Burning mouth syndrome/glossodynia and trigeminal neuropathic conditions can have serious negative impact on a patient’s overall quality of life. These conditions are often hard to diagnose and even harder to fully treat and manage, but it is important for dentists/oral and maxillofacial surgeons to be aware of these conditions and modalities of their treatment. Often the only method for arriving at the proper diagnosis is for patients to undergo traditional approaches for treatment of presenting signs and symptoms, and it is the unexpected failure of interventional therapies that leads ultimately to a proper diagnosis.
Burning mouth syndrome/glossodynia and trigeminal neuropathic conditions can have serious negative impact on a patient’s overall quality of life.
These conditions are often hard to diagnose and even harder to fully treat and manage, but it is important for dentists/oral and maxillofacial surgeons to be aware of these conditions and modalities of their treatment.
Often the only method for arriving at the proper diagnosis is for patients to undergo traditional approaches for treatment of presenting signs and symptoms, and it is the unexpected failure of interventional therapies that leads ultimately to a proper diagnosis.
The overwhelming reason that causes most patients to visit the dentist or oral and maxillofacial surgeon is the onset (either acute or chronic) of some form of orofacial pain. Clinicians who wish to develop a successful practice must be knowledgeable in performing a thorough systematic head/neck and oral examination as well as in interpreting appropriate imaging studies so as to be able to arrive at the correct diagnosis in order to properly alleviate the patient’s pain.
The predominant cause of most patients’ orofacial pain upon visiting a dental/oral surgery provider will be of dental or periodontal origin. Patients presenting with pain secondary to a temporomandibular joint disorder (TMD) is another frequent reason for patients seeking respite from their facial pain. TMD involves the masticatory system, the temporomandibular joint (TMJ), or more commonly a combination of the two. The National Institutes of Health reported in 2014 that the prevalence of TMD with signs and symptoms range from 5% to 12%, based on studies from around the globe.
Other possible causes of oral/facial pain are sinus conditions, salivary infections, headaches, migraines, vascular disorders, and neuropathic pain syndromes. Patients with chronic facial pain are often also plagued with comorbidities, such as depression, anxiety, along with other chronic pain disorders.
This article focuses on 2 distinct subjects: burning mouth syndrome (BMS)/glossodynia and trigeminal neuropathic conditions. Both of these entities can have serious negative impact on a patient’s overall quality of life. These conditions are often hard to diagnose and even harder to fully treat and manage, but it is important for dentists/oral and maxillofacial surgeons to be aware of these conditions and modalities of their treatment. It is not unusual for patients who suffer from trigeminal neuropathic pain to have undergone almost full-mouth root canal therapy only to have all their teeth extracted in a desperate attempt to alleviate their chronic orofacial (neuropathic) pain. Often the only method for arriving at the proper diagnosis is for patients to undergo traditional approaches for treatment of presenting signs and symptoms, and it is the unexpected failure of interventional therapies that ultimately leads to a proper diagnosis.
Neuropathic pain is currently defined by the International Association for the Study of Pain as pain caused by a lesion or disease of the somatosensory nervous system. The neuropathic pain may present as a dysesthesia or pain from normally nonpainful stimuli. It may be continuous or episodic in nature. By neuropathy, the authors mean a continuous pain signal generated within the nervous system without adequate stimulation of the peripheral sensory neurons. This article reviews various chronic neuropathic pain conditions.
Central Pain Syndrome
Central sensitized pain is defined as increased or amplification of pain within the central nervous system (CNS) that causes pain hypersensitivity and that causes an increased painful response to painful stimuli and nonpainful stimuli, referred to as hyperalgesia and Allodyna. This disease process starts and is perpetuated by the CNS. This disorder may be caused by inflammation, structural mechanisms, and central causes. ,
Patients are diagnosed with centralized pain by the duration and distribution of the pain. If the patient has developed pain for the last 3 months that is consecutive and widespread. These symptoms should also be in addition to sleep disturbance, fatigue, and changes in mood. This disease process can only be diagnosed after a peripheral cause of pain has been ruled out as a diagnosis.
