You are in: eMedicine Specialties > Neurology > Headache and Pain Persistent Idiopathic Facial PainArticle Last Updated: Mar 15, 2007AUTHOR AND EDITOR INFORMATIONSection 1 of 10
  Author: Stanley J Krolczyk, DO, RPh, Assistant Professor, Department of Neurology, University of South Florida College of Medicine Stanley J Krolczyk is a member of the following medical societies: American Academy of Neurology, American Headache Society, American Medical Association, and American Osteopathic Association Coauthor(s): Maria-Carmen B Wilson, MD, Medical Director of Pain Management, Department of Neurology, Tampa General Hospital; Associate Professor, Department of Neurology, Assistant Professor, Department of Pediatrics, University of South Florida College of Medicine; Lourdes Benes-Cases, MD, Resident, Department of Neurology, Tampa General Hospital; Shirley Chen, DO, Resident, Department of Neurology, Tampa General Hospital; Angel R Gonzalez-Rodriguez, MD, Resident, Department of Neurology, Tampa General Hospital Editors: Joseph R Carcione, Jr, DO, MBA, Consultant in Neurology and Medical Acupuncture, Medical Management and Organizational Consulting, Central Westchester Neuromuscular Care, PC; Medical Director, Oxford Health Plans; Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine; Robert A Egan, MD, Director of Neuro-Ophthalmology, St Helena Hospital; Selim R Benbadis, MD, Professor, Director of Comprehensive Epilepsy Program, Departments of Neurology and Neurosurgery, University of South Florida School of Medicine, Tampa General Hospital; Nicholas Y Lorenzo, MD, Chief Editor, eMedicine Neurology; Consulting Staff, Neurology Specialists and Consultants Author and Editor Disclosure Synonyms and related keywords: trigeminal nerve, trigeminal neuralgia, TMJ, temporomandibular joint syndrome, TMJ syndrome, migraine, headache, cluster headache INTRODUCTIONSection 2 of 10
  BackgroundThe term atypical facial pain was first introduced by Frazier and Russell in 1924. It has since been renamed persistent idiopathic facial pain (PIFP). PIFP refers to pain along the territory of the trigeminal nerve that does not fit the classic presentation of other cranial neuralgias (Pascual, 2001). The duration of pain is usually long, lasting most of the day (if not continuous). Pain is unilateral and 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. The International Headache Society defines PIFP as follows (Headache Classification Subcommittee of the International Headache Society, 2004):
Within the group of chronic facial pain syndromes, PIFP represents a 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 and compound the diagnostic conundrum. Treatment is less effective than in other facial pain syndromes and requires a multidisciplinary approach to address the many facets of this pain syndrome. FrequencyUnited StatesAccurate figures are difficult to obtain because of the lack of agreement on classification criteria. Estimated incidence is 1 case per 100,000 population, although this number may be underestimated (Kavuk, 2003). SexPIFP affects both sexes approximately equally, but more women than men seek medical care (Kavuk, 2003). AgeThe disorder mainly affects adults and is rare in children (Kavuk, 2003). CLINICALSection 3 of 10
HistoryPIFP is essentially a diagnosis of exclusion. Daily or near-daily headaches are a widespread problem in clinical practice (Pascual, 2001; Kavuk, 2003). According to population-based data from the United States, Europe, and Asia, chronic daily headache affects a large number (approximately 4-5% of the population) of patients (Kavuk, 2003; Bordini, 1991; Madland, 2001). Importantly, PIFP must be distinguished from various other chronic daily headache syndromes, including hemicrania continua (Kavuk, 2003; Bordini, 1991), temporomandibular joint (TMJ) syndrome, side-locked migraine, chronic cluster headache, SUNCT (short-lasting, unilateral, neuralgiform headache attacks with conjunctival injection and tearing) syndrome, trigeminal neuralgia, and many others (Madland, 2001; Volcy, 2006; Kaup, 2003; Leone, 1993). 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. The following are examples of common facial pain or headache syndromes, along with some of the classic characteristics:
PhysicalNeurological and physical examination findings, by definition of PIFP, should be normal. Pain evoked responses after stimulation are less common than with trigeminal neuralgia. Palpation- and manipulation-induced tenderness of the TMJ is associated with TMJ syndrome and less so with other cephalgias or facial pain syndromes. CausesPIFP 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, also may initiate PIFP symptoms. DIFFERENTIALSSection 4 of 10
