Persistent Idiopathic Facial Pain 

Updated: Nov 16, 2021
Author: Stanley J Krolczyk, DO, RPh; Chief Editor: Robert A Egan, MD 

Overview

Practice Essentials

Persistent idiopathic facial pain (PIFP), originally known as atypical facial pain, refers to pain along the territory of the trigeminal nerve that does not fit the classic presentation of other cranial neuralgias.[1, 2] The pain is usually of long duration, lasting most of the day (if not continuous), is unilateral, and is without autonomic signs or symptoms. It is described as a severe ache, crushing sensation, or burning sensation.

Signs and symptoms

The Headache Classification Subcommittee of the International Headache Society defines PIFP as follows:[3] ​

  • Pain is in the face

  • Pain is present daily and persists for all or most of the day

  • Pain is confined at onset to a limited area on one side of the face and is deep and poorly localized

  • In addition, the pain is not associated with sensory loss or other physical signs, with no abnormalities in laboratory or imaging studies

Diagnosis

PIFP is a diagnosis of exclusion. 

Diagnostic imaging may be helpful. Magnetic resonance imaging (MRI) of the brain, with and without gadolinium contrast, is the modality of choice in this setting. Computed tomography (CT) of the brain with contrast has a lower yield than MRI does because it yields poorer resolution of the posterior fossa and cranial nerves.

Management

Medical treatment of PIFP is usually less satisfactory than medical treatment of other facial pain syndromes.

Anticonvulsants (antiepileptic drugs [AEDs]) and antidepressants (eg, tricyclic antidepressants [TCAs], selective serotonin reuptake inhibitors [SSRIs], and norepinephrine reuptake inhibitors [NeRIs]) are the mainstays of pharmacologic treatment. Narcotics may be appropriate if administered under careful supervision.

Background

Persistent idiopathic facial pain (PIFP), originally known as atypical facial pain, refers to pain along the territory of the trigeminal nerve that does not fit the classic presentation of other cranial neuralgias.[1, 2] The pain is usually of long duration, lasting most of the day (if not continuous), is unilateral, and is without autonomic signs or symptoms. It is described as a severe ache, crushing sensation, or burning sensation. Upon examination and workup, no abnormality is noted.

Within the group of chronic facial pain syndromes, PIFP represents a particular diagnostic challenge. Patients frequently are misdiagnosed or attribute their pain to a prior event, such as a dental procedure or facial trauma. Psychiatric symptoms of depression and anxiety are prevalent in this population, further compounding the diagnostic conundrum. Treatment of PIFP is typically less effective than that of other facial pain syndromes, and a multidisciplinary approach is required to address the many facets of this pain syndrome.

For patient education resources, see the Brain and Nervous System Center, as well as Trigeminal Neuralgia (Facial Nerve Pain).

Pathophysiology and Etiology

The Headache Classification Subcommittee of the International Headache Society defines persistent idiopathic facial pain (PIFP) as follows:[3]

  • Pain is in the face

  • Pain is present daily and persists for all or most of the day

  • Pain is confined at onset to a limited area on one side of the face and is deep and poorly localized

  • In addition, the pain is not associated with sensory loss or other physical signs, with no abnormalities in laboratory or imaging studies

PIFP usually does not have a specific cause; however, injury of the trigeminal nerve proximally or distally may lead to this disorder. Demyelination, either central or peripheral, may initiate PIFP symptoms. Infectious causes should also be considered.

Epidemiology and Prognosis

Because of a lack of agreement on classification criteria, accurate figures on the frequency of persistent idiopathic facial pain (PIFP) are difficult to obtain. The estimated incidence has been estimated to be 1 case per 100,000 population (0.001%), though this number may be an underestimate.[4] A German study that included 3336 participants estimated the lifetime prevalence of PIFP to be 0.03%.[5]

PIFP mainly affects adults and is rare in children.[4] Overall, the disorder affects both sexes approximately equally, but more women than men seek medical care.[4]

For patients who do not respond to the available pharmacologic and nonpharmacologic therapies, the prognosis is poor.

