Neuroanatomy, Spinal Trigeminal Nucleus

Structure and Function

The spinal trigeminal nucleus (SN) is located in the lateral medulla of the brainstem (see Image. Brain and Spinal Cord and Image. Brain Stem, Labels). The SN extends down to the level of the C3 vertebra, at which point it becomes continuous with the dorsal spinal horn.[1] The SN is responsible for relaying various sensory modalities, including temperature, touch, and pain from the ipsilateral portion of the face, as well as nociceptive inputs from the supratentorial dura mater.[2]

The SN incorporates sensory information from different cranial nerves, but its inputs and physiological importance come principally from the three extracranial divisions of the trigeminal nerve (V1, ophthalmic; V2, maxillary; V3, mandibular). These extracranial nerves initially fuse at the trigeminal ganglion, entering the cranial vault through the superior orbital fissure, foramen rotundum, and foramen ovale.[3] After the trigeminal ganglion, the fibers divide into sensory and motor rootlets, which are then distributed to the trigeminal nuclei (mesencephalic nucleus, motor nucleus, principal sensory nucleus, and spinal nucleus) before projecting onwards to the cortex.[4]

The spinal nucleus of the trigeminal nerve is a longitudinally-shaped nucleus situated in the caudal pons and medulla, which receives sensory afferents relating to pain and temperature from the orofacial region supplied by the trigeminal nerve and, together with the principal sensory nucleus, is sometimes termed the trigeminal sensory nuclear complex (TSNC).[1] The SN also receives afferent fibers from other cranial nerves, including the facial nerve (CN VII) via the geniculate ganglion, the glossopharyngeal nerve (CN IX) via the petrosal ganglion, and the vagus nerve (CN X) via the nodose ganglion.[5]

The spinal trigeminal nucleus is further subdivided anatomically into the pars oralis, pars interporalis, and pars caudalis.[6] The pars oralis is the termination of afferent connections from the oral and nasal regions and contains circuits involved in brain stem reflexes. The pars interpolaris receives inputs from the ipsilateral face and forms the ascending anterior trigeminothalamic tract with the pars oralis. The pars caudalis also receives input from the face, forehead, cheek, and jaw, as well as being involved in transmitting temperature sensation from this area. The topographical representation of the inputs to the spinal trigeminal nucleus is inverted, such that the area encoding the forehead is represented ventrally (distally), and the area encoding the oral region is represented dorsally (proximally). The SN projects both contralaterally and ipsilaterally to the ventral posteromedial nucleus of the thalamus via the ventral and dorsal trigeminothalamic tracts.[1] This sensory information is relayed from the thalamus to the primary motor cortex via the primary sensory cortex, allowing response to stimuli of the face. This ability to react to noxious stimuli of the face and remove ourselves from harm makes the spinal trigeminal nucleus a pivotal component of the sensory pathway.

Embryology

During embryological development, the cranial nerve nuclei are some of the earliest structures in the brain to emerge and are distinguishable by day 28. The trigeminal sensory nuclei develop from neural crest cells, a highly migratory population of multipotent cells that originates in the dorsal neural tube (see Diagram. Neural Crest Derivatives.)[7] The trigeminal nuclei develop initially in the metencephalon and myelencephalon before being partly displaced into the mesencephalon.[8]

Blood Supply and Lymphatics

The area of the brainstem where the spinal trigeminal nucleus is situated is supplied by the posterior inferior cerebellar artery (PICA).[9] The PICA is the four branches from the paired vertebral arteries and arises approximately 16 mm before the vertebral arteries join to form the basilar artery.[10] This is further divided into 5 anatomical segments: the anterior medullary segment, lateral medullary segment, tonsillomedullary segment, telovelotonsillar segment, and cortical segment.[11] Specifically related to the spinal nucleus of the trigeminal nerve are the first and second of these segments, which pass over the ventrolateral part of the brainstem. Any disruption of blood flow through the vertebral artery or posterior inferior cerebellar artery would interrupt the processing of sensory information from the trigeminal nerve. Such pathologies include vertebral artery dissection, thrombotic occlusion, and stenosis from extrinsic compression, such as from a tumor or fibrous band.[12]

Nerves

The spinal trigeminal nucleus incorporates sensory information from all three branches of the trigeminal nerve (CN V). CN V1, also known as the ophthalmic nerve, relays sensory information from the face in regions located above the orbit of the eyes. CN V2, also known as the maxillary nerve, is primarily responsible for sensory information between the orbit and the mouth. The final branch is CN V3, also known as the mandibular nerve. CN V3 has both a sensory component as well as a motor component; however, only the sensory component projects to the SN. The spinal trigeminal nucleus also consolidates sensory input from the facial, glossopharyngeal, and vagus nerves; this is a minor role of SN in comparison to its integration of sensory information from the three branches of the trigeminal nerve.

Surgical Considerations

Because the spinal trigeminal tract extends inferiorly down to the level of C3, this tract can be involved clinically in patients with craniovertebral junction pathologies. For the same reason, surgical intervention at this level, for example, posterior fossa decompression, could affect this area and related brainstem structures. The caudal end of the spinal trigeminal nucleus terminates at the obex of the fourth ventricle in a raised tubercle, termed the trigeminal tubercle. This is a valuable landmark for neurosurgeons operating in this region.

