A lack of inhibition, particularly that mediated by gamma-amino
butyric acid (
GABA), the main inhibitory transmitter of the central nervous system (CNS), is responsible for many
pain states. Until recently, few
GABA acting drugs were available and were prescribed mostly for relieving
muscle spasms, anxiety and
epilepsy, but rarely for
pain. The basic metabolic pathway of
GABA is well known and we are now beginning to understand the function of this
neurotransmitter in the complex circuitry underlying
pain, especially in the context of nerve injury.
Analgesic compounds are now being developed targeting
GABA transporters as well as
GABA associated
enzymes and receptors. Some
GABA analogs act by inhibiting
ion channels, a property that contributes to their
analgesic effects. However, despite considerable progress in developing new compounds, the use of systemically acting GABAergic drugs is limited by unwanted side-effects on systems other than those involved in
pain, and by the fact that in certain areas of the brain,
GABA can enhance rather than reduce
pain. The advent of new drugs targeting subtypes of
GABA receptors and transporters and the possibility of using newly developed delivery systems, such as intrathecal pumps and viral vectors, to target specific areas of the nervous system will likely help circumvent these problems.