 

Presentation

History

Persistent idiopathic facial pain (PIFP) is essentially a diagnosis of exclusion. Daily or near-daily headaches are a widespread problem in clinical practice.[1, 4] According to population-based data from the United States, Europe, and Asia, chronic daily headache affects a large number of patients (approximately 4-5% of the population).[4, 6, 7]

A careful history and physical examination, including a dental consultation, laboratory studies, and imaging studies, may be necessary to rule out occult pathology. Underlying pathology such as malignancy, vasculitis, infection, and central or peripheral demyelination may manifest early as neuralgia, and not until focal neurologic deficits, imaging abnormalities, or laboratory abnormalities are discovered does the diagnosis become evident. Rare cases of referred pain must also be considered.

It is important to distinguish PIFP from other chronic daily headache syndromes, including the following:[4, 6, 7, 8, 9, 10]

  • Trigeminal neuralgia

  • Postherpetic neuralgia

  • Temporomandibular joint (TMJ) syndrome

  • Chronic cluster headache

  • Cluster-tic syndrome

  • SUNCT (s hort-lasting, u nilateral, n euralgiform headache attacks with c onjunctival injection and t earing) syndrome

  • Jabs and jolts syndrome

  • Raeder syndrome

  • Thalamic pain syndrome

  • Hemicrania continua

  • Side-locked migraine

The following are characteristic of other chronic facial pain syndromes from which PIFP should be differentiated.

Clinical features distinguishing other chronic facial pain syndromes from PIFP

Trigeminal neuralgia

Trigeminal neuralgia is characterized by severe bursts of lancinating pain in 1 or more branches of the trigeminal nerve. Bursts are quick, repetitive, electric shock–like sensations. Each pain episode is seconds in duration, occurs irregularly, and is not related to the patient’s pulse. Treatments include antiepileptic drugs (AEDs), antidepressants (eg, tricyclic antidepressants [TCAs], selective serotonin reuptake inhibitors [SSRIs], and norepinephrine reuptake inhibitors [NeRIs]), injections, and surgical intervention.[11, 12]

Postherpetic neuralgia

Postherpetic neuralgia is defined as pain that persists for 1-6 months after an acute herpes zoster infection. The pain is neuropathic in nature. It is associated with allodynia and hyperalgesia, most commonly affecting the V1 distribution of the trigeminal nerve. The mainstays of treatment are AEDs, TCAs, and SSRIs.[13]

Temporomandibular joint syndrome

TMJ syndrome is characterized by focal tenderness to one or both TMJs and is usually aggravated by chewing, talking, and jaw movement. The quality of the pain is similar to that of PIFP (ie, dull, aching, crushing, or burning). Treatment of TMJ syndrome is often directed either at the articular joint itself or at fatigue of the periodontal ligament and the temporalis.

Cluster headache

Cluster headache is characterized by the sudden onset of severe, boring, and burning pain. Episodes last 30-180 minutes. The pain awakens the patient from sleep and does not improve with rest. Many individuals pace, and some may even injure themselves because of the severity of the pain. Associated symptoms include ipsilateral conjunctival injection, tearing, and nasal congestion. The male-to-female ratio is 6:1.

