2.10 Medical Causes of Facial Pain

By Hossein Ansari, MD, FAAN, FAHS (USA)

Facial pain is one of the most challenging entities for physicians to treat. This is due to the variety of its causes. These include neurological, dental (e.g., temporomandibular joint disorders, tooth and gum issues), and sinus – and nasal-related causes, as well as those related to rheumatologic and autoimmune disorders. This chapter discusses three autoimmune disorders that can cause facial pain: Sjögren’s syndrome, scleroderma, and MS.

Nerve supply to the face comes from the trigeminal nerve, which is one of the 12 cranial nerves in the human body. A cranial nerve is one that directly enters or leaves the brain. The trigeminal is composed of three (prefix “tri-”) main divisions. Each division has multiple branches that funnel down to the main sensory root before entry into the brain stem, as depicted in Figure 2-7.

Figure 2-7. Multiple small branches of the trigeminal nerve.

These branches supply the sensation to different parts of the face, mouth, tongue, nose, and sinuses. Any damage, injury, or disease that affects the trigeminal nerve anywhere from the smallest branches on the face to its origin in the brain can cause facial pain.

The evaluation of a person with facial pain includes both gathering a thorough history and examining the head, teeth, eyes, nose, throat, and even neck, because any of these structures can contribute to facial pain. Because of this heterogeneity of causes, individuals with facial pain often need to consult multiple practitioners to obtain a proper diagnosis and treatment.

Most of the time, facial pain is triggered by some form of trauma: a dental procedure, compression of nerves by blood vessels, or invasion by a tumor. Medical disorders that affect the trigeminal nerve can be a source of facial pain. In general, any pain that occurs as a result from an injury to a nerve is referred to as a neuropathic pain. This definition is broad and covers more than 100 conditions. When the injury to the trigeminal nerve occurs in the brain due to compression by blood vessels, it is also known as trigeminal neuralgia (TN).

The most challenging cases of trigeminal neuropathic pain involve people with facial pain who do not have classical TN. Classical TN refers to intermittent facial stabbing pain with intervening pain-free periods. Other people are often labeled as having atypical facial pain or atypical TN. Some of these people may have a systemic medical disorder that also involves the trigeminal nerve, causing facial pain.

Among systemic medical causes, inflammatory and autoimmune diseases are the most common disorders that involve trigeminal nerves. Autoimmune diseases such as Sjögren’s syndrome, scleroderma, lupus, and undifferentiated connective tissue disorder, can attack the trigeminal nerve and cause facial pain, sometimes similarly to TN. Individuals experiencing facial pain due to autoimmune diseases are said to have inflammatory trigeminal neuropathy or autoimmune trigeminal neuropathic pain. Surgery will not help these disorders.

Sjögren’s syndrome is a chronic, systemic autoimmune disease that is more common in women. It is one of the more prevalent autoimmune disorders. Because its symptoms are sometimes mild, it might not be diagnosed. The main targets of Sjögren’s syndrome are the exocrine glands, such as the parotid or salivary glands, which causes dryness of the mucosal surfaces. Dry eyes and dry mouth are the key features of this syndrome. If Sjögren’s syndrome does not affect any other organs, it might not even be diagnosed solely on the basis of dry eyes or dry mouth because these symptoms are nonspecific and common in the general population. However, in Sjögren’s syndrome, a variety of systemic manifestations may occur, including fatigue, musculoskeletal symptoms, cutaneous lesions, and internal organ and neurological involvement. According to some reports, up to 70% of Sjögren’s patients may experience neurological manifestations.

Neuropathy is a classic neurological manifestation of Sjögren’s syndrome; thus, trigeminal nerve involvement could occur in individuals with Sjögren’s syndrome. In fact, the trigeminal nerve is the most common cranial nerve to be involved. As a result, in patients who have trigeminal neuropathy due to Sjögren’s syndrome, with no other cranial nerve involvement, facial and trigeminal pain will be the only major symptoms of Sjögren’s because the symptoms of dry eyes or dry mouth could be mild.

In patients with facial and trigeminal pain who do not have classic TN, the presence of some nonspecific symptoms could suggest the possibility of Sjögren’s syndrome. These symptoms could include

• Unexplained fatigue or tiredness;
• Severe dry eyes that require treatment (Symptoms of dry eyes include stinging, burning, or itching; feeling of sand in the eyes; sore and swollen eyelids; discomfort when looking at light; and even blurry vision.);
• Severe dry mouth, which can present with the tongue sticking to the roof of mouth, feeling that food (specifically dry food) is stuck in the mouth or throat, and even changes in how food tastes;
• Frequent dental cavities despite good dental hygiene;
• Dry skin or vaginal dryness;
• Rashes (especially after being in the sun);
• History of multiple unexplained miscarriages; and
• Muscle and joint pain with stiffness and swelling.

