Medical Causes of Facial Pain
Part II

Hossein Ansari, MD

Director of Headache and Facial Pain Clinic at Kaizen Brain Center

Facial pain can be due to a variety of medical conditions.

The structure of the face is supplied by a nerve called the trigeminal nerve, which is one of 12 cranial nerves originating from the brain. The area of the brain from which the trigeminal nerve originates is called the “trigeminal nerve entry zone” (Figure 1). As it leaves the brain, the nerve collects in the area called the “trigeminal ganglion” (Figure 1). The trigeminal ganglion then splits into three trigeminal nerve branches, and enters the face. The three branches of the trigeminal nerve are responsible for sending pain, touch, and temperature sensations from the face to the brain. Any disorder affecting the trigeminal nerve from its origin in the brain up through its smallest branch in the teeth and face, that can cause pain is generally referred to as trigeminal neuropathic pain.

Figure 1 – Trigeminal nerve course from origins to face

The most well-described cause of trigeminal neuropathic pain results from vascular compression at “trigeminal entry zone” inside the brain, known as “classical trigeminal neuralgia.” However, any medical condition that can affect the trigeminal nerve, could potentially cause facial pain in the form of trigeminal neuropathic pain.

Autoimmune Disorders

Autoimmune disorders are the most common medical condition that can involve the trigeminal nerve. This involvement could be inside the brain, right in the area where the trigeminal nerve starts, or it can occur outside of the brain. In the fall 2020 issue of the Facial Pain Association Quarterly journal, we discussed autoimmune disorders involving the trigeminal nerve outside the brain, such as Sjögren syndrome. In this article, we will review conditions affecting the trigeminal nerve inside the brain.

Multiple Sclerosis

Multiple sclerosis (MS) is the leading cause of autoimmune disorder that can attack the trigeminal nerve inside the brain. 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 trigeminal neuralgia. This is about 400 times more often than the general population. The prevalence of TN in the MS population has been reported to be between 1% and 6.3%. Trigeminal neuralgia is sometimes an early symptom in MS. In fact, in about 10% of MS patients diagnosis of trigeminal neuralgia preceded the diagnosis of multiple sclerosis by an average of five years.

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

Figure 2 Structure of a neuron with two main components

In order to understand why MS can cause trigeminal neuralgia, a short introduction regarding the nervous system is required. Nerve cells called neurons have two main components (Figure 2):

Axons are a key component of a neuron. They conduct electrical signals between neurons.

Myelin: an axon is insulated by a sheath throughout its length to increase the velocity of these electrical signals, thus allowing signals to propagate quickly. This sheath or cover of the axon is referred to as the myelin.


Demyelination occurs when the myelin sheath is damaged. These demyelinated nerves have spots, or plaques, with no myelin (Figure 3) When this damage occurs to the myelin sheath, electrical signals from the axons misfire when they are not supposed to fire. This increased electrical activity presents with pain, which classified as neuralgic pain.

Other than multiple sclerosis, 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
• Vitamin B12 deficiency

Figure 3 – a demyelinated neuron in multiple sclerosis compared with a normal neuron

Therefore, it is not surprising that trigeminal neuralgia is more common in patients with multiple sclerosis than in the general population. For these patients, their facial pain can be confused with other pain, particularly dental pain. People with MS are 20 times more likely to experience trigeminal neuralgia than those without MS. Neuropathic pain is a common symptom in patients with MS. Among the different types of neuropathic pain, TN is a characteristic and difficult-to-treat neuropathic pain condition, with a relevant impact on the quality of life. Patients with MS experiencing TN find that daily life activities, work, mood, recreation, and overall quality of life can be disrupted.