Abortive treatment includes oxygen (8-15 L), sumatriptan injections, dihydroergotamine, or combinations thereof. Preventive treatment includes verapamil, lithium, divalproex sodium, and topiramate.[14]

Cluster-tic syndrome

Cluster-tic syndrome is a difficult diagnosis and is easily confused with other facial pain syndromes. The 3 types of pain include pain with clusterlike features, pain with trigeminal neuralgia features, and a combination of these 2 types. Treatment includes AEDs, TCAs, and SSRIs or NeRIs.[15]

SUNCT syndrome

SUNCT syndrome may be a variation of the cluster-tic syndrome. It is characterized by brief (15-120 seconds) bursts of pain in the eyes, temple, or face. The pain is usually unilateral and is described as burning, stabbing, or electric. It occurs frequently (>100 episodes) in a 24-hour period. Neck movements can trigger the pain. SUNCT syndrome is refractory to medical therapy.[16]

Jabs and jolts syndrome, primary stabbing headache, or icepick headache

In this setting, head pain occurs as a single stab or a series of stabs. The pain is exclusive to or predominantly felt in the distribution of V1. Stabs last for up to a few seconds and recur with an irregular frequency that ranges from once daily to many times a day. No other accompanying symptoms are noted, and the pain cannot be attributed to another disorder. This syndrome is refractory to medical treatment.[17]

Raeder syndrome

Raeder syndrome is characterized by a V1 distribution of a unilateral burning facial pain associated with hyperesthesia, ptosis, and miosis. The pain may be caused by trauma, a middle cranial fossa mass lesion, syphilis, or sinusitis. In the absence of these underlying conditions, the pain is self-limited.[18]

Thalamic pain syndrome

Thalamic pain syndrome is described as unilateral facial pain and dysesthesias and is attributed to a lesion of the ventral-medial thalamic nuclei. It is typically a severe, burning, or aching pain localized to the contralateral side of the face. The diagnosis can be made by means of imaging studies or can be based on the presence of other associated symptoms in the trunk or limbs.

Hemicrania continua

The rare condition known as hemicrania continua is characterized by unilateral headache and facial pain. The daily head pain is continuous (24 h/d, 7 d/wk), with pain exacerbation periods that occur with variable frequency (from multiple times per week to every third month or even less often). The pain at baseline is mild to moderate, and exacerbations are moderate to severe in intensity. It is associated with migraine or cluster features (eg, photophobia, nausea, aura, lacrimation, eye injection).

Hemicrania continua responds to indomethacin, and this response facilitates diagnosis.[14, 19, 20] Abortive treatment includes oxygen (8-15 L), sumatriptan injections, and dihydroergotamine. Preventive treatment includes verapamil, lithium, divalproex sodium, and topiramate.[14]

Migraine

Migraine is a common condition. The female-to-male ratio is 3:1. It is commonly unilateral but can be bilateral. The pain has a throbbing quality and feels as if it is associated with a pulse. Photophobia, phonophobia, and osmophobia are typical features, as is nausea. The pain worsens with exertion and improves with sleep. The patient may or may not experience aura.

Pharmacologic therapy includes abortive and preventive medications, depending on the frequency and severity of the headaches. Abortive agents include serotonin agonists, ergotamine, isometheptene, and anti-inflammatory drugs. Preventive agents include AEDs, beta-blockers, calcium channel blockers, TCAs, SSRIs or NeRIs, and angiotensin-receptor blockers.

Physical Examination

As indicated by the definition of persistent idiopathic facial pain (PIFP), the findings from the general physical examination and the neurologic examination should be normal.

Pain evoked responses after stimulation are less common with PIFP than with trigeminal neuralgia. Palpation- and manipulation-induced tenderness of the TMJ is associated more closely with TMJ syndrome and less so with other cephalalgias or facial pain syndromes.

 

DDx

Diagnostic Considerations

In addition to the conditions listed in the differential diagnosis, other problems to be considered include the following:

  • Brainstem syndromes

  • Chronic pain programs

  • Demyelinating disease, either peripheral or central

  • Malignant and nonmalignant pain syndromes

  • Temporomandibular joint (TMJ) syndrome

Differential Diagnoses

 

Workup

Approach Considerations

Persistent idiopathic facial pain (PIFP) is a diagnosis of exclusion. All other causes of facial pain (see Presentation) must be excluded (especially those amenable to surgical treatment).