After performing a thorough examination and recording the duration, severity, and location of pain, the provider must perform a thorough musculoskeletal examination and laboratory testing, which includes a complete blood count, erythrocyte sedimentation rate, or a C-reactive protein level. These diagnostic laboratory tests provide a measure of the acute phase response.
According to the European Federation of Neurological Sciences guidelines from 2010, the pharmacologic treatment of centralized neuropathic pain includes tricyclic antidepressants (TCAs) as the first line of treatment, gabapentin, and lamotrigine. Other pharmacologic treatments that have been used include phenytoin, carbamazepine, and clonazepam. Transcutaneous electrical nerve stimulation has been shown to provide alleviation. Surgical intervention is only appropriate after noninvasive methods have failed.
Neuropathic pain mechanisms
Through various methods, such as inflammation, injury, and trauma, afferent fibers can become sensitized. Usually this pain is self-limiting and resolves after inflammation and swelling have resolved. In cases where pain is caused by disease or permanent loss of afferent fibers (deafferentation), this pain will progress as central in nature. “This pain modality usually occurs when intact nerve roots, tracts, and nerves are partially or entirely disrupted. This usually occurs after trauma or peripheral nerve injury. This phenomenon can also be present after formation of lesions along central tracts or damage to posterior rootlets.”
To the dentist or oral surgeon, it is possible to have patients experience deafferentation pain after an extraction or endodontic procedure. Both of these procedures cause the removal of nerve tissue from/with the tooth. Most patients complain of dull and aching pain, sharp needlelike pain, or burning sensation. The painful sensation is caused by “hypersensitivity of the central neurons, damaged cells, decrease in inhibition, and increase in facilitation at the lesion site.” Patients report alleviation of this pain with the help of local anesthetics. Deafferent pain is resistant to morphine treatment but affected by barbiturates.
Patients who have undergone radical neck dissections and have had branches of the trigeminal nerve sacrificed may present with deafferentation pain.
Sympathetic Mediated Pain
Triggered by the autonomic nervous system, “[s]ympathetic mediated pain results from a nociceptive process rather than a noxious stimuli.” Signaling begins in the afferent pathway by catecholamines. A-1 adrenoreceptors are increased in the skin of chronic pain conditions, thus increasing sympathetic mediation. Sympathetic neurotransmitters do not activate sensory nerves; however, when the sensory nerves are sensitized because of injury or chronic pain situations, the nerve upregulates the receptors to respond to sympathetic signals. This sympathetic pain presents as flushing, abnormal skin temperature in the painful area, and sweating. ,
Traumatic injury can lead to a chronic pain condition called complex regional pain syndrome (CRPS), which is characterized by continuous pain and hyperalgesia. The efferent pathway continues sympathetic activation, thus continuing the release of catecholamines and facilitating pain. CRPS is thought to be caused by damage to the peripheral and central nervous systems. A surgical procedure (even minor procedures) can in certain individuals act to heighten this condition. This condition following oral procedures has been called “painful traumatic trigeminal neuropathy.”
Glossopharyngeal neuralgia is a far rarer neuropathic condition that involves the distribution of the glossopharyngeal nerve. Like Trigeminal Neuralgia, it is sudden, severe, and most commonly unilateral. Patients feel a stabbing pain along the glossopharyngeal nerve, such as the ear, base of tongue, tonsillar fossa, and beneath the angle of the mandible. The pain can be triggered by yawning, swallowing, chewing, and talking.
Psychiatric contribution to pain
Chronic pain syndromes usually accompany or are linked to psychogenic factors, such as depression, anxiety, bipolar disorder, and stress, making it very difficult to assess and diagnose pain disorders. Patients with a mental health diagnosis were twice as likely to be prescribed opioids compared with those without a diagnosis according to a prospective study by Closs. It is essential that these factors are recognized during the initial visit. Referring a patient for psychological therapy will assist in the treatment process.
