Extrasynaptic AMPA receptors in the dorsal horn: Evidence and functional significance

Extrasynaptic AMPA receptors (AMPARs) are widely expressed in the brain, spinal cord and periphery. These receptors are critically involved in activity-dependent synaptic transmission and changes in their functioning are causally linked to multiple neuropathologies in the central nervous system (CNS). However, most studies in this field have been concentrated on elucidating synaptic AMPAR functioning, leaving a possible involvement of an extrasynaptic pool of AMPARs in normal and pathological signaling open for consideration.Here, we review the present evidence for extrasynaptic AMPAR function in the dorsal horn neurons of the spinal cord, linking these receptors to neurotransmission and non-synaptic signaling in this part of the CNS. In addition, we summarize current knowledge about the role of extrasynaptic AMPARs in the development and maintenance of pain states during inflammation. This knowledge potentially suggests the development of alternative therapies to prevent and/or treat inflammatory pain.

► Structure of AMPA receptors and subunit expression in dorsal horn is reviewed.
► Properties of extrasynaptic AMPARs in dorsal horn neurons are described.
► Impact of extrasynaptic AMPARs to glutamatergic transmission in dorsal horn is summarized.
► Role of dorsal horn extrasynaptic AMPARs in inflammatory pain is discussed.