From Inside to Out: the Nerves that Pierce the Skull
Upper cervical headaches can have, in part, a distrtibution that shares a trigeminal nerve pain pattern. Chou and Lenrow (2002) identified C2 and C3 headache pain patterns as:
C2 dynatome (pain): pain ascending, 6-8 cm wide, paramedially from the subocciput to the vertex.
C3 dynatome: pain in the upper neck (<anterolateral), ear (<pinna), lateral cheek and angle of the jaw.
Typically extracranial sources of trigeminal mediated pain are thought to be from a reflex involving several nerves that eventually involve a direct branch of the trigeminal nerve. For example an upper cervical nerve causing a neurological reflex via the spinal trigeminal nucleus.
This end-stage physiological 'irritation' of the trigeminal nerve is in contrast to a direct mechanical compression that is usually associated with more pathological space occupying lesions.
More recently Schueler et al (2013 & 2014) found branches from the trigeminal nerve that innervate the dura mater and regulate bloodflow intracranially can be compressed by extracranial soft tissues. These nerves run a course originating intracranially to then traverse the cranium via the sutures and emissary canals to terminate extracranially. Extracranially these nerves innervate the connective tissue of the temporomandibular joint, periosteum and cervical muscles.
This gives the potential for soft tissues of the head and neck to not only initiate a physiological reflex response but to exert a direct compression on the trigeminal nerve.
Blake & Burnstein (2019) attributed these nerves to giving occipital pain that can radiate frontally to trigeminal innervated areas.
Innervation of the dura
Dura of the posterior cranial fossa
The dura mater covering the posterior cranial fossa is innervated by the recurrent meningeal branches of the:
Vagus nerve.
Facial nerve.
Glossopharyngeal nerve (Lee et al 2017).
Hypoglossal nerve (Lv et al 2014)
Sphenopalatine ganglion (Lv et al 2014).
Upper three cervical nerves (Lee et al 2017).
C2-3 dorsal root ganglion: Noseda et al (2019) found, in rats, neurones in the C2-3 dorsal root ganglia innervated the dura of the posterior cranial fossa.
Dura of the middle cranial fossa
The dura mater of the middle cranial fossa is innervated by all three branches of the trigeminal nerve:
Opthalamic (V1): innervates the dura the full length of the middle cranial fossa. Posterior projections of this nerve (nervus tentorii) innervates the entire region of the tentorium cerebelli and the posterior part of the falx cerebri. Anterior projections of the recurrent meningeal branches of the opthalamic nerve innervate the dura in the anterior cranial fossa (Lee et al 2017).
Maxillary (V2): recurrent meningeal branches run parallel to the proximal part of the middle meningeal artery in the dura mater innervating the dura the full length of the middle cranial fossa (Lee et al 2017).
Mandibular (V3): recurrent meningeal branches run parallel to the proximal part of the middle meningeal artery in the dura mater innervates the dura in the posterior part of the middle cranial fossa (Lee et al 2017).
Dura of the anterior cranial fossa
The dura of the anterior cranial fossa is innervated by the trigeminal nerve:
Opthalamic (V1).
Maxillary (V2).
Extracranial projections of the dural innervation
Upper cervical nerves and C2-3 dorsal root ganglion
There is a shared extracranial-intracranial innervation in the posterior cranial fossa involving the upper three cervical nerves and C2-3 dorsal root ganglion.
Schueler et al (2014) found in the nuchal region the trigeminal innervation territory to overlap considerably with that of the occipital nerves. The innervation of these pericranial muscles by collaterals of meningeal afferent fibers is substantial.
For this reason Noseda et al (2019) proposed, not only can activation of extracranial muscle nociceptors cause headaches via their intracranial branches innervating the dura but also, in reverse, activation of intracranial dural nociceptors can give rise to extracranial muscle tenderness/pain.
Recurrent meningeal branch of the trigeminal nerve (V3): spinosus nerve
The nerve that runs intracranially from the dura in the middle cranial fossa to extracranially in the periosteum and soft tissues is the spinosus nerve.
This nerve originates from: trigeminal mandibular branch (V3) --> spinosus nerve (meningeal branch). It innervates the dura in the middle cranial fossa.