Diagnostic imaging may be helpful. Magnetic resonance imaging (MRI) of the brain, with and without gadolinium contrast, is the modality of choice in this setting. Computed tomography (CT) of the brain with contrast has a lower yield than MRI does because it yields poorer resolution of the posterior fossa and cranial nerves.

 

Treatment

Approach Considerations

Medical treatment of persistent idiopathic facial pain (PIFP) is usually less satisfactory than medical treatment of other facial pain syndromes. Pharmacotherapeutic knowledge is paramount in the treatment of this refractory pain syndrome. A multimechanistic approach, using modulation of both ascending and descending pain pathways, is frequently necessary. The goal of therapy is to manage the pain effectively while giving rise to the fewest possible adverse medication effects.

Anticonvulsants (antiepileptic drugs [AEDs]) and antidepressants (eg, tricyclic antidepressants [TCAs], selective serotonin reuptake inhibitors [SSRIs], and norepinephrine reuptake inhibitors [NeRIs]) are the mainstays of pharmacologic treatment. Narcotics may be appropriate if administered under careful supervision.

Pharmacologic Therapy

Medications used to treat persistent idiopathic facial pain (PIFP) include the following:

  • Antidepressants

  • Anticonvulsants

  • Substance P depletion agents

  • Topical anesthetics

  • N -methyl-D-aspartate (NMDA) antagonists

  • Tetrahydrocannabinol (THC) or cannabidiol (CBD) receptor agonists

  • Opiate medications

Of these classes of medications, anticonvulsants and antidepressants appear to be the most effective.[21] The neuropathic component of the pain responds well to anticonvulsants and antidepressants.

Surgical, Psychiatric, and Alternative Treatments

Details of neurosurgical interventions to treat persistent idiopathic facial pain (PIFP) are beyond the scope of this review. If analgesic surgery is under consideration, it should be performed at a center well versed in such procedures. Occipital nerve block, though useful for treating several craniofacial neuralgias, does not appear to be especially effective against PIFP.[22, 23]

Psychiatric treatment is important in the overall management of a patient with chronic pain.

The results of a small study from Taiwan suggest that low-energy (eg, 800-nm wavelength) diode laser therapy may prove to be a useful alternative treatment for PIFP.[24]

Alternative therapies such as acupuncture and neuromuscular reeducation have been tried and should be considered as part of a comprehensive treatment plan. Available data on alternative treatments are limited.[25, 26]

Consultations

Psychometric testing may be of benefit in the evaluation and treatment of patients with headache and facial pain. Many tests have been applied, but probably the most widely used is the Minnesota Multiple Personality Inventory (MMPI). Although psychometric testing is especially useful in the evaluation of the chronic headache and facial pain patients, a thorough discussion of such testing is beyond the scope of this discussion and is mentioned here only for completeness.

Consultation with a dentist may be of benefit.

All treatments should be provided in cooperation with the patient’s primary care physician.

 

Medication

Medication Summary

The goal of therapy is to manage the persistent facial pain with anticonvulsants and antidepressants. Narcotics may be appropriate if administered under careful supervision.

Antidepressants, TCAs

Class Summary

Tricyclic antidepressants (TCAs) are a complex group of drugs that have central and peripheral anticholinergic effects and sedative effects. They block the active reuptake of norepinephrine and serotonin.

Amitriptyline

Amitriptyline increases the synaptic concentration of serotonin or norepinephrine in the central nervous system (CNS) by inhibiting their reuptake by the presynaptic neuronal membrane. It is useful as an analgesic for certain types of chronic and neuropathic pain.

Nortriptyline (Pamelor)

Nortriptyline has demonstrated effectiveness in the treatment of chronic pain. It increases the synaptic concentration of serotonin or norepinephrine in the CNS by inhibiting their reuptake by the presynaptic neuronal membrane. Additional pharmacodynamic effects, such as desensitization of adenyl cyclase and downregulation of beta-adrenergic receptors and serotonin receptors, appear to play roles.

