The anticonvulsant medications can be particularly effective treatment for neuropathic pain that is described as burning and lancinating in nature. Commonly used medications in this category include phenytoin, carbamazepine, valproic acid, clonazepam and gabapentin.
Phenytoin was first used in the 1940s for the treatment of trigeminal neuralgia. Subsequently, carbamazepine was studied and has proven to be particularly effective against glossopharyngeal neuralgia, post-herpetic neuralgia, trigeminal neuralgia and diabetic neuropathies. Should carbamazepine prove ineffective, it can be replaced with phenytoin. Unlike the other anticonvulsants, valproic acid has found some success in treating migraine headaches. The combination of an anticonvulsant with a tricyclic antidepressant (TCA) can be synergistic. Oxcarbazepine is a newer, chemically related drug with a more favourable side-effect profile.
Lamotrigine also has action at sodium channels and hence may suppress the neuronal release of glutamate (amino acid involved in neuronal hyperexcitability and persisting pain).
The mechanism of action of the anticonvulsant medications is thought to involve membrane stabilisation. Evidence also suggests that some of the agents, such as carbamazepine and phenytoin, can depress both segmental and descending excitatory pathways in the central nervous system (CNS), and at the same time facilitate inhibitory mechanisms. Carbamazepine has been shown to inhibit the electrical C and A fibre-evoked neuronal responses of spinal nerve ligated rats.
Valproic acid, on the other hand, has been reported to increase gamma–amino butyric acid (GABA) levels in the substantia nigra and corpus striatum. Gabapentin, reportedly, increases extracellular GABA levels throughout the brain, including the thalamus, and causes the release of GABA from glial cells. However, it is unlikely that gabapentin increases GABAergic tone, because neither GABAa nor GABAb antagonists reverse the analgesic effects of gabapentin.
Because of the significant risks of blood dyscrasias and liver dysfunction, baseline and periodic monitoring of blood chemistry and liver function tests are highly recommended when prescribing phenytoin, carbamazepine or valproic acid.
Although clonazepam, a benzodiazepine, is usually used for the treatment of petit mal and myoclonic seizures, it has been successfully utilised to treat the lancinating pain associated with phantom limb pain. Its mechanism of action may be associated with its reputed ability to enhance the inhibitory action of GABA within the CNS, and also possibly secondary to increased serotonin levels.