Schueler et al (2014) identified this nerve as splitting into bundles. These bundles run within the dura mater along the middle meningeal artery. 10-20% of these bundles penetrate the skull through the sutures and along the emissary veins.
These authors found the nerve leaves the skull around the petrosquamos fissure to reside around the squamous suture. These bundles of nerves not only innervate the periosteum but also the insertion of the temporalis muscle.
Nerves fibers, unspecified as part of the spinosus nerve, in the posterior part of the cranial cavity also penetrate the petrosquamous fissure.
Schueler et al (2014) hypothesised two clinical points to the spinosus nerve:
This nerve has Aβâ€fibers. These fibers normally have mechanoreceptive functions. Could these nerve fibers be activated by mechanical stimuli such as sudden head movements?
These authors also hypothesised that nerve fibers running with or parallel to the spinosus nerve may have a sympathetic or parasympathetic origin that can contribute to vascular functions. Scheuler et al (2013) found noxious stimulation of the pericranial muscles (including the temporalis where fibers from the spinosus nerve terminate extracranially) causes release of CGRP intracranially. This resulted in elevated meningeal blood flow. Vasodilation of the middle meningeal artery and neurogenic inflammation of the recurrent meningeal branches from the maxillary and mandibular divisions of the trigeminal nerve in the skull base have been suggested as causes of vascular headache (Lee et al 2017).
Unspecified nerves in the anterior and posterior cranial fossa
Schueler et al (2014) found extracranial projectons from other meningeal nerves that innervate the dura mater of the anterior and posterior cranial fossae.
Nerves fibers of unspecified origin in the posterior part of the cranial fossae penetrate the petrosquamous fissure. This is along side nerve fibers from the spinosus nerve that penetrate the petrosquamous fissure having innervated the dura in the middle cranial fossa.
Embryology of the dura, cranial sutures and brain
Embryology of the dura and cranial sutures
Reviewing the intimate embryological developmental relationship of the cranial sutures and dura can throw potential light on the origin of these nerves.
Zhao and Levy (2014) postulated that these intrarcranial trigeminal afferents that cross the calvaria through the sutures and innervate the periosteum are important to the process of cranial suture closure during the early stages of cranial development.
Embryological relation of the sutures and the dura
Jin et al (2016) found a small line of the neural crest is derived from mesenchyme that remains between the two parietal bones and contributes to the signalling system that governs growth of the cranial vault at the sutures and to the development of the underlying meninges.
The mesoderm and neural crest cells don’t just form the bones of the skull but also the meningeal mesenchyme that forms all three layers of the meninges.
It does this while the sutures are developing. The growing and expanding bone fronts both invade and recruit the intervening mesenchymal tissue into the advancing edges of the bone fronts. By this action the intervening bones separate the mesenchyme into an outer ectoperiosteal layer (to become the skull) and an inner dura mater.
The outer layer of the dura forms the inner periosteum of the skull and the inner dura layer forms the dural folds (falx and tentorium).
The dura mater also expresses osteogenic growth factors that may be required for ossification of cranial vault bones.
The dura covers the brain. This dural covering has reflections acting as partitions of the cranial cavity under the calvarium, adopting a course that follows the main direction of the sutures. The folds are the falx and tentorium.
They firmly attach to the skull base at the crista galli, the cribriform plate, the lesser wings of the sphenoid and the petrous temporal crests.
The dura mater in conjunction with the falx cerebri and the tentorium cerebelli, come to define the zones where bone growth slows down and the coronal, lambdoid, and sagittal sutures develop.
Oppermann (2000) found the dura mater was not only crucial in keeping the suture a flexible fibrous joint preventing them from being obliterated by bone but it was needed to stabilise the suture. It's not until the third decade of life that the cranial vault sutures ossify and until the seventh or eighth decade of life for the facial complex.
Jin et al (2016) found these dural bands are essential in determining the shape of the brain as without them it would expand into a perfect sphere.
The expanding brain, sending signals by means of the dura mater makes the cranium grow and expand by means of expanding the cartilaginous growth plates in the cranial base and making the sutures add more bone at their periphery in the cranial vault. Gagan et al (2007) found the cells of the dura mater not only have profound influence on cell migration and differentiation in the infant skull but also the brain.
