Clinical Examination of the Cranial Nerves

Adam Fisch , in Nerves and Nerve Injuries, 2015

Spinal Trigeminal Nucleus Somatotopy and Projections

The spinal trigeminal nucleus runs medial to the spinal trigeminal tract, has an onionskin somatotopy, and divides into three different cytoarchitectural regions. Within the spinal trigeminal nucleus, pars oralis is the superior-most subnucleus: it spans from the pons to the mid-medulla; pars interpolaris is the middle subnucleus: it lies in the mid-medulla; and pars caudalis is the inferior-most subnucleus: it spans from the lower medulla to the upper cervical spinal cord (variably listed termination is anywhere from C2 to C4). The somatotopic features of the face in the spinal trigeminal somatotopic map are stretched and distorted to fit into the proportions of the long, columnar spinal trigeminal pars caudalis subnucleus (imagine pulling a rubber mask off of your face to visualize the distortion)—the most superior area is the inferior medulla and the most inferior area is the upper cervical spinal cord. The superior features of the face (e.g., the eyes) lie anterior and the inferior features (e.g., the jaw) lie posterior; the most superior portion of the pars caudalis subnucleus receives the lips and perioral area and the most inferior component receives the outer ears. Note that whereas the majority of spinal trigeminal nuclear innervation comes from the fifth cranial nerve, additional, minor input comes from cranial nerves VII, IX, and X ( Figure 15.14).

Figure 15.14. Cranial Nerve V: Tracts.

 Reproduced with permission from Fisch, A. Neuroanatomy: Draw it to Know it, 2nd ed. (Oxford University Press, 2012), Drawing 13–3, pg 219.

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The Somatosensory System II

S. Warren , ... N.F. Capra , in Fundamental Neuroscience for Basic and Clinical Applications (Fifth Edition), 2018

Central Pathways from the Face and Oral Cavity

The spinal trigeminal nucleus, located medial to the spinal tract, is the site of termination for fibers of the spinal trigeminal tract (Figs. 18.17 and 18.18). On the basis of cytoarchitecture, this nucleus is divided into a pars caudalis, a pars interpolaris, and a pars oralis. The caudal subnucleus (pars caudalis) (Figs. 18.15 and 18.16) extends from C2 or C3 rostrally to the level of the obex. This part of the spinal nucleus shares many cytoarchitectural similarities with the posterior horn. For this reason, it has been termed the medullary posterior horn and has been divided into layers that correspond to Rexed spinal cord laminae (Fig 18.7). The substantia gelatinosa is largely continuous with lamina II of the spinal cord, and the magnocellular region is continuous with laminae III and IV. The pars caudalis and the posterior horn also show homology in the distribution of neurotransmitters. For example, substance P and calcitonin gene–related peptide are localized in nociceptive C fibers that terminate in both of these areas.

The pars caudalis plays an important role in the transmission of nondiscriminative touch, nociceptive, and thermal sensations from the face and oral cavity. This role is reflected by the fact that central processes of Aδ and C fibers terminate somatotopically in this subnucleus. In addition to the somatotopy within the pars caudalis, an onion-skin pattern (also called onion-peel sensory loss) of facial pain representation is oriented along the rostrocaudal axis of the subnucleus (Figs. 18.15B and 18.16). The nociceptive fibers that innervate circumoral and intraoral zones (teeth, gums, and lips) terminate rostrally, close to the obex at the interface of the pars interpolaris and the pars caudalis. Fibers innervating progressively more caudal and lateral regions of the face terminate in progressively more caudal regions of the spinal trigeminal nucleus, pars caudalis (Fig. 18.16). Many second-order neurons in the subnucleus caudalis receive convergent input from small-diameter fibers that innervate cutaneous and deep tissues (jaw muscles and the temporomandibular joint). Convergence of information from different regions is thought to contribute to the referral of pain and may be involved in the manifestation of less well understood clinical problems such as temporomandibular joint disorders and atypical facial pain.

At medullary levels, the posterior inferior cerebellar artery supplies the territory of the ALS fibers as well as the spinal trigeminal nucleus and tract (Figs. 18.10 and 18.17). Vascular lesions involving this vessel produce characteristic sensory symptoms collectively known as the lateral medullary (Wallenberg) syndrome or the posterior inferior cerebellar artery syndrome. The sensory symptoms of this syndrome may include a contralateral loss of pain (hemianalgesia) and temperature (hemithermoanesthesia) sensibility over the body and ipsilateral loss of these modalities over the face. However, the extent of damage after posterior inferior cerebellar artery lesions shows remarkable variation, and the combination of symptoms is representative of the structures served by this artery (Fig. 18.19).

