AMPA receptors and pain—A future therapeutic intervention?

AMPA receptors are excitatory glutamate receptors that are critical for synaptic transmission. Not surprisingly, they serve an important function at the synapse between a peripheral nociceptive neuron and a dorsal horn neuron in the spinal cord. Furthermore, a subset of AMPA receptors, calcium permeable AMPA receptors, by allowing calcium influx, is capable of activating calcium-dependent signaling pathways. The activation of these signaling pathways, in turn, leads to long-term changes at the spinal synapses and may even play a role in central sensitization. Several antagonists for AMPA receptors have been developed for preclinical studies of stroke, seizure, amyotropic lateral sclerosis, Alzheimer's disease, addiction, and pain. Many of these agents have shown promise as potential targeted therapeutic interventions for these diseases, and clinical trials are ongoing for many specific AMPA antagonists. In the near future, these AMPA antagonists may emerge as newer analgesics with fewer side effects.