Brainstem Gliomas Chronic Paroxysmal Hemicrania Cluster Headache Headache: Pediatric Perspective Migraine Headache Migraine Headache: Neuro-Ophthalmic Perspective Migraine Headache: Pediatric Perspective Migraine Variants Temporomandibular Disorders Trigeminal Neuralgia
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| Drug Name | Amitriptyline (Elavil) |
|---|---|
| Description | Increases synaptic concentration of serotonin and/or norepinephrine in CNS by inhibiting reuptake by presynaptic neuronal membrane. Useful as analgesic for certain types of chronic and neuropathic pain. |
| Adult Dose | 30-100 mg/d PO hs |
| Pediatric Dose | Children: 0.1 mg/kg PO hs; increase, as tolerated, over 2-3 wk to 0.5-2 mg/d hs Adolescents: 25-50 mg/d PO hs; increase gradually to 100 mg/d in divided doses |
| Contraindications | Documented hypersensitivity, MAOIs in past 14 d |
| Interactions | Because metabolized by P450-2D6 system, other drugs that inhibit this enzyme system (eg, cimetidine, quinidine) may increase levels; phenobarbital may increase metabolism, decreasing effects; blocks uptake of guanethidine and prevents its hypotensive effects; may interact with thyroid medications, alcohol, CNS depressants, barbiturates, and disulfiram |
| Pregnancy | D - Unsafe in pregnancy |
| Precautions | May have pronounced effects in cardiovascular system; use cautiously in elderly patients and those with cardiac conduction disturbances, history of hyperthyroidism, or renal or hepatic impairment |
| Drug Name | Nortriptyline (Aventyl hydrochloride, Pamelor) |
|---|---|
| Description | Has demonstrated effectiveness in treatment of chronic pain. Increases synaptic concentration of serotonin and/or norepinephrine in CNS by inhibiting their reuptake by presynaptic neuronal membrane. Additional pharmacodynamic effects, such as desensitization of adenyl cyclase and down-regulation of beta-adrenergic receptors and serotonin receptors, appear to play roles. |
| Adult Dose | 25 mg PO tid/qid; not to exceed 150 mg/d |
| Pediatric Dose | <25 kg: Not recommended 25-35 kg: 10-20 mg/d PO 35-54 kg: 25-35 mg/d PO |
| Contraindications | Documented hypersensitivity, narrow-angle glaucoma, MAOIs in past 14 d |
| Interactions | Cimetidine may increase levels; may increase PT in patients stabilized on warfarin |
| Pregnancy | D - Unsafe in pregnancy |
| Precautions | Use cautiously in patients with renal or hepatic impairment, cardiac conduction disturbances, or history of hyperthyroidism |
| Drug Name | Duloxetine (Cymbalta) |
|---|---|
| Description | FDA approved for diabetic peripheral neuropathic pain. Potent inhibitor of neuronal serotonin and norepinephrine reuptake. |
| Adult Dose | 60 mg PO qd; may initiate with lower dose in patient unable to tolerate 60 mg/d |
| Pediatric Dose | Not established |
| Contraindications | Documented hypersensitivity; uncontrolled narrow-angle glaucoma; do not administer within 14 d after stopping MAOI use or initiate MAOIs within 5 d after stopping duloxetine |
| Interactions | Metabolized by CYP1A2 and CYP2D6; coadministration with drugs that inhibit CYP1A2 (eg, fluvoxamine, cimetidine, ciprofloxacin, enoxacin) may increase duloxetine blood levels and toxicity; coadministration with drugs that inhibit CYP2D6 (eg, paroxetine, fluoxetine, quinidine) may increase duloxetine blood levels and toxicity; moderately inhibits CYP2D6 and may decrease elimination of CYP2D6 substrates (eg, TCAs, phenothiazines [eg, thioridazine], type 1C antiarrhythmics [eg, propafenone, flecainide]); coadministration with MAOIs may cause serious and sometimes fatal reactions that include hyperthermia, rigidity, myoclonus, autonomic instability, and mental status changes, including extreme agitation, delirium, and coma (see Contraindications) |
| Pregnancy | C - Safety for use during pregnancy has not been established. |
| Precautions | Observe closely for clinical worsening and suicidality when initiating treatment or following dosage change; gradually decrease dose when discontinuing and do not abruptly discontinue; caution with hepatic impairment or end-stage renal disease; may cause slight blood pressure increase; may activate mania or hypomania; common adverse effects include nausea, dry mouth, constipation, decreased appetite, fatigue, somnolence, and increased sweating |
Although useful, their mechanism of action in neuropathic pain is unknown.