The interpolar subnucleus (pars interpolaris) is located between the level of the obex and the rostral pole of the hypoglossal (XII) nucleus. The most rostral subdivision is the oral subnucleus (pars oralis), which extends from the level of the rostral pole of the hypoglossal nucleus to the caudal end of the trigeminal motor nucleus (Figs. 18.15 and 18.17). Some neurons in the pars interpolaris and the pars oralis contribute to ascending somatosensory pathways, whereas others project to the cerebellum. In addition to projection neurons, the spinal trigeminal nucleus, particularly the subnucleus oralis, contains many local circuit neurons involved in brainstem reflexes.

The axons of second-order trigeminothalamic neurons in the spinal trigeminal nucleus decussate, then coalesce to form the anterior trigeminothalamic tract, and ascend through the brainstem just posterior to the medial lemniscus (Figs. 18.17 and 18.18). These fibers terminate in the ventral posteromedial (VPM), the posterior, and the intralaminar nuclei of the thalamus. As noted in Chapter 17, this pathway also carries crossed fibers from the principal trigeminal nucleus. The principal nucleus fibers terminate in the core of VPM, whereas spinal nucleus fibers terminate in its periphery. At the pontomesencephalic junction, anterior trigeminothalamic fibers are adjacent to ALS fibers at the lateral margin of the medial lemniscus (Figs. 18.10 and 18.14). Like ALS fibers, ascending anterior trigeminothalamic axons terminate in or give rise to collaterals that supply the reticular formation.

A particularly prominent target of some of these collaterals is the parabrachial nuclear complex. Located adjacent to the superior cerebellar peduncle (brachium conjunctivum), the parabrachial nuclei serve as an important relay for spinal and trigeminal pain fibers as well as for ascending axons carrying visceral sensory information. In addition to regulating oral and facial reflexes, projections from the reticular formation terminate in the dorsal thalamus in the intralaminar nuclei and the medial region of the posterior nucleus. The intralaminar nuclei project widely to the striatum and cortex, especially the frontal and somatosensory cortex. The medial region of the posterior nucleus projects to the head representation in the secondary somatosensory cortex.

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Trigeminal Sensory System

PHIL M.E. WAITE , KEN W.S. ASHWELL , in The Human Nervous System (Second Edition), 2004

Spinal Trigeminal Nucleus Caudalis

The spinal trigeminal nucleus caudalis extends from the obex for approximately 15 mm to the C 2 level (Fig. 29.3), where it becomes continuous with the dorsal horn. Its similar laminar organization to the spinal dorsal horn (Chapter 7) has led to its alternative name, the medullary dorsal horn (Gobel et al., 1981). Thus Sp5C contains a marginal zone (subnucleus zonalis, lamina 1), a substantia gelatinosa resembling Rexed's lamina 2, and a magnocellular layer, equivalent to nucleus proprius (lamina 3 and 4) of the dorsal horn (Fig. 29.3). In addition, some authors recognize a deeper zone corresponding to laminae 5 and 6.

The marginal zone in human tissue consists of a thin sheet of cells containing large multipolar neurones, some over 60 μ m in diameter (Usunoff et al., 1997) with small and medium-sized neurones also present. In rat, cat, and monkey, fusiform, pyramidal, and multipolar cells are described (Gobel, 1978; Zhang et al., 1996; Yu et al., 1999), with different functional properties for each (see later). Inputs to the marginal zone arise mainly from small-diameter myelinated fibers as well as unmyelinated afferents from all cranial tissues (reviewed Craig, 1996).

The human substantia gelatinosa was rather aptly described by Olszewski (1950) as horseshoe-shaped in cross section (Fig. 29.3) and consists of relatively densely packed small, oval, or fusiform cells (10–20 μ m in diameter). This layer reacts strongly for AChE and is rich in neuropeptides such as substance P, CGRP, cholecystokinin, and somatostatin (Inagaki et al., 1986; Clements and Beitz, 1987; Carpentier et al., 1996). This region also contains the NGF receptor, trkA, which is especially dense in pre and perinatal human tissue, but is also present in adults (Quartu et al., 1996). The region is rich in GABAergic somata and fibers (rat, Haring et al., 1990; Ginestal and Matute, 1993). It receives predominantly small-diameter myelinated and unmyelinated afferents. Synaptic glomeruli, in which glutamatergic primary afferents are both pre- and postsynaptic to GABAergic terminals, have been described (rat, Clements and Beitz, 1987; cat, Iliakis et al., 1996).