“The nociceptive pathways are modulated by psychological processes which may amplify pain symptoms.” These patients must be treated with a multidisciplinary approach. These patients may have long-standing emotional, mental, and work-life stress contributing to their pain. A long discussion in an attempt to understand the patient’s pain and then possibly a referral to a mental health organization may assist in managing physical manifestation to a patient’s chronic pain status. Serotonin-norepinephrine reuptake inhibitors (SNRIs) and TCA have a strong contribution in the pharmacotherapy involved in treating patients with chronic facial pain, as detailed further in this article.
Migraine is an episodic disorder characterized by a severe headache that is associated with nausea, light, and sound sensitivity. This disorder is divided into 2 subtypes: migraine without aura (70% of cases) and with aura (30% of cases). Patients describe aura as an initial sign or symptom, such as flashing lights or blind spots in the vision. Once diagnosis is made by a neurologist or orofacial pain specialist, there is much that a dentist or oral surgeon can do to provide and manage a patient’s chronic migraines.
Patients typically present with complaints of severe, unilateral, throbbing headaches that can last from 4 hours to 3 days. Pharmacotherapy includes nonsteroidal anti-inflammatory drugs (NSAIDs) or triptans for acute therapy (described in detail in later discussion under the treatment section). Other commonly used medications include aspirin, ibuprofen, naproxen, ergotamine, sumatriptan, and zolmitriptan.
The practicing oral surgeon and dentist can now provide alternate preventative therapy: botulinum toxin type A. Botox is commonly used for cosmetic procedures to abolish wrinkles and fine lines of the skin and also in the treatment of myofascial pain disorders (described further in later discussion). Evidence suggests that botulinum toxin may inhibit the release of neuropeptides involved in pain perception and inflammation and has become a viable and effective option in the treatment of migraines.
To understand chronic pain diseases, it is important to understand the underlying pathophysiology. Even though it is still not clearly elucidated, there are 2 hypotheses that are present to describe the disease process. The “lesion” described in the definition above for neuropathic pain can be an irritative lesion that affects the somatosensory pathway; this can increase activity in the nociceptive pathway. The second hypothesis indicates that neurons in proximity of the lesion can become hyperactive and hypersensitive through denervation.
The pain conduction pathway is generally described as involving three orders of neurons that transmit the actual pain signal following activation of the nerve fiber. The first order neurons have special receptors called nociceptors-Three type of nociceptors exist mechanical, thermal and polymodal. Signals from these pain receptors are transmitted from the site of injury to the dorsal bone of the spinal cord predominantly by A- delta and C fibers (first order neurons) and once the CNS is activated this signal and information is transmitted by second order neurons to the thalamus and eventually by third order neurons to the higher cortical areas.
Clinical presentation of neuropathic pain
Patients will typically present with varying pain in severity, intensity, description, and area/location. Patients can report muscle pain that can be cramping, constricting, or crushing. Dysesthesias are common with a burning feeling that can be constant or intermittent. Pain can also be described as shooting, lancinating, or hyperpathic.
The patient will also describe triggers to their pain, such as cold, hot, movement, light touch, and emotional distress.
Neurologic pain can be (1) episodic or (2) continuous. Examples of episodic pain are trigeminal neuralgia and glossopharyngeal neuralgia. Examples of continuous neuropathic pain include herpetic neuralgia, postherpetic neuralgia, traumatic, neuralgia, and Eagle syndrome.
Trigeminal neuralgia is characterized by sharp, unilateral, stabbing pain that extends in one or more branches of the trigeminal nerve. This pain is most often triggered by various stimuli, such as light touch and vibrations. This disease process usually affects 1 side and usually the maxillary and mandibular division of the trigeminal nerve (shown in Fig. 1 ). Trigeminal neuralgia can present because of posterior fossa compressive lesions, intracranial tumors, or demyelinating plaques of multiple sclerosis. , Continuous afferent input of nerve impulses may produce central sensitization.