| Drug Name | Carbamazepine (Tegretol, Carbatrol, Epitol) |
|---|---|
| Description | Has antineuralgic effects; may depress activity of nucleus ventralis of thalamus or decrease synaptic transmission or summation of temporal stimulation, leading to neural discharge by limiting influx of sodium ions across cell membrane or other unknown mechanisms. Target blood serum concentrations 4-12 mg/L. |
| Adult Dose | 200 mg PO bid initial dose; increase gradually prn over 2 wk to 200 mg tid Sustained-release form: Therapeutic dose bid |
| Pediatric Dose | <6 years: 10-20 mg/kg/d PO initial dose; titrate dose prn 6-12 years: 100 mg PO bid initial dose; titrate dose prn >12 years: 200 mg PO bid initial dose; titrate dose prn |
| Contraindications | Documented hypersensitivity, bone marrow suppression, MAOIs |
| Interactions | Serum levels may increase significantly within 30 d of danazol coadministration (avoid whenever possible); do not coadminister with MAOIs; cimetidine may increase toxicity, especially if taken in first 4 wk of therapy; may decrease primidone and phenobarbital levels (their coadministration may increase carbamazepine levels) |
| Pregnancy | C - Safety for use during pregnancy has not been established. |
| Precautions | Discontinue MAOIs for minimum of 14 d before starting carbamazepine; use cautiously in patients with history of cardiac damage or hepatic disease; blood cell abnormalities have been reported following this medication; may worsen primary generalized epilepsy or atypical absence seizures; 0.5-1% risk of spina bifida in children born to mothers who take carbamazepine during pregnancy |
| Drug Name | Pregabalin (Lyrica) |
|---|---|
| Description | FDA approved for use in postherpetic neuralgia and painful diabetic peripheral neuropathy. Freynhagen et al describe statistically significant reduction in mean pain score and pain-related sleep interference compared with placebo. Binds with high affinity to alpha2-delta subunit of voltage-gaited calcium channels, thereby reducing excitatory neurotransmitters. Has half-life of approximately 6 h and is eliminated by renal excretion. Decrease in CrCl results in decreased elimination and, therefore, increase in plasma concentration. Peak plasma concentration occurs at 1 and 1.5 h after oral intake. Bioavailability is 90%. Following repeated dosing, steady-state concentration is achieved at 24-48 h. Can be taken with or without food. |
| Adult Dose | 75 mg PO bid initially; may increase to 150 mg bid in 1 wk; may increase to 300 mg bid if needed and tolerated |
| Pediatric Dose | Not established |
| Contraindications | Documented hypersensitivity |
| Interactions | May cause additive effects on cognitive and gross motor functioning when coadministered with drugs that cause dizziness or somnolence; antacids can reduce bioavailability by 20%; cimetidine may decrease clearance; may increase levels of norethindrone |
| Pregnancy | C - Safety for use during pregnancy has not been established. |
| Precautions | Discontinue gradually (over a minimum of 1 wk) to minimize increased seizure frequency in patients with seizure disorders; may cause insomnia, nausea, headache, or diarrhea with abrupt withdrawal; common adverse effects include dizziness, somnolence, blurred vision, weight gain, and peripheral edema; may elevate creatinine kinase level, decrease platelet count, and increase PR interval; doses >300 mg/d associated with higher rate of adverse effects and treatment discontinuation; decrease dose with elderly or renal impairment (ie, CrCl <60 mL/min) |
| Drug Name | Gabapentin (Neurontin) |
|---|---|