The magnocellular zone has medium-sized diameter (25 μm) oval or fusiform cells with scattered small and large neurones. In the rat, many cells here contain glutamate, and some of these project to VPM (Magnussen et al., 1986, 1987). Synaptic glomeruli are present, often with scalloped glutamatergic profiles (Clements and Beitz, 1991). The magnocellular zone has a moderate level of AChE reactivity.

Low-threshold mechanical responses, high threshold nociceptive specific responses, thermosensitive specific (COLD) responses, HPC (heat, pinch, cold) cells, and wide dynamic range (WDR) neurones are all present in Sp5C (cat, Hu, 1990; monkey, Dostrovsky and Craig, 1996; reviewed Sessle, 2000). Low-threshold mechanical responses are found predominantly in the magnocellular zone along with some thermal specific units (monkey, Price et al., 1976). In contrast, the marginal zone contains nociceptive specific, COLD, HPC, and WDR responses (monkey, Price et al., 1976; Bushell et al., 1984; reviewed Sessle, 2000, and see later section on trigeminal nociception). Intracellular recordings from lamina 1 cells in cat spinal cord suggest that there is a structure/function correlation: fusiform and pyramidal cells correspond to nociceptive specific and COLD responses, respectively, whereas most multipolar cells showed HPC responsiveness (Han et al., 1998). In monkey spinal cord, the fusiform and multipolar cells express the substance P receptor (neurokinin-1) supporting their role in nociception (Yu et al., 1999). The role of trigeminal marginal zone neurons in nociception and thermal discrimination has been indicated by recordings in awake monkeys (Dubner et al., 1981; Hayes et al., 1981; Bushnell et al., 1984). The responses of COLD cells depended on the behavioral significance of the stimuli, suggesting the involvement of these cells in sensory discrimination, rather than merely reflex activation.

Projections of Sp5C are extensive. Lamina 1 cells project to several thalamic regions including VPM, Po, and the midline and intralaminar nuclei (primate, Ganchrow, 1978; cat and monkey, Burton and Craig, 1979; cat, Shigenaga et al., 1983; rat, Shigenaga et al., 1979; Yoshida et al., 1991; Iwata et al., 1992; and see Chapter 30, Fig. 30.8B) as well as a new nucleus described by Blomqvist et al. (2000) as the posterior part of the ventral medial nucleus (VMpo, referred to as basalis nodalis in Chapter 20). Laminar 1 also gives both direct hypothalamic projections (rats, Malick and Burstein, 1998) and indirect projections through the parabrachial area (Slugg and Light, 1994; Jasmin et al., 1997). The substantia gelatinosa projections are predominantly local, to the adjacent magnocellular zone and reticular formation (primate, Tiwari and King, 1974). The magnocellular zone projects to VPM, zona incerta, the facial nucleus, trigeminal motor nucleus, and adjacent reticular formation as well as ipsilateral spinal cord (Iwata et al., 1992; Carpentier et al., 1981). Magnocellular cells also project to more rostral trigeminal nuclei, Sp5O and Sp5I (primate, Tiwari and King, 1974; Price et al., 1976; cat, Hu and Sessle, 1979; rat, Hallas and Jacquin, 1990). These intranuclear connections are likely to modulate activity in these rostral regions.

An interesting recent study has reported a discrete thermospecific region in lamina 1 in the owl monkey (Craig et al., 1999). Cells here responded to cold stimuli (COLD cells) with small receptive fields on nasal and labial regions and had a pyramidal morphology similar to thermal cells in cats and rats. These cells project to the posterior ventromedial nucleus (VMpo), identified as a thermal and nociceptive region in monkey and human thalamus (Craig et al., 1994, and referred to as basalis nodalis, in Chapter 20 and see later). This region of lamina 1 and the associated pathway was suggested to provide specialized thermosensitivity, likely to be relevant the nocturnal navigation and foraging behavior of the owl monkey Craig et al. (1999).

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Reticular Formation

Anja K.E. Horn , Christopher Adamczyk , in The Human Nervous System (Third Edition), 2012

Clinical Aspects

Lesions involving the spinal trigeminal nucleus at the interpolaris/caudalis border and the adjacent reticular formation disrupt corneal reflex blinks in human. In Parkinson disease, the blink rate is increased, presumably due to an increased excitability of the facial motoneurons. The following hypothesis is suggested: the dopamine deficit in the substantia nigra results in an increased inhibition of the superior colliculus by the GABAergic projections from the substantia nigra pars reticulata. This results in a reduced excitation of the raphe magnus from the superior colliculus leading to a reduced inhibition of the spinal trigeminal nucleus from the serotoninergic neurons of the raphe nuclei, which produces in an insed excitability of the trigeminally evoked blink reflex ( Basso et al., 1996a, 1996b; for review see Sibony and Evinger, 1998).

