Spinal AMPA receptors: Amenable players in central sensitization for chronic pain therapy?

The activity-dependent trafficking of AMPA receptors (AMPAR) mediates synaptic strength and plasticity, while the perturbed trafficking of the receptors of different subunit compositions has been linked to memory impairment and to causing neuropathology. In the spinal cord, nociceptive-induced changes in AMPAR trafficking determine the central sensitization of the dorsal horn (DH): changes in AMPAR subunit composition compromise the balance between synaptic excitation and inhibition, rendering interneurons hyperexcitable to afferent inputs, and promoting Ca²⁺ influx into the DH neurons, thereby amplifying neuronal hyperexcitability. The DH circuits become over-excitable and carry out aberrant sensory processing; this causes an increase in pain sensation in central sensory pathways, giving rise to chronic pain syndrome. Current knowledge of the contribution of spinal AMPAR to the cellular mechanisms relating to chronic pain provides opportunities for developing target-based therapies for chronic pain intervention.