| Description | Has properties common to other anticonvulsants and antineuralgic effects. Exact mechanism of action not known. Structurally related to GABA but does not interact with GABA receptors. Has efficacy at the alpha2-delta subunit |
| Adult Dose | 300 mg PO hs on day 1; increase to 400 mg PO tid over 3-d interval and titrate dose prn; 1800 mg/d in divided doses shows maximal efficacy |
| Pediatric Dose | <12 years: Not established >12 years: Administer as in adults |
| Contraindications | Documented hypersensitivity |
| Interactions | Antacids can reduce bioavailability by 20%; cimetidine may decrease clearance; may increase levels of norethindrone |
| Pregnancy | C - Safety for use during pregnancy has not been established. |
| Precautions | Abrupt withdrawal may precipitate seizures; use caution when treating patients with renal impairment |
| Drug Name | Phenytoin (Dilantin) |
|---|---|
| Description | May stabilize neuronal membranes and treat neuralgia by increasing efflux or decreasing influx of sodium ions across cell membranes in motor cortex during generation of nerve impulses. When serum level in or near therapeutic range, adjust dose in 30- to 50-mg increments. Small-dose increments may cause greater than expected increases in serum concentration (ie, Michaelis-Menten drug kinetics). Steady-state serum levels may take up to 3 wk to occur, because half-life is concentration dependent. |
| Adult Dose | 300 mg/d PO initial dose; adjust to maintain serum levels of 10-20 mg/L |
| Pediatric Dose | 5 mg/kg/d PO bid |
| Contraindications | Documented hypersensitivity, heart block, sinus bradycardia |
| Interactions | Rifampin, cisplatin, vinblastine, bleomycin, folic acid, theophylline, and continuous NG feedings may decrease serum levels and effects; may decrease effects of oral contraceptives, itraconazole, mebendazole, methadone, oral midazolam, valproic acid, cyclosporine, theophylline, doxycycline, quinidine, mexiletine, and disopyramide; isoniazid, chloramphenicol, or fluconazole may increase serum concentrations; may increase warfarin effects and rate of conversion of primidone to phenobarbital, resulting in increased phenobarbital serum concentrations |
| Pregnancy | D - Unsafe in pregnancy |
| Precautions | Discontinue if rash or lymphadenopathy develops; use caution in patients with hepatic dysfunction; approximately 90% protein bound (during pregnancy or low albumin states, best to adjust PO dose to maintain free serum concentrations of 1-2 mg/L) |
| Drug Name | Lamotrigine (Lamictal) |
|---|---|
| Description | Triazine derivative useful in treatment of neuralgia. Inhibits release of glutamate and inhibits voltage-sensitive sodium channels, which stabilizes neuronal membrane. Follow manufacturer's recommendation for dose adjustments. |
| Adult Dose | Monotherapy: 50-100 mg/d PO divided bid initial dose; maintenance dose of 100-400 mg/d qd or divided bid; not to exceed 500 mg/d Adjunct therapy with valproic acid: 25 mg PO qod initial dose; maintenance dose of 50-200 mg/d qd or divided bid; not to exceed 200 mg/d |
| Pediatric Dose | <2 years Not established 2-12 years Monotherapy Weeks 1-2: 0.6 mg/kg/d PO divided bid, rounded down to the nearest 5 mg Weeks 3-4: 1.2 mg/kg/d PO divided bid, rounded down to the nearest 5 mg Maintenance: 5-15 mg/kg/d PO; not to exceed 400 mg/d divided bid; to achieve usual maintenance dose, increase subsequent doses q1-2wk as follows: calculate 1.2 mg/kg/d and round down to nearest 5 mg; add this amount to previously administered daily dose Concomitant therapy with valproic acid Weeks 1-2: 0.15 mg/kg/d PO qd or divided bid, rounded down to nearest 5 mg; if initial calculated daily dose is 2.5-5 mg, then take 5 mg on alternate days for first 2 wk Weeks 3-4: 0.3 mg/kg/d PO qd or divided bid, rounded down to nearest 5 mg Maintenance: 1-5 