Trigeminal Neuralgia Secondary to MS

Trigeminal neuralgia secondary to MS is, like the classical TN, characterized by a sudden, brief, jabbing, and electrical 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 two minutes, and are typically provoked by simple stimulating of skin or mucosa of the face and/or mouth. The pain can be triggered by every day routine activities such as chewing, talking, brushing teeth, or by being outside in a light breeze. However, features that should raise the question of trigeminal neuralgia due to MS or other autoimmune conditions include:

Bilateral trigeminal neuralgia

It is extremely uncommon that classical trigeminal neuralgia occurs on both sides of the face, or bilaterally. In MS, an estimated 18% of patients reported to have bilateral trigeminal neuralgia. Therefore, any patient presenting with bilateral facial pain requires a very detailed work up with particular attention to ruling out MS as its cause.

Pronounced sensory changes

Patient 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 on other parts of body, including feet and hands.

Continuous/constant pain from the onset of facial pain

Patients with continuous face pain can misattribute the pain to dental pain. Bearing in mind that facial pain could be a symptom of MS-related trigeminal neuralgia, 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, suffer from concomitant continuous, dull or burning pain between attacks of electric shock pain. The area of continuous pain is the same area of paroxysmal pain and the intensity of pain fluctuates between the episodes of those paroxysmal pain cycles. Therefore, a detailed history in addition to a sensory exam is very important to make a correct diagnosis and work up.

Younger age of onset, particularly below age 40

It is rare for people under 40 to experience classical trigeminal neuralgia so, for those in this age range, it is particularly important to consider other causes of TN such as MS.

How Trigeminal Neuralgia Due to MS Can be Diagnosed

If after a detailed history and exam, if your physician suspects the possibility of MS as the potential reason for TN, a proper work up needs to be initiated which includes:

Magnetic Resonance Images (MRI)

A brain MRI, and in some cases cervical spine, MRI looks for changes caused by multiple sclerosis, such as signs of inflammation in the deep parts of the brain or spinal cord. This is 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 with 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 people with MS, we might not be able to see the lesion(s) in an MRI, or it could simply be too early in the disease to detect the lesion. If trigeminal neuralgia is the only suspected symptom, we usually do not recommend further work up, but if there is high suspicion for MS due to some other neurological symptoms, additional work up might be indicated as below.

Spinal tap (lumbar puncture)

This test checks the fluid that runs through the spinal column. We use this test to look for high levels of proteins and other substances that are signs of MS or a related demyelinating disorder.

Evoked potentials

These electrical nerve tests can help confirm if MS has affected the parts of brain that help you see, hear, and feel sensations. In this test, some wires will be 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 we order them to look for substances in blood that point to it. Most importantly, a blood test will help rule out conditions that look like MS.

Neurophysiological tests

“Trigeminal reflex testing,” particularly, which is abnormal in 89% of patients with TN secondary to MS, but in abnormal in only 3% of patients with classical and idiopathic TN. This might be a very helpful test in patients unable to get MRI due to metal in their body such as a pacemaker.

Treatment of trigeminal neuralgia in MS

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 is pharmacological and is based, as it is for classical and idiopathic TN, on the use of sodium-channel blockers like 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 last decade, early and proper treatment of this condition might prevent progression of disease, and as a result, also prevent the progression of trigeminal neuralgia. Surgical treatment, particularly microvascular decompression, is less successful in TN secondary to MS.


The FPA does not endorse any product, doctor, procedure, medical institution, or its staff.

Note from Medical Editor, Dr. Jeffrey Brown

Dr. Jannetta’s understanding of how a blood vessel could injure the trigeminal nerve is that ongoing pulsations lead to loss of the fatty covering on thousands of the wires contained in the cable that is the trigeminal nerve. This leaves “naked” nerves in contact and allows the short circuits that are perceived as shocks. Thus, “compression” is not the cause of trigeminal neuralgia. An analogy is that the nerve is being repeatedly “punched”, not constantly “squeezed.” These pulsations cannot be seen on a single image created by an MRI machine. However, the damage to the nerve has been documented by looking at nerve biopsies taken from just below the vessel moved at surgery.

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