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Organization of Human Brain Stem Nuclei

YURI KOUTCHEROV , ... GEORGE PAXINOS , in The Human Nervous System (Second Edition), 2004

Spinal Trigeminal Nucleus

The caudal spinal trigeminal nucleus (Sp5) is characterized by strong AChE reactivity in the superficial layers, including the substantia gelatinosa ( Figs. 10.1 and 10.2). The marginal zone of the caudal part of Sp5 can be distinguished because it is less AChE reactive than the gelatinous nucleus but more than the spinal tract. Some AChE-reactive cells are found totally within the cuneate fasciculus, yet strong AChE reactivity suggests that they most likely belong to the gelatinous part of the caudal Sp5 rather then to the cuneate system. Also, a recent study revealed NPY mRNA expression within the nucleus (Pau et al., 1998).

The oral Sp5 (Sp5O) has a concentric pattern of AChE reactivity with an extremely AChE dense core (Figs. 10.10 and 10.11). It is succeeded rostrally by the less reactive principal sensory nucleus of the trigeminal nerve. In the principal sensory trigeminal nucleus the AChE reactivity is distributed in small patches adulterated by negative areas.

In the principal sensory trigeminal nucleus the AChE reactivity is distributed in small patches adulterated by negative areas. The interpolar nucleus (Sp5I) (Figs. 10.3–10.9) displays moderate AChE reactivity, although there are occasional extremely intense patches that correspond to parvicellular regions. In the ventral part of the nucleus a rodlike structure appears (circular in cross-section), featuring small compact neurones and extremely AChE-dense neuropil. No such structure appears in the rat. Both Sp5O and Sp5I are reported to contain significant number of somatostatin receptors as revealed by somatostatin binding sites (Carpentier et al., 1996).

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Organization of Brainstem Nuclei

George Paxinos , ... Charles Watson , in The Human Nervous System (Third Edition), 2012

Spinal Trigeminal Nucleus

The caudal spinal trigeminal nucleus (Sp5) is characterized by strong AChE reactivity in the superficial layers, including the substantia gelatinosa. The marginal zone of the caudal part of Sp5 can be distinguished because it is less AchE-reactive than the gelatinous nucleus but more than the spinal tract. Some AChE-reactive cells are found totally within the cuneate fasciculus, yet strong AChE reactivity suggests that they most likely belong to the gelatinous part of the caudal Sp5 rather then to the cuneate system. Also, NPY mRNA expression was found within this nucleus ( Pau et al., 1998).

The oral Sp5 (Sp5O) has a concentric pattern of AChE reactivity with an extremely AChE dense core (Figures 8.31–8.35). It is succeeded rostrally by the less reactive principal sensory nucleus of the trigeminal nerve. In the principal sensory trigeminal nucleus the AChE reactivity is distributed in small patches adulterated by negative areas. In the principal sensory trigeminal nucleus the AChE reactivity is distributed in small patches adulterated by negative areas. The interpolar nucleus (Sp5I) displays moderate AChE reactivity, although there are occasional extremely intense patches that correspond to parvicellular regions (Figures 8.16–8.30). In the ventral part of the nucleus a rodlike structure appears (circular in cross-section), featuring small compact neurons and extremely AChE-dense neuropil. No such structure appears in the rat. Both Sp5O and Sp5I are reported to contain significant numbers of somatostatin receptors as revealed by somatostatin-binding sites (Carpentier et al., 1996). In humans, Sp5 neurons have been shown to contain serotonin, calcitonin gene-related peptide, and substance P (Smith et al., 2002), bombesin (Lynn et al., 1996), glial cell line-derived neurotrophic factor (GDNF) (Del Fiacco et al., 2002), met-enkephalin (Covenas et al., 2004), neurokinin (Covenas et al., 2003), and parathyroid hormone receptor 2 (PTH2R) (Bago et al., 2009) immunoreactivities.

