Do the distinct synaptic properties of VGLUTs shape pain?

• The three VGLUT isoforms have largely distinct expression patterns and synaptic properties in the adult nervous system.
• Vesicular glutamate transporters (VGLUTs) are essential for pain transmission throughout the nervous system.
• The distinct synaptic properties of VGLUTs affect synaptic transmission and likely also pain signaling.
• They dynamic regulation of VGLUTs also affects synaptic transmission and likely pain signaling.
• Understanding the dynamic nature of synaptic transmission within pain circuits may provide new strategies to treat pain.

The somatosensory system transmits touch, temperature, itch and pain. Three vesicular glutamate transporter isoforms mediate the release of glutamate throughout the mammalian nervous system with largely non-overlapping distributions and unique roles at the synapse. This review discusses the contribution of each of these essential transporters to circuits underlying pain and other somatosensory behaviors throughout postnatal development and in the adult. A better understanding of the individual contributions of the VGLUT isoforms could provide new avenues for therapeutic intervention.