These are symptoms that are usually not asked about by physicians if patients present with facial and trigeminal pain. Therefore, patients should be aware of this disease and pay attention to those nonspecific symptoms, particularly when they are diagnosed with atypical TN or atypical facial pain.

The diagnosis of Sjögren’s syndrome is not always easy because the blood test for Sjögren’s could be negative in up to 40% to 50% of patients with this syndrome. This is particularly true in people who are in the beginning of the disease process because their bodies have not made enough antibody to be detected. Therefore, in individuals with facial pain for whom there is a question of Sjögren’s syndrome, consultation with a rheumatologist might help to obtain proper diagnosis and treatment.

Scleroderma is a chronic autoimmune disorder that is much less common than Sjögren’s syndrome. However, because trigeminal nerve involvement is one of the most common manifestations of this autoimmune disease, it should be considered as a potential cause of facial pain. Scleroderma, similarly to Sjögren’s syndrome, is more common in young to middle-aged women with peak onset at ages of 30 to 50 years.

Patients with scleroderma can have progressive skin tightness and induration, often preceded by swelling and puffiness. The other important symptom that can be suggestive of scleroderma is Raynaud’s phenomenon. With Raynaud’s phenomenon, there is a pale to blue to red sequence of color changes of the fingers or toes, most commonly after exposure to cold (Figure 2-8).

Figure 2-8. Color changes of the fingers and toes with Raynaud’s phenomenon.

Raynaud’s phenomenon is more characteristic of scleroderma, but it can be seen in other autoimmune disorders. Raynaud’s phenomenon that is not associated with systemic sclerosis or other autoimmune diseases is known as primary Raynaud phenomenon. It occurs in 5% to 15% of the general population.

In addition to skin manifestation, scleroderma, similarly to Sjögren’s syndrome, has many nonspecific symptoms, including

• Gastrointestinal symptoms, which can range from dyspepsia, bloating, and reflux to difficulty swallowing;
• Respiratory symptoms, such as progressive shortness of breath, chest pain, and dry persistent cough;
• Musculoskeletal symptoms, such as severe muscle pain, fatigue and weakness, and joint pain with loss in joint range of motion; and
• Kidney involvement, which typically presents as early-onset hypertension, which is usually resistant to regular treatment and can sometimes cause renal failure.

Bear in mind that the symptoms in Sjögren’s syndrome and scleroderma, as well as other autoimmune disorders that can attack the trigeminal nerve, can be nonspecific. The entire clinical picture needs to be considered before suggesting these possibilities as the reason for facial pain. The most important factor is age of the onset of trigeminal pain. Because classical TN, which is the most well-known etiology for facial pain, is rare before the age of 40 years and unusual before the age of 50 years, individuals with facial pain in those age groups need to be aware of the possibility of an autoimmune disorder. This is particularly true because the most common age for the onset of autoimmune disorders is between 20 and 50 years.

Sjögren’s syndrome and scleroderma are autoimmune disorders involving the trigeminal nerve outside the brain. In contrast, the third condition considered here affects the trigeminal nerve inside the brain, namely, MS.

MS is an autoimmune disorder in which the immune system attacks the myelin sheath around its own nerves. Recent research suggests that between four and six of every 100 people with MS experience TN. This is about 400 times more often than in the general population. The prevalence of TN in the MS population has been reported to be between 1% and 6.3%. TN is sometimes an early symptom in MS. In 10% of individuals with MS, the diagnosis of TN preceded the diagnosis of MS by an average of 5 years.

Different people experience the pain of MS-related TN in different ways. It is most commonly felt in the cheek or in the upper or lower jaw, but some individuals experience pain up toward the eye, ear, and forehead or inside the mouth.

To understand why MS can cause TN, a short introduction of the nervous system will help. Nerve cells called neurons have two main components (Figure 2-9):

Figure 2-9. Structure of a neuron with its axon surrounded by myelin.

• Axons are a key component of a neuron. They conduct electrical signals between neurons.
• Myelin is the sheath or cover of an axon. Each axon is insulated by this sheath throughout its length to increase the velocity of the electrical signals it transmits, thus allowing signals to propagate quickly.

Demyelination occurs when the myelin sheath is damaged. Demyelinated nerves have spots, or plaques, with no myelin (Figure 2.10). When this damage occurs to the myelin sheath, electrical signals from the axons misfire when they are not supposed to fire.

Figure 2-10. Comparison between a normal neuron and a demyelinated neuron in multiple sclerosis.

