeled terminations mainly located in the superficial layers (laminae I and II) while the CTb labeled fibers terminated in the deep layers (laminae III and IV). The WGA-HRP and CTb-labeled terminations together formed a wedge-shaped column extending through laminae I-IV ventrolaterally in the C1-C3 dorsal horn. In paper IV, we examined the rostral projections from the ventrolateral C1-C2 dorsal horn by iontophoretic injections of the anterograde tracer biotinylated dextran amine (BDA). Following BDA injections into laminae I-II, labeled terminations were seen, among others, in the medial and lateral parabrachial nuclei, the cuneiform nucleus, the periaqueductal gray, the deep mesencephalic nucleus, the thalamic posterior nuclear group and its triangular part, and in the thalamic ventral posteromedial nucleus. The terminations in the pons and the midbrain were predominately bilateral, whereas those in the thalamus were confined to the contralateral side. Following injections into laminae I-IV, anterograde labeling was more extensive in the above nuclei and also evident in other areas. The regions labeled following laminae I-II injections may be involved in the central processing of noxious signals of craniovascular origin and therefore putatively involved in mechanisms associated with primary headaches.