Neuropathic pain is defined as pain due to dysfunction of the
nervous system in the absence of ongoing tissue damage.13 The
pain typically is characterized as sharp, shooting, or burning,
and is usually felt in the area of sensory deficit. It is typically
worsened by mild stimuli that normally would not produce pain, such
as light touch or cool air. The pain tends to be chronic and causes considerable
patient discomfort. These symptoms have led to various hypotheses
about the pathophysiologic mechanisms of neuropathic pain with relevance
to AEDs.14 When peripheral nerves become damaged,
axons grow toward the formerly innervated area directed by an intact
connective tissue sheath. If this sheath is also damaged, then axon
extensions grow without any direction and become tangled into a
structure called a neuroma. Neuromas can generate ectopic electrical impulses
at the regenerating tips in the damaged primary nociceptive afferents
at various levels in the nervous system, from the dorsal root ganglia
to demyelinated regions of a root or nerve.15 Since
nerves have been damaged, there is a potential disruption in the
balance of the excitatory (e.g., glutamate) and inhibitory (e.g., γ-aminobutyric
acid, GABA) neurotransmitters. This disruption leads to hyperexcitability
of the neuronal membrane sodium channels and voltage-dependent calcium
channels, causing rapid ectopic firing. The AEDs have varying mechanisms
of action, many of which are directed at sodium and calcium-dependent
channels and GABA metabolism.