mg/kg/d PO; not to exceed 200 mg/d qd or divided bid; to achieve usual maintenance dose, increase subsequent doses q1-2wk as follows: calculate 0.3 mg/kg/d and round down to nearest 5 mg; add this amount to previously administered qd dose >12 years Monotherapy Weeks 1-2: 50 mg/d PO Weeks 3-4: 100 mg/d PO divided bid Maintenance: 300-500 mg/d PO divided bid; to achieve maintenance, increase by 100 mg/d q1-2wk Concomitant therapy with valproic acid Weeks 1-2: 25 mg PO qod Weeks 3-4: 25 mg PO qd Maintenance: 100-400 mg/d PO qd or divided bid; to achieve maintenance, increase by 25-50 mg/d q1-2wk |
| Contraindications | Documented hypersensitivity |
| Interactions | Acetaminophen increases renal clearance, decreasing effects; phenobarbital and phenytoin increase metabolism, causing decrease in lamotrigine levels; concomitant valproic acid increases half-life of lamotrigine |
| Pregnancy | C - Safety for use during pregnancy has not been established. |
| Precautions | Use caution in patients with impaired renal or hepatic function |
| Drug Name | Topiramate (Topamax) |
|---|---|
| Description | Precise mechanism unknown, but the following properties may contribute to its efficacy: (1) electrophysiological and biochemical evidence shows blockage of voltage-dependent sodium channels, (2) augments activity of the neurotransmitter GABA at some GABA-A receptor subtypes, (3) antagonizes AMPA/kainate subtype of the glutamate receptor, and (4) inhibits the carbonic anhydrase enzyme, particularly isozymes II and IV. |
| Adult Dose | Slowly titrate upward at a minimum of 1-wk intervals as follows: Week 1: 25 mg PO qhs Week 2: 25 mg PO bid Week 3: 25 mg PO every am and 50 mg PO qhs Week 4: 50 mg PO bid |
| Pediatric Dose | Not established |
| Contraindications | Known hypersensitivity |
| Interactions | Phenytoin, carbamazepine, and valproic acid can significantly decrease levels; reduces digoxin and norethindrone levels when administered concomitantly; concomitant use with carbonic anhydrase inhibitors may increase risk of renal stone formation and should be avoided; use with extreme caution when administering concurrently with CNS depressants because may have an additive effect in CNS depression and other cognitive or neuropsychiatric adverse events |
| Pregnancy | C - Safety for use during pregnancy has not been established. |
| Precautions | Risk of developing kidney stone formation increased 2-4 times that of untreated population; risk may be reduced by increasing fluid intake; caution in renal or hepatic impairment; patients should seek immediate medical attention if they experience blurred vision or periorbital pain; continued usage after symptoms develop can lead to glaucoma; primary treatment is discontinuation; if left untreated, serious sequelae, including permanent vision loss, may occur; oligohidrosis and hyperthermia have been reported predominantly in children during vigorous exercise or exposure to warm environmental temperatures (ensure proper hydration prior to and during activity and warm temperatures) May cause hyperchloremic nonanion gap metabolic acidosis or acute or chronic metabolic acidosis resulting in hyperventilation and nonspecific symptoms (eg, fatigue, anorexia) or more severe adverse effects including cardiac arrhythmias or stupor; chronic, untreated metabolic acidosis may increase nephrolithiasis or nephrocalcinosis risk, osteomalacia (ie, rickets in pediatric patients), or osteoporosis with an increased risk for bone fractures; chronic metabolic acidosis in pediatric patients may also reduce growth rates; measure baseline and periodic serum bicarbonate Sprinkle cap should be swallowed whole, or carefully open cap and sprinkle contents on soft food immediately before ingestion; do not chew or crush |