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Cerebellum

Roy V. Sillitoe , ... Charles Watson , in The Mouse Nervous System, 2012

Hindbrain Trigeminal Nuclei

The principal trigeminal nucleus and the interpolar spinal trigeminal nucleus send afferents to the orofacial recipient areas of cerebellar cortex in the rat ( Watson and Switzer, 1978). The major orofacial recipient areas in the cerebellum are Crus 1, Crus 2, the paramedian lobule, and the uvula of the vermis (Falls et al., 1985). In the mouse, the ipsilateral principal nucleus and the interpolar spinal nucleus are the two major sources of trigeminal afferents to the cerebellum; there are minor projections from other parts of the hindbrain trigeminal complex (caudal spinal, dorsomedial spinal, trigeminal transition zone, and the trigeminal-solitary transition zone.

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Ascending and Descending Pathways in the Spinal Cord

David Tracey , in The Rat Nervous System (Third Edition), 2004

Trigeminal and Dorsal Column Nuclei

Neurons in all three subnuclei of the spinal trigeminal nucleus (Sp5C, Sp5I, and Sp5O) send axons as far as the thoracic cord ( Lakke, 1997) or further (Ruggiero et al., 1981). Trigeminospinal neurons are also found in the principal sensory nucleus (Phelan and Falls, 1991) and the mesencephalic trigeminal nucleus (Leong et al., 1984).

Descending projections from the gracile and cuneate nuclei are present in the rat (Burton and Loewy, 1977; Villanueva et al., 1995); there is also a spinal projection from the external cuneate nucleus (Leong et al., 1984; Zemlan et al., 1979). The gracile nucleus seems to project to the lumbar cord and sacral cord, while neurons in the cuneate nucleus project mainly to the cervical cord (laminae 1,4& 5). Cuneospinal neurons are concentrated in the ventral parts of the nucleus (Leong et al., 1984; Masson et al., 1991).

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The Nervous Systems of Early Mammals and Their Evolution

C. Watson , ... L. Puelles , in Evolution of Nervous Systems (Second Edition), 2017

2.02.4.9 Plurisegmental Nuclei

A number of hindbrain nuclei, notably the spinal trigeminal and vestibular nuclei, extend as longitudinal columns across a number of rhombomeres. Because embryonic rhombomeric boundaries become invisible as development proceeds, these nuclei appear at first to contradict the significance of a neuromeric organization of the hindbrain, and these longitudinal formations gave rise to the concept of brain columns [ie, the origin of the columnar model of Herrick (1910)]. The columnar model at first appears to be opposed to the neuromeric model, but is actually complementary to it. Fate mapping has shown that the rhombomeric structural blocks simply become hidden and continue to exist (Wingate and Lumsden, 1996; Marin and Puelles, 1995; Cambronero and Puelles, 2000). It has been predicted and confirmed that the unique molecular identities and consequent differential hodological or functional properties of individual segments will persist (eg, Diaz and Glover, 2002; Diaz et al., 2003; Diaz and Puelles, 2003; Straka et al., 2006; Tomás-Roca et al., 2016).

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Update on Emerging Treatments for Migraine

Shu-Ting Chen , Jr-Wei Wu , in Progress in Brain Research, 2020

6.4 Expression in the central nervous system

Some CGRP fibers originating in the trigeminal ganglion terminate in the spinal trigeminal nucleus and laminae I & II of the dorsal horn of the upper cervical spinal cord (C1-C2) ( Sugimoto et al., 1997) and CGRP fibers are located in the superficial laminae of the spinal trigeminal nucleus (Eftekhari et al., 2013; Liu et al., 2003, 2004; Sugimoto et al., 1997). Using biotinylated dextran amine (BDA) labeling, researchers found ventrolateral dorsal horn of segments C1 and C2 project to several nuclei in the pons and midbrain (Liu et al., 2009). Pain signals rely on second-order neurons to transmit messages to the brainstem and other central structures (Akerman et al., 2011). As in the periphery, the central CGRP positive fibers are thin and unmyelinated, while CGRP receptors are localized in thicker Aδ-fibers (Russell et al., 2014).

CGRP and CGRP receptors are widely distributed in the central nervous system. CGRP-containing cell bodies have been found in the hypothalamus, lateral hypothalamus, amygdala, hippocampus, ventromedial nucleus and the geniculate body of the thalamus, and premammillary nucleus (Hokfelt et al., 1992), while CGRP-containing fibers are found in the anterior pituitary gland (Gulbenkian et al., 2001). CGRP receptors are expressed in the thalamus, hypothalamus, amygdala, cortex, and brainstem (Eftekhari et al., 2013; Warfvinge and Edvinsson, 2019). All of these regions expressing CGRP and CGRP receptors are linked to pain modulation and associated symptoms of migraine, including photophobia, phonophobia, and nausea (Goadsby et al., 2017a).

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