Neuroimaging will help distinguish classic TN to secondary TN. MRI is the preferred imaging technique with or without contrast because of the higher resolution. According to the International Classification of Headache Disorders, Third Edition, diagnostic criteria include the following: (1) recurrent paroxysms of unilateral pain along the distribution of the trigeminal nerve; (2) pain that lasts from a faction of a second to 2 minutes, severe in intensity, and electric in characteristic; (3) pain precipitated by innocuous stimuli; and (4) pain not accounted for by another diagnosis. The differential diagnosis includes compression of the trigeminal nerve, demyelination from multiple sclerosis.
Anesthesia dolorosa is also known as painful trigeminal neuropathy following an incidence of trauma, which produces unilateral facial pain and may be accompanied by trigeminal nerve dysfunction. Pain is superimposed in the area of that face that lacks or has impaired sensation. Diagnosis is achieved according to the International Classification of Headache Disorders, Third Edition: facial pain in the distribution of one or both trigeminal nerves, history of identifiable trauma to nerve with hyperalgesia, hypoesthesia, allodynia, and pain developed within 6 months of traumatic event.
Painful trigeminal neuralgia is most common in women (74:1; women:men) and is diagnosed in 5 out of 100,000 people.
Finding appropriate therapy for neuropathic pain can be difficult. Most treatment therapies include pharmacotherapy that reduces CNS activity, medications that enhance the reuptake of serotonin and noradrenaline and influence adrenoreceptors and electrical stimulation of central/peripheral nerves. Using an integrated multimodal biopsychological management plan is the most efficient way to provide treatment. The provider must timely recognize the pain syndrome by performing a thorough examination. Recognizing that a patient’s pain is not only a psychogenic illness allows patients from believing that the pain is only in their head.
Based on a systematic review of randomized clinical trials in various neuropathic pain conditions by the European Federation of Neurological Societies, there are strong recommendations on approaching treatment of neuropathic pain. These recommendations are described in later discussion.
Amitriptyline is a TCA most commonly used as a first-line agent. It is also known as the most effective tricyclic for central poststroke pain in treatment of neuropathic pain. It causes an increase in the synaptic concentration of serotonin and norepinephrine in the CNS by inhibition of their reuptake by the presynaptic neuronal membrane pump. It can be started at 10 to 25 mg nightly and titrated up until a maximum dose of 100 to 124 mg nightly is attained. This antidepressant along with other TCAs is sedating. Side effects include dry mouth, constipation, tachycardia, palpitations, orthostatic hypotension, weight gain, blurred vision, and urinary retention.
SNRIs are commonly used to treat depression by blocking presynaptic serotonin and norepinephrine transport proteins in the presynapsis. The specific class of drugs also have evidence of analgesic qualities similar to TCAs. The evidence for selective serotonin reuptake inhibitors (SSRIs) is not as potent as shown from a systematic review by Saarto and Wiffen.
Carbamazepine (Tegretol) is an anticonvulsant drug most commonly used for bipolar disorder, focal onset of seizures, and trigeminal neuralgia/glossopharyngeal neuralgia. Tegretol has anticonvulsant, anticholinergic, antineuralgic, antidiuretic, and antidepressant properties. It may depress activity in the nucleus ventral of the thalamus and decrease synaptic transmission by limiting influx of sodium ions across the cell membrane or other unknown mechanisms. It is used to treat neuropathic pain as a component of multimodal pain control. It may be initially started at 100 to 200 mg/d and gradually increased over several weeks in increments of 200 mg/d as needed to a maximum dose of 1200 mg/d. Although the side effects are rare, they are serious, such as agranulocytosis, aplastic anemia, and Stevens-Johnson syndrome.
Gabapentin is similar in structure to γ-aminobutyric acid (GABA) but does not bind to GABAa or GABAb receptors. It binds to high-affinity gabapentin binding sites in the brain that possess the alpha-2-delta-1 subunit, which modulates the release of excitatory neurotransmitters. Gabapentin is a type of anticonvulsant that is commonly used for the treatment of postherpetic neuralgia and neuropathic pain when the adverse effects of TCAs are to be avoided. Gabapentin is also known to relieve allodynia, burning, and shooting pain. Gabapentin is contraindicated in patients who have hypersensitivity to Gabapentin. It can be started at 300 mg daily and increased as needed for pain relief. Most patients feel adequate relief at a dose of 900 to 2400 mg. The most common side effects include somnolence, diarrhea, mood swings, ataxia, fatigue, nausea, and dizziness.
