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14 Articles in Volume 12, Issue #8
Board-certified Doctor Cleared of Criminal Charges for High-dose Opioid Prescribing
John F. Kennedy's Pain Story: From Autoimmune Disease To Centralized Pain
Key Clinical Pearls for Treating Headache Patients
Lest We Forget Pain Treatment Is a Stepladder Approach
Mathematical Model For Methadone Conversion Examined
Pain Management Coding Changes Can Sting, But Knowledge Can Help Ease the Pain
Pain Treatment—Then and Now
Platelet Rich Plasma Prolotherapy For Rotator Cuff Tears: Case Challenge
September 2012 Letters to the Editor
September 2012 Pain Research Updates
The Sports Injury-Pain Interface: Highlights from the American Orthopaedic Society for Sports Medicine Annual Meeting
Trigeminal Neuralgia: A Closer Look at This Enigmatic and Debilitating Disease
What Every Physician Should Know About Non-pharmaceutical Pediatric Pain Care
When Referring Patients, Not All Pain Specialists Are the Same

Trigeminal Neuralgia: A Closer Look at This Enigmatic and Debilitating Disease

Part one of this two-part series discusses the etiology and differential diagnosis of trigeminal neuralgia. Part two will discuss pharmaceutical and surgical treatment options.

Trigeminal neuralgia (TN), also known as tic douloureux, is a relatively common neuropathic disorder that is characterized by sudden severe episodes of lancinating or electric pain along the distribution of cranial nerve V (CNV). With an annual incidence of approximately 4.7 per 100,000 people, TN remains one of the most frequent causes of facial pain worldwide.1 Despite its prevalence, there is not a precise description of its etiology or pathogenesis. Occurring slightly more often in women, TN appears more commonly after the fifth decade of life, although some cases have been reported in childhood. With regards to risk factors, hypertension seems to have a tenuous association with TN. People suffering from this condition have been known to acquire anxiety disorders due to the continual fear of an episode; depression has also been documented in a fair number of people who persistently suffer from TN. These devastating effects as well as the intense periods of pain that trademark this disorder have allowed it to earn the title of the “suicide disease.”

Cranial Nerve V
The trigeminal nerve is composed of three divisions that innervate distinct regions of the face: the ophthalmic nerve (V1), the maxillary nerve (V2), and the mandibular nerve (V3). Each division originates from the trigeminal ganglion, or gasserian ganglion, which emerges on the lateral portion of the pons bilaterally.2 After departing from the pons, each division disperses to their particular facial dermatomes (Figure 1).

The ophthalmic nerve (V1) gives off three main branches (the frontal nerve, nasociliary nerve, and lacrimal nerve), which innervate areas of the face that extend from the vertex of the scalp to the apex of the nose. The frontal nerve is considered the largest branch of the ophthalmic nerve and it separates into the supra-orbital and supra-trochlear nerves, which supply a large portion of the scalp and anteromedial forehead, respectively.The nasociliary nerve branches off into the infra-trochlear nerve as well as the anterior and posterior ethmoidal nerves. The anterior ethmoidal nerve is notable because its terminal branch, the external nasal nerve, innervates the nasal vestibule. The smallest branch of the ophthalmic nerve is the lacrimal nerve, whose distribution includes the lateral aspect of the eyelids. The lacrimal nerve also participates in the parasympathetic innervation to the lacrimal glands.3

The maxillary nerve (V2) is a purely sensory nerve that emerges from the cranium through the foramen rotundum to innervate the maxillary region of the face and the skin along the zygomatic arch.The maxillary nerve also carries parasympathetic fibers from cranial nerve seven to innervate the mucous glands of the palate, maxillary sinus, and nasal cavity. The major branches of the maxillary nerve include the infra-orbital, zygomaticofacial, and zygomaticotemporal nerves.

The mandibular nerve (V3) is the only branch of the trifurcation of cranial nerve five that serves both motor and sensory functions. It breaks off into four major branches including the auriculotemporal, buccal, lingual, and inferior alveolar nerves. The auriculotemporal nerve is unique in that it is in close proximity to the middle meningeal artery as it courses to the posterior temporal region to innervate the auricle.3 The terminal branch of the inferior alveolar nerve is the mental nerve, which supplies the skin of the lower lip and chin. Analogous to the V1 and V2, the mandibular nerve also relays parasympathetic fibers from cranial nerve seven, which supply the submandibular and sublingual glands. Additionally, the mandibular nerve carries secretomotor fibers from cranial nerve nine to innervate the parotid gland. The motor fibers of the mandibular nerve are essentially responsible for innervating the muscles of mastication including the temporalis, masseter, medial and lateral pterygoids, and the anterior belly of the digastric muscle. Thus, proper functioning of the mandibular nerve is essential for movement of the mouth and chewing.