Therefore the growing brain does not actually push the bones outward. Rather, each flat bone is suspended, with the existent traction forces, within a widespread sling of the collagenous fibers of the enlarging inner (meningeal) and outter (cutaneous) periosteal layers. As these membranes grow in an ectocranial direction ahead of the expanding brain, the bones are displaced with them. This draws all of them apart, and the tensile physiological forces thus created are believed to be the stimulus that triggers the bone producing response.
Embryology of the dura and brain
These mechanical and biochemical factors aren't just related to the development of the skull but also the brain. The cells of the dura mater have a dynamic reciprocal influence on cell migration and differentiation in multiple regions of the embryonic and infant brain and skull (Gagan et al 2007)
Innervation of the intracranial vasculature
Of the autonomic nerve fibers that are strongly associated with the vascular bed, the sympathetic fibers from the SCG predominate whereas the parasympathetic fibers are less prominent (Fricke et al 2001).
Shimizu and Suzuki (2010) found the parasympathetic innervation of the dural sinuses to be:
Superior sagittal sinus: ethmoidal nerve (anterior) and tentorial nerve (posterior). Perivascular sympathetic fibers accompany the middle meningeal artery and build up a dense plexus around the sagittal sinus (Fricke et al 2001).
Inferior sagittal sinus: probably tentorial nerve.
Transverse sinus and straight sinus: tentorial nerve.
Superior petrosal sinus: tentorial nerve and V3 and fibers from the trigeminal ganglion.
Vein of Galen: tentorial nerve.
The trigeminal nerve supplies the cranial dura mater. Two separate trigeminal nociceptive systems in the cranial dura mater have been distinguished (Lee et al 2017):
V1: Posterior projections of the recurrent meningeal branches of the ophthalmic nerve (nervus tentorii) innervates the distal middle meningeal artery on the lateral convexity. The most densely innervated areas are the transverse sinus and the posterior half of the straight sinus.
References
Cervicogenic Headache (2002) Larry H. Chou and David A. Lenrow
Visualization of the tentorial innervation of human dura mater (2017). Shinâ€Hyo Lee, Kangâ€Jae Shin, Kiâ€Seok Koh, Wuâ€Chul Song
Non-Trigeminal Nociceptive Innervation of the Posterior Dura: Implications to Occipital Headache (2019). Rodrigo Noseda, Agustin Melo-Carrillo, Rony-Reuven Nir, Andrew M. Strassman and Rami Burstein
Extracranial projections of meningeal afferents and their impact on meningeal nociception and headache (2013). Schueler M, Messlinger K, Dux M, Neuhuber WL, De Col R.
Emerging evidence of occipital nerve compression in unremitting head and neck pain (2019). Pamela Blake & Rami Burstein
THE EMISSARY FORAMINA OF THE CRANIUM IN MAN AND THE ANTHROPOIDS (1930) BY G. I. BOYD
Innervation of Rat and Human Dura Mater and Pericranial Tissues in the Parietoâ€Temporal Region by Meningeal Afferents (2014). Markus Schueler, Winfried L. Neuhuber, Roberto De Col, Karl Messlinger
The trigemino-cardiac reflex: an update of the current knowledge (2009). Schaller B, Cornelius JF, Prabhakar H, Koerbel A, Gnanalingham K, Sandu N, Ottaviani G, Filis A, Buchfelder M
The sensory innervation of the calvarial periosteum is nociceptive and contributes to headache-like behaviour (2014). Jun Zhao and Dan Levy
Development and Growth of the Normal Cranial Vault : An Embryologic Review (2016). Sung-Won Jin, Ki-Bum Sim, and Sang-Dae Kim
Cranial sutures as intramembranous bone growth sites (2000). Lynne A. Opperman
Cellular dynamics and tissue interactions of the dura mater during head development (2007). Jeffrey R. Gagan, Sunil S. Tholpady, Roy C. Ogle
Innervation of the Cerebral Dura Mater (2014). Xianli Lv, Zhongxue Wu, and Youxiang Li
Headache (2010). Toshihiko Shimizu & Norihiro Suzuki
Nerve Fibers Innervating the Cranial and Spinal Meninges: Morphology of Nerve Fiber Terminals and Their Structural Integration (2001). BRITTA FRICKE, KARL HERMANN ANDRES, AND MONIKA VON DU RING