Pregabalin binds to the alpha-2-delta subunit of the calcium channel in the CNS at nerve terminals, thus inhibiting excitatory neurotransmitter release. It exerts an antinociceptive and anticonvulsant effect. It is a common medication used for fibromyalgia, neuropathic pain associated with peripheral neuropathy, and spinal cord injury. Pregabalin is contraindicated in patients with hypersensitivity to pregabalin. It can be started at 25 mg once daily to 50 mg 3 times per day. Higher doses can be given to the patient, but the total dose of 600 mg daily should not be exceeded. When the drug is discontinued, it should be tapered over a week or else withdrawal symptoms may present. Some common side effects include dizziness, somnolence, dry mouth, peripheral edema, and weight gain. Pregabalin can also cause sedation and confusion.
Capsaicin can be administered as a topical cream commonly used for neuropathic pain and muscle/joint pain and provides temporary relief of minor aches and pains of muscles and joints and mild relief in patients with diabetic neuropathy or postherpetic neuralgia. It acts as an agonist to the Vanilloid Receptor Subtype I (TRPVI). and activates ligand-gated cation channels on nociceptive nerve fibers. Binding to the TRPVI Receptor causes desensitization of sensory axons and inhibition of transmission initiation. If the topical cream causes irritation or erythema, it should be discontinued. The patient should apply the cream to the affected area 3 to 4 times daily.
Providing supplementation with analgesics is a very effective dual or triple therapy when treating chronic pain syndromes. After reviewing a patient’s medical history, a provider is advised to supplement main-line treatment methods with nonopioid analgesics, opioid analgesics, antidepressants, topical medications, and therapy.
Paraacetylaminophenol/acetaminophen is an over-the-counter analgesic and antipyretic that is commonly paired with an opioid to provide increased support or lower the dose of opioid needed. A dose of 325 mg to 600 mg every 6 hours is usually prescribed alongside other treatments. An overdose of acetaminophen can cause severe hepatotoxicity. The Food and Drug Administration (FDA) reports the maximum dose of acetaminophen at 4 g/d. It is contraindicated in patients with liver disease.
NSAIDs-naproxen is a type of NSAID that acts reversibly to inhibit the cyclooxygenase-1 (COX-1) and -2 enzyme, causing a decrease in the formation of prostaglandin. It has antipyretic, analgesic, and anti-inflammatory properties. It is one of the most commonly used analgesic medications throughout medicine. It is contraindicated in patients with a history of asthma, urticaria, or anaphylactic reactions. In treating patients with facial pain, start by dosing 500 mg every 12 hours for 2 weeks. The patient should be reevaluated in 2 weeks for improvement. Long-standing use of NSAIDs may cause gastrointestinal disturbances and is also not advised for patients with gastrointestinal conditions. Other NSAIDs include celecoxib (COX-2 inhibitors) and ibuprofen.
Facial pain is not limited to neuropathic pain. Patients may confuse neuronal pain with musculoskeletal pain. It is up to the dentist/oral surgeon to perform a thorough examination to distinguish the differences in these conditions and treat appropriately. Most patients who present with complaints of facial pain actually have pain caused by conditions that fall under the TMD classification, and dentists/oral surgeons should be sensitized to this fact.
Most patients who complain of TMJ/TMD pain have a myofascial component. These patients have pain associated with the masticatory muscles, which can become highly inflamed, swollen, or tender because of several causes ( Fig. 2 ). An average mouth opening is 40 mm. There may be a limitation on opening because of functional inhibition to opening or because of guarding. Pain on palpation of the temporalis and masseter muscles bilaterally along with pterygoid muscles intraorally will elicit a pain response if inflamed. Check intraorally for wear facets on the dentition and to better assess whether the patient is a bruxer, which may contribute to myofascial pain. This cluster of pain conditions has a 2:1 predilection toward women. In totality, 5% of the population is affected with temporomandibular disorders.