Although the trigeminal nerve allows for the perception of both touch and pain, these facial sensations are relayed to the sensory cortex through two distinct pathways. Touch fibers from the trigeminal nerve synapse on the main trigeminal nucleus located in the pons. These fibers are then carried along the trigeminal lemniscus to the ventral posteromedial nucleus of the thalamus, which in turn runs to the sensory cortex.5 Pain fibers differ in that they synapse onto the spinal trigeminal nucleus, located primarily in the medulla, before using the trigeminothalamic tract to ascend into the thalamus and eventually the primary somatosensory cortex.2

Classification: Classic vs Secondary
The International Headache Society has separated TN into two categories: classic and secondary. While both categories present with similar symptoms, they differ in respect to their causality. Classic TN includes neuralgia that is idiopathic or caused by compression of the trigeminal nerve from a nearby blood vessel. Secondary TN, on the other hand, accounts for cases triggered by other structural abnormalities. Research has demonstrated that the classic form is accountable for roughly 80% of the cases of TN.6 The vessel that is most commonly associated with classic TN is the superior cerebellar artery, although other vessels, including the anterior inferior cerebellar artery, have been documented.7 The relationship between TN and neurovascular compression was examined by Hamlyn in a study of 46 patients. Of the 46 cases, 91% had a vessel that was compressing the trigeminal nerve.8

As noted, several systemic disorders have been attributed to the development of secondary TN, including multiple sclerosis and sarcoidosis. Other common triggers for secondary TN are tumors and skull base abnormalities particularly in the posterior fossa. Tumors ranging from vestibular schwannomas to meningiomas have been known to cause TN. It should be noted that patients with secondary TN are typically younger than those with classic TN.9 This age disparity could possibly be attributed to the underlying etiologies associated with the secondary form (Table 1).

Variability in Presentation
Although both forms of TN are characterized by exquisite facial pain, there are subtle differences in their presentation in the clinical setting. Patients with TN of either category usually present with a prolonged history of intermittent facial pain that can be localized over the distributions of one or more branches of cranial nerve five. Research has shown that V2 and V3 are involved, either alone or together, in an overwhelming majority of cases, while V1 is only involved fewer than 5% of the time.10 Patients provide a history of sharp, intense facial pain that lasts several seconds with repeated attacks throughout the day. These attacks can recur up to a few hundred times per day and continue for weeks or months. While a large percentage of patients will report shooting pain from the corner of their mouth to the angle of the mandible, variation exists both in the quality and distribution of pain experienced by patients.

The classic pain associated with TN is described as “shock-like” and is provoked by various triggers, such as touching or moving a specific area of the face. Other triggers can range from talking to washing one’s face. This disparity in associated triggers leads some patients to continually hold their face while talking, or avoid shaving. Occasionally, patients may begin to lose large amounts of weight due to the continual fear that eating may instigate an attack. These repeated episodes can last for weeks or months and may remit for an extended period of time, making the natural history of the disease difficult to predict; however, some clinicians believe that exacerbations are more common in the spring and fall. While the timing and triggers associated with these attacks seem to be unpredictable, patients rarely report pain that interrupts their sleep.

The atypical pain that sometimes accompanies TN presents as a more chronic, burning sensation that encompasses a larger facial surface area. The distribution of atypical pain may even extend to the neck and posterior scalp. Given the variation in presentation associated with TN, the diagnosis requires a high index of clinical suspicion. Patients suffering from TN may spend years in agony because of the lack of experience practitioners have with this condition. It is not uncommon for patients to undergo several unnecessary dental procedures due to the improper understanding of the pain source. Physicians can identify cases of TN in the early stages by keeping in mind that many patients initially present with dull, achy jaw pain referred to as “pre-trigeminal neuralgia” before the onset of the more severe stabbing pain.11 Additionally, TN can be differentiated from other causes of facial pain by the characteristic facial spasm that sometimes accompanies the episodes of pain, hence the term tic douloureux.5

Table 1. Characteristics of Classic vs Secondary Trigeminal Neuralgia

 

Classic

Secondary

Age of Onset

Over 50 years

Childhood to adulthood

Incidence

80% of trigeminal neuralgia

10% of trigeminal neuralgia

Etiology

91% caused by compression of nerve, most commonly superior cerebellar artery

Caused by structural abnormalities, such as multiple sclerosis or tumors

 

Imaging techniques have proven to be of limited use in the diagnosis of trigeminal neuralgia. With respect to the detection of neurovascular compression, magnetic resonance imaging (MRI) and magnetic resonance angiogram have shown mixed results. Currently, the American Academy of Neurology does not endorse the use of MRI to detect neurovascular compression when classic TN is suspected.12 However, the use of MRI has shown to be beneficial in differentiating classic versus secondary TN. Through an extensive review of the medical literature, Gronseth et al have concluded that MRI detects structural abnormalities in approximately 15% of patients already diagnosed with TN.12The identification of these secondary etiologies, such as tumors, can drastically alter the treatment strategy for these patients.