Clinical Significance

Lateral Medullary Syndrome

Lateral medullary syndrome, also known as medullary or posterior inferior cerebellar artery syndrome, occurs due to the occlusion of the posterior inferior cerebellar artery or the vertebral artery. An occlusion to either of these arteries can result in a lack of blood flow to the lateral medulla, the location of the spinal trigeminal nucleus. The primary ischemic events that trigger lateral medullary syndrome can result from stenotic blood vessels, as seen in adults, often with other comorbid conditions. In children, however, ischemia can be due to injury to the vertebral artery following a hyperextension neck injury.[13] 

The lateral medullary syndrome presents with many symptoms, including contralateral loss of pain and temperature sensation in the body with ipsilateral Horner syndrome, dysphagia, and loss of sensation in the face.[14] This ipsilateral loss of facial sensation is due to a lack of blood supply via the posterior inferior cerebellar artery to the spinal trigeminal nucleus. This nucleus is responsible for relaying sensory information from the trigeminal nerve to the primary sensory cortex, making it a key player in the presentation of lateral medullary syndrome.

Trigeminal Neuralgia

Trigeminal neuralgia is a condition that most often presents with unilateral, stabbing, and paroxysmal painful sensations from the face along the trigeminal nerve distribution.[15] There are myriad theories regarding the underlying mechanism of this condition. The etiologies have been broken down into idiopathic, primary, and secondary trigeminal neuralgia. Suggested peripheral mechanisms involve defects along the trigeminal nerve pathway before entering the brainstem. A recent hypothesis attributes the pain of trigeminal neuralgia to a central mechanism involving the pars oralis of the spinal trigeminal nucleus.[16] 

This theory has as its basis the characterization of trigeminal neuralgia as focal epileptic and neuronal hyperactivity. An increase in activity at the spinal trigeminal nucleus has been shown to precipitate the pain seen in trigeminal neuralgia in both cats and monkeys. Furthermore, the administration of anti-epileptic medications in cats and monkeys was able to decrease the intensity and duration of the attacks. The difficulty of treatment approaches makes the understanding of trigeminal neuralgia imperative. Though there is no consensus on the underlying mechanism of trigeminal neuralgia, recent evidence suggests that the spinal trigeminal nucleus, particularly the pars oralis, plays a vital role in this process.[17]

Chronic Orofacial Pain 

Understanding chronic orofacial pain is important as it has been determined as a source of significant psychological distress in patients. This distress is likely because procedures and medications often cannot relieve symptoms.[18] A better understanding of the underlying mechanism may help create new solutions to this lack of treatment efficacy. In processing orofacial pain, the spinal trigeminal nucleus, specifically the pars caudalis, projects to the ventral posteromedial thalamic nucleus and the parabrachial nucleus.[19] 

A recent study was conducted in humans to demonstrate changes in synapses of patients with chronic orofacial neuropathic pain. Utilizing T1-weighted MRI imaging, the study showed that alterations in the anatomy of primary synapses of the trigeminal nerve, particularly in the pars oralis, are critical for both the generation and maintenance of chronic pain in the distribution of the trigeminal nerve. These changes included significant regional gray matter volume reduction, a decrease in mean diffusivity, and a fractional anisotropy increase.[20] Imaging of the peripheral pathways of the trigeminal nerve showed no significant change in the anatomy in the setting of chronic orofacial pain, thus decreasing the likelihood of its involvement in the pathophysiology of this condition. Anatomical changes to the pars oralis of the spinal trigeminal nerve are responsible for the presentation of chronic orofacial pain. 

Craniocervical Dystonia

Craniocervical dystonia is a poorly understood neurological disorder, part of the group of primary focal dystonias that present with involuntary muscle contractions, sustained or intermittent.[21] No cause or candidate pathological gene has been found, and treatment for this condition, which has significant deleterious effects on quality of life, remains limited.[22] Trigeminal reflexes, which indicate the functioning pathway of the trigeminal nerve and nuclei (and therefore the SN), include head retraction, corneal reflex, and jaw jerk reflexes.[23] 

The observation that these reflexes associated with the trigeminal ganglia are aberrant in patients with craniocervical dystonia has led to the hypothesis that aberrant plasticity in the basal ganglia leading to tonic inhibition of the trigeminal sensory complex may be involved in the pathological process of this condition.[24] Furthermore, anatomical and electrophysiological experimental evidence has demonstrated the need for the normal function of the trigeminal sensory complex for normal motor control of head and neck muscles.[6] For these reasons, it is hypothesized that neuromodulation of this area, including the trigeminal spinal nucleus, either by invasive or non-invasive means, may provide therapeutic benefits in patients with this condition.[6]

Other Issues

There is evidence in rats suggesting the presence of oxytocin receptors in both the medulla oblongata and pons.[25] These oxytocin receptors are present in the spinal trigeminal nucleus; however, as is seen with oxytocin receptors in other regions of the medulla and pons, they disappear by postnatal day 10. At the time of birth, there is an increase in the maternal release of oxytocin, likely acting on these oxytocin receptors as well; this indicates an early and transient role of oxytocin in the neuronal development of the neonatal period. The full extent of the effect of oxytocin on neuronal development postnatally is yet to be determined.