Persistent Idiopathic Facial Pain Medication
- Author: Stanley J Krolczyk, DO, RPh; Chief Editor: Robert A Egan, MD more...
The goal of therapy is to manage the persistent facial pain with anticonvulsants and antidepressants. Narcotics may be appropriate if administered under careful supervision.
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 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 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 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.
Although anticonvulsants are useful for neuropathic pain, their mechanism of action in this setting is unknown.
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 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 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 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 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'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
The activity of valproic acid may be related to increased brain levels of GABA or enhanced GABA action.
The activity of divalproex sodium may be related to increased brain levels of GABA or enhanced GABA action.
Analgesics may aid in decreasing the severity of pain.
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 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.
Drugs of the cannabinoid class may aid in reducing neuropathic pain.
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.
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