This increased electrical activity presents as pain, which is classified as neuralgic pain.

Other than MS, myelin damage can be caused by any number of common and uncommon conditions. These include

• Infections,
• Inflammation,
• Metabolic disorders,
• Certain medications,
• Excessive alcohol use,
• Stroke, and
• Vitamin B12 deficiency.

Similar to classical TN, TN secondary to MS is characterized by a sudden, brief, jabbing, and electric-shock-like, recurrent pain with a distribution that is consistent with one or more branches of the trigeminal nerve. The paroxysmal attacks last from a fraction of a second to about 2 minutes and are typically provoked by simple stimulation of the skin or mucosa of the face and/or mouth. The pain can be triggered by everyday routine activities such as chewing, talking, or brushing teeth or even by being outside in a light breeze. However, characteristics that should raise the question of TN due to MS or other autoimmune conditions include the following:

• Bilateral trigeminal neuralgia. It is uncommon for classical TN to occur on both sides of the face, or bilaterally. In MS, an estimated 18% of patients have bilateral TN. Therefore, any patient presenting with bilateral facial pain requires a detailed work-up with particular attention to ruling out MS as its cause.
• Pronounced sensory changes. Patients who complain of significant sensory symptoms, either tingling or numbness on the face, are more likely to have an autoimmune condition, including MS. This is even more likely if patients have additional sensory symptoms in other parts of body, including feet and hands.
• Continuous or constant pain from the onset of facial pain. Patients with continuous face pain can misattribute the pain to dental causes. Bearing in mind that facial pain could be a symptom of MS-related TN, it is always helpful to keep this possibility in mind, especially before considering any major dental work. On the other hand, some patients with TN secondary to MS, such as patients with other types of TN, experience concomitant continuous, dull, or burning pain between attacks of electric-shock-like pain. The area of continuous pain is the same as the area of paroxysmal pain, and the intensity of the pain fluctuates between the episodes of those paroxysmal pain cycles. Therefore, a detailed history, in addition to a sensory exam and thorough work-up, is especially important to make a correct diagnosis.
• Younger age of onset, particularly below 40 years of age. It is rare for people under the age of 40 years to experience classical TN, so for those in this age range, it is particularly important to consider other causes of TN such as MS.

If, after a detailed history and exam, your physician suspects the possibility of MS as the potential reason for TN, a proper work-up needs to be initiated. Such a work-up should include the following components:

• MRI scan. An MRI scan of the brain, and in some cases, of the cervical spine, should be performed to look for changes caused by MS, such as signs of inflammation in the deep parts of the brain or spinal cord. Such changes are called MS plaques. TN secondary to MS is usually associated with a plaque in the area of brain called the pons, which is easily detectable by MRI. In most patients, MRI is enough to make the diagnosis. However, a normal MRI result does not rule out MS. In a small number of individuals with MS, it might not be possible to see the lesion(s) in an MRI scan, or it could simply be too early in the disease to detect the lesion(s). If TN is the only suspected symptom, further work-up is usually not recommended, but if there is a high suspicion of MS due to some other neurological symptoms, additional work-up might be indicated, as discussed further in the remainder of this list.
• Spinal tap (lumbar puncture). This test checks the fluid that runs through the spinal column. It is used to look for high levels of proteins and other substances that are signs of MS or a related demyelinating disorder.
• Evoked potential tests. These electrical nerve tests can help confirm whether MS has affected the parts of the brain that help with seeing, hearing, and feeling sensations. In these tests, some wires are placed on the scalp to test the brain’s response as the patient watches a pattern on a video screen, hears a series of clicks, or receives electrical pulses on the arms or legs.
• Blood tests. There is no blood test to diagnose MS, but blood tests are used to look for substances in the blood that point to it. Most importantly, a blood test can help rule out conditions that look like MS.
• Neurophysiological tests. Results of trigeminal reflex testing, in particular, are abnormal in 89% of patients with TN secondary to MS, but they are abnormal in only 3% of patients with classical and idiopathic TN. This might be an extremely helpful test in patients unable to obtain MRI testing because of metal in their body such as a pacemaker.

According to international guidelines, there is insufficient evidence to support or refute the effectiveness of any medication in treating pain in TN secondary to MS. However, it is generally agreed that the first-line therapy for this pain is pharmacological and is based, as it is for classical and idiopathic TN, on the use of sodium-channel blockers such as oxcarbazepine or carbamazepine. It is critical that patients with MS treat their MS with medication that is specific for this condition. With advancements in medication for MS in the past decade, early and proper treatment of this condition might prevent the progression of disease and, as a result, also prevent the progression of TN. Surgical treatment, particularly MVD, is less successful in TN secondary to MS.