Clinicians may also distinguish secondary from classic TN through some common presenting features. For instance, patients with secondary TN frequently complain of facial sensory deficits and bilateral painful episodes along the branches of the trigeminal nerve, whereas the classic form is not associated with sensory loss and the pain distribution is typically unilateral.13 Furthermore, patients with secondary TN have been shown to have abnormal trigeminal reflexes, such as the blink reflex, in addition to the repeated bouts of pain.14 The blink reflex, or corneal reflex, refers to the closing of the eyelids after stimulation of the cornea. While the efferent limb of this reflex is mediated by the facial nerve (cranial nerve seven), the afferent limb is mediated by the ophthalmic branch of the trigeminal nerve. Therefore, in patients presumed to have TN of secondary origin, disruption of the afferent limb of the corneal reflex should be anticipated.

Pathophysiology
In recent years, there have been tremendous advances in our understanding of the pathogenesis of TN. While this disorder is divided into two broad categories in terms of etiology, the inciting event in both classifications seems to be demyelination of the trigeminal nerve. Demyelination refers to the destruction of the protective insulating sheath (myelin) on the outside of a neuron. Without a myelin sheath, nerve conduction becomes compromised resulting in an impairment of sensation, movement, etc. In classic TN, blood vessels contact the trigeminal nerve resulting in local areas of demyelination.15 Thus, the arteriolar thickening that occurs with aging clarifies the increased prevalence of TN after the age of 50 years.16 This compression-induced demyelination also appears in secondary forms of TN caused by tumors. Furthermore, the hallmark of multiple sclerosis, another common secondary etiology, is nerve demyelination, providing additional evidence that this mechanism plays a significant role in the pathogenesis of TN.

The connection between demyelination of the trigeminal nerve and the repeated painful spells that epitomize this disorder relates to the various functions of cranial nerve five. As stated above, the trigeminal nerve carries touch, pain, and motor fibers, which innervate distinct regions of the face. The nerve fibers responsible for touch generally have large diameters with moderate amounts of surrounding myelin, while pain fibers have smaller diameters and less myelin around their borders. When demyelination occurs, touch and pain fibers from the trigeminal nerve are closely approximated and become electrically coupled resulting in a hyperactive state.16 This artificial synapse between touch and pain fibers allows ephaptic conduction to occur, which is essentially cross-talk between adjacent nerve fibers.15 The presence of ephaptic transmission illustrates how even a trivial movement on a patient’s face can elicit repeated episodes of pain.

Differential Diagnosis
For clinicians to conduct a proper work-up for TN, they must keep in mind other pathologies that present in a similar manner. For instance, the signs and symptoms of postherpetic neuralgia mimic those of TN. Appearing shortly after the disappearance of the shingles rash, postherpetic neuralgia presents as a sharp, burning pain along the distribution of the preceding rash, which is generally on the patient’s trunk. However, when the rash occurs on a facial dermatome, postherpetic neuralgia can easily be confused with TN. While a thorough history and physical can often distinguish the two neuralgias, clinicians should keep in mind that the pain of postherpetic neuralgia often occurs during sleep, while the facial pain experienced in trigeminal neuralgia interestingly rarely disturbs a patient’s sleep.

Cluster headaches are another common cause of facial pain that should be considered when TN is suspected. Cluster headaches present as repeated attacks of unilateral orbital pain, which may recur several times per day. Although TN predominately affects V2 and V3 nerves, pain along V1 occurs in 5% of cases.10 This, in combination with the paroxysmal nature of cluster headaches, makes the distinction between the two conditions less obvious. Clinicians need to be aware that cluster headaches occur predominately in men, whereas TN has a female predominance. Additionally, cluster headaches are noted for the autonomic symptoms that accompany the facial pain, including lacrimation and rhinorrhea.

Vascular compression and tumor-induced demyelination may also affect other cranial nerves, resulting in an analogous presentation to TN. Glossopharyngeal neuralgia is a neuropathic disorder that disrupts the function of cranial nerve nine and occasionally cranial nerve ten. Given the similar inciting events and pathophysiology, it is no surprise that both conditions are characterized by repetitive attacks of electric pain that are triggered by innocuous facial movements, such as talking and chewing. To differentiate TN and glossopharyngeal neuralgia, the distributions and functions of each cranial nerve must be recognized. As stated above, the trigeminal nerve provides sensation to the face through three major branches; therefore, the pain elicited by TN will occur along those underlying facial distributions. Cranial nerves nine and ten provide sensation to the nasopharynx, oropharynx, and parts of the ear. Thus, patients with glossopharyngeal neuralgia will describe recurrent pain occurring in the ear and throat regions.17

Summary
The purpose of part one of our two-part series was to illustrate the etiology and typical presentation of TN. While not the most common cause of facial pain, TN must be considered by physicians when presented with a patient experiencing continuous facial discomfort. The severity of pain associated with TN and its devastating psychological effects make prompt diagnosis and treatment essential. Without a proper understanding of its clinical features and medical course, TN may go undiagnosed for years, creating an unacceptable quality of life for patients. After a diagnosis is established, clinicians must determine whether the cause of TN is secondary or idiopathic since the treatment regimens differ based upon the underlying etiology. With a proper diagnostic work-up and early treatment, patients inflicted with this potentially overwhelming neuropathic disorder may achieve pain relief within weeks and resume a healthy and productive life.

 

 

Last updated on: October 29, 2014
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