| Drug Name | Valproic acid (Depacon, Depakote, Depakote ER) |
|---|---|
| Description | Activity may be related to increased brain levels of GABA or enhanced GABA action. |
| Adult Dose | 125-250 mg/d PO initially; titrate dose prn; not to exceed 1500 mg/d; doses >250 mg/d should be divided bid |
| Pediatric Dose | Not established |
| Contraindications | Documented hypersensitivity; hepatic disease/dysfunction; hyperammonemic encephalopathy and urea cycle disorders |
| Interactions | Coadministration with cimetidine, salicylates, felbamate, and erythromycin may increase toxicity; rifampin may significantly reduce levels; in pediatric patients, protein binding and metabolism decrease when taken concomitantly with salicylates; coadministration with carbamazepine may result in variable changes of carbamazepine concentrations with possible loss of seizure control; may increase diazepam and ethosuximide toxicity (monitor closely); may increase phenobarbital and phenytoin levels while either one may decrease valproate levels; may displace warfarin from protein-binding sites (monitor coagulation test results); may increase zidovudine levels in HIV-seropositive patients |
| Pregnancy | D - Unsafe in pregnancy |
| Precautions | Thrombocytopenia and abnormal coagulation parameters have occurred; risk of thrombocytopenia increases significantly at total trough plasma concentrations >110 mcg/mL in females and >135 mcg/mL in males; at periodic intervals and prior to surgery, determine platelet counts and bleeding time before initiating therapy; reduce dose or discontinue if hemorrhage, bruising, or a hemostasis/coagulation disorder occur; hyperammonemia may occur, resulting in hepatotoxicity; monitor patients closely for appearance of malaise, weakness, facial edema, anorexia, jaundice, and vomiting; may cause drowsiness |
May aid in decreasing severity of pain.
| Drug Name | Lidocaine (DermaFlex gel, Lidoderm 5% patch) |
|---|---|
| Description | Several recent studies have advocated topical administration of lidocaine as treatment of postherpetic neuralgia. Lidocaine gel (5%) in placebo-controlled study showed significant relief in 23 patients studied. Lidocaine tape also decreases severity of pain. |
| Adult Dose | Gel (5%): Apply to affected area prn Patch (5%): Apply to most painful area (up to 3 patches per application); patch may remain in place for up to 12 h in any 24-h period |
| Pediatric Dose | Administer as in adults |
| Contraindications | Documented hypersensitivity |
| Interactions | None reported |
| Pregnancy | B - Usually safe but benefits must outweigh the risks. |
| Precautions | For external or mucous membrane use only; do not use in eyes |
| Drug Name | Capsaicin cream (Dolorac, Capsin, Zostrix) |
|---|---|
| Description | Natural chemical derived from plants of Solanaceae family. By depleting and preventing reaccumulation of substance P in peripheral sensory neurons, may render treated areas insensitive to pain. Substance P thought to be chemomediator of pain transmission from periphery to CNS. |
| Adult Dose | Cream: Apply to skin tid/qid for 3-4 consecutive wk and evaluate efficacy; not to exceed 4 applications/d |
| Pediatric Dose | Administer as in adults |
| Contraindications | Documented hypersensitivity; do not use on areas of broken or irritated skin |
| Interactions | None reported |
| Pregnancy | C - Safety for use during pregnancy has not been established. |
| Precautions | Avoid contact with eyes; do not bandage tightly; if condition worsens or symptoms persist for 14-28 d, discontinue use and consult physician; for external use only |
Persistent Idiopathic Facial Pain excerpt
Article Last Updated: Mar 15, 2007
