Tracing neural connections to pain pathways with relevance to primary headaches

Background: Symptoms associated with primary headaches are linked to cranial vascular activity and to the central nervous system (CNS). Review: The central projections of sensory nerves from three cranial vessels are described in order to further understand pain mechanisms involved in primary headaches. Tracers that label small and large calibre primary afferent fibres revealed similar distributions for the central terminations of sensory nerves in the superficial temporal artery, superior sagittal sinus and middle meningeal artery. The sensory nerve fibres from the vessels pass through both the trigeminal and rostral cervical spinal nerves and terminate in the ventrolateral part of the C1-C3 dorsal horns and the caudal and interpolar divisions of the spinal trigeminal nucleus. The C-fibre terminations were located mainly in the superficial layers (Rexed laminae I and II), and the Ad-fibres terminated in the deep layers (laminae III and IV). The rostral projections from the ventrolateral C1-C2 dorsal horn revealed terminations 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 the thalamic ventral posteromedial nucleus. The terminations in the pons and midbrain were predominately bilateral, whereas those in the thalamus were confined to the contralateral side. Conclusions: The observations, done in rats with the understanding that similar trigeminovascular organization exists in man, reveal vascular projections into the brainstem and some aspects of the central regions putatively involved in the central processing of noxious craniovascular signals.