Glutamate Kainate Receptor in Pain Transmission and Modulation

Abstract

Glutamate is the major excitatory transmitter in the spinal cord dorsal horn. At postsynaptic sites, subtypes of glutamate receptors are important for mediating sensory synaptic responses. While AMPA and NMDA receptors are likely expressed in all sensory synapses, kainate(KA) receptors are expressed mainly in synapses receiving high-threshold sensory inputs. In addition to its postsynaptic role, presynaptic KA receptors are important for regulation of both excitatory and inhibitory transmission within the dorsal horn. In the spinal cord dorsal horn, excitatory sensory fibers often terminate adjacent to sites of GABA and glycine release. Glutamate released from sensory fibers caused a KA and GABAB receptor-dependent suppression of inhibitory transmission in spinal slices, providing evidence for a new role of KA receptors in regulating sensory transmission. Genetic studies using selective KA subtype receptor knockout mice found that KA receptors are important for persistent inflammatory pain as well as emotional responses to pain.