Neuropathic pain: drug targets for current and future interventions

Nociceptive pain alerts the body to potential or actual tissue damage. By contrast, neuropathic pain, which results from injury or damage to the nervous system, persists long after all signs of the original injury have disappeared. This type of maladaptive pain presents a significant clinical problem, as it responds poorly or unpredictably to classical analgesics. There is also no single, uniformly well-tolerated drug that is reliably helpful. Current understanding of the etiology of neuropathic pain reveals seven potential targets for therapeutic intervention. These are: 1) ectopic activity in damaged peripheral nerves; 2) increased excitability in spinal dorsal horn neurons; 3) restoration or augmentation of GABAergic inhibition in the dorsal horn; 4) supraspinal and affective mechanisms; 5) alterations in the sympathetic nervous system; 6) spinal peptidergic mechanisms; and 7) spinal excitatory amino acid receptors. Current therapeutic approaches, using drugs such as gabapentin, anticonvulsants, ketamine or methadone, and potential new approaches are discussed in the context of these seven drug targets.