Duloxetine (Cymbalta)

Duloxetine is approved by the US Food and Drug Administration (FDA) for diabetic peripheral neuropathic pain. It is a potent inhibitor of neuronal serotonin and norepinephrine reuptake.

Anticonvulsants

Class Summary

Although anticonvulsants are useful for neuropathic pain, their mechanism of action in this setting is unknown.

Carbamazepine (Tegretol, Carbatrol, Epitol)

Carbamazepine has antineuralgic effects. It may depress the activity of the nucleus ventralis of the thalamus or may decrease synaptic transmission or summation of temporal stimulation, thus leading to neural discharge by limiting the influx of sodium ions across the cell membrane or through other unknown mechanisms. The target blood serum concentration range is 4-12 mg/L.

Pregabalin (Lyrica)

Pregabalin is FDA-approved for use in postherpetic neuralgia and painful diabetic peripheral neuropathy. Compared with placebo, it brings about a statistically significant reduction in mean pain score and pain-related sleep interference.

Pregabalin binds with high affinity to the alpha2-delta subunit of voltage-gaited calcium channels, thereby reducing excitatory neurotransmitters. It has a half-life of about 6 hours and is eliminated via renal excretion. A decrease in creatinine clearance results in decreased elimination and, therefore, a higher plasma concentration. Peak plasma concentration occurs at 1 and 1.5 hours after oral intake. Bioavailability is 90%. After repeated dosing, steady-state concentration is achieved at 24-48 hours. The drug can be taken with or without food.

Gabapentin (Neurontin, Gralise)

Gabapentin has properties common to other anticonvulsants and exerts antineuralgic effects. Its exact mechanism of action is not known. Gabapentin is structurally related to gamma-aminobutyric acid (GABA) but does not interact with GABA receptors. It has efficacy at the alpha2-delta subunit.

Phenytoin (Dilantin, Phenytek)

Phenytoin may stabilize neuronal membranes and treat neuralgia by increasing efflux or decreasing influx of sodium ions across cell membranes in the motor cortex during generation of nerve impulses. When the serum level is in or near the therapeutic range, adjust the dose in 30- to 50-mg increments. Small increments may cause greater than expected increases in serum concentration (ie, Michaelis-Menten drug kinetics). Because half-life is concentration-dependent, steady-state serum levels may take as long as 3 weeks to develop.

Lamotrigine (Lamictal)

Lamotrigine is a triazine derivative that is useful in the treatment of neuralgia. It inhibits the release of glutamate and inhibits voltage-sensitive sodium channels (thus stabilizing the neuronal membrane). For dose adjustments, follow the manufacturer's recommendations.

Topiramate (Topamax)

Topiramate's precise mechanism of action is unknown, but the following properties may contribute to its efficacy:

• Blockage of voltage-dependent sodium channels, as demonstrated by electrophysiologic and biochemical evidence

• Augmentation of GABA activity at some GABA-A receptor subtypes

• Antagonism of the AMPA/kainate subtype of the glutamate receptor

• Inhibition of carbonic anhydrase, particularly isozymes II and IV

Valproic acid (Depacon, Depakene, Stavzor)

The activity of valproic acid may be related to increased brain levels of GABA or enhanced GABA action.

Divalproex sodium (Depakote, Depakote ER)

The activity of divalproex sodium may be related to increased brain levels of GABA or enhanced GABA action.

Anesthetics, Topical

Class Summary

Analgesics may aid in decreasing the severity of pain.

Lidocaine anesthetic (Topicaine, Lido Patch, Lidoderm 5% patch)

Several studies support topical administration of lidocaine as treatment of postherpetic neuralgia. In a placebo-controlled study, lidocaine gel (5%) yielded significant relief in 23 patients studied. Lidocaine tape also decreases the severity of pain.

Capsaicin topical (Dolorac, Capsin, Zostrix)

Capsaicin is a natural chemical derived from plants of the Solanaceae family. By depleting and preventing reaccumulation of substance P in peripheral sensory neurons, capsaicin may render treated areas insensitive to pain. Substance P is thought to be a chemomediator of pain transmission from the periphery to the CNS.

Antiemetic Agents

Class Summary

Drugs of the cannabinoid class may aid in reducing neuropathic pain.

Dronabinol

Dronabinol is an orally active cannabinoid receptor agonist with complex effects on the CNS, including central sympathomimetic activity. Cannabinoid receptors have been discovered in neural tissues. These receptors play a role in mediating the effects of dronabinol and other cannabinoids. Dronabinol undergoes extensive first-pass hepatic metabolism by microsomal hydroxylation, yielding both active and inactive metabolites. It has also been shown to be highly plasma protein bound.

Several studies have shown dronabinol to have modest effects in treating neuropathic pain and muscle spasticity in individuals with demyelinating disease states.

 

Questions & Answers

Overview

What is persistent idiopathic facial pain (PIFP)?

How is persistent idiopathic facial pain (PIFP) defined?

What is the prevalence of persistent idiopathic facial pain (PIFP)?

Which patient groups have the highest prevalence of persistent idiopathic facial pain (PIFP)?

What is the prognosis of persistent idiopathic facial pain (PIFP)?

Presentation

What is the focus of clinical history to evaluate for persistent idiopathic facial pain (PIFP)?

How is persistent idiopathic facial pain (PIFP) differentiated from trigeminal neuralgia?

How is persistent idiopathic facial pain (PIFP) differentiated from postherpetic neuralgia?

How is persistent idiopathic facial pain (PIFP) differentiated from temporomandibular joint (TMJ) syndrome?

How is persistent idiopathic facial pain (PIFP) differentiated from cluster headache?

How is persistent idiopathic facial pain (PIFP) differentiated from cluster-tic syndrome?

How is persistent idiopathic facial pain (PIFP) differentiated from SUNCT syndrome?

How is persistent idiopathic facial pain (PIFP) differentiated from icepick headache?

How is persistent idiopathic facial pain (PIFP) differentiated from Raeder syndrome?

How is persistent idiopathic facial pain (PIFP) differentiated from thalamic pain syndrome?

How is persistent idiopathic facial pain (PIFP) differentiated from hemicrania continua?

How is persistent idiopathic facial pain (PIFP) differentiated from migraine?

Which physical findings are characteristic of persistent idiopathic facial pain (PIFP)?

DDX

Which conditions are included in the differential diagnoses of persistent idiopathic facial pain (PIFP)?

What are the differential diagnoses for Persistent Idiopathic Facial Pain?

Workup

How is persistent idiopathic facial pain (PIFP) diagnosed?

Treatment

How is persistent idiopathic facial pain (PIFP) treated?

Which medications are used in the treatment of persistent idiopathic facial pain (PIFP)?

What is the role of neurosurgery in the treatment of persistent idiopathic facial pain (PIFP)?

How is pain managed in persistent idiopathic facial pain (PIFP)?

What is the role of acupuncture and neuromuscular reeducation in the treatment of persistent idiopathic facial pain (PIFP)?

Which specialist consultations are beneficial to patients with persistent idiopathic facial pain (PIFP)?

Medications

What is the role of medications in the treatment of persistent idiopathic facial pain (PIFP)?

Which medications in the drug class Antiemetic Agents are used in the treatment of Persistent Idiopathic Facial Pain?

Which medications in the drug class Anesthetics, Topical are used in the treatment of Persistent Idiopathic Facial Pain?

Which medications in the drug class Anticonvulsants are used in the treatment of Persistent Idiopathic Facial Pain?

Which medications in the drug class Antidepressants, TCAs are used in the treatment of Persistent Idiopathic Facial Pain?