The Role of Glutamate Transporters in Chronic Pain

Abstract

Glutamate is the major excitatory neurotransmitter and plays important roles in the physiology of the mammalian central nervous system. In spite of its importance as a neurotransmitter, too much glutamate is toxic to neurons. Removal of glutamate from the extracellular space, which is critical for keeping the extracellular glutamate concentration below toxic level, is mediated by glutamate transporter GLT1（EAAT2）, which are primarily expressed by astrocytes. Rare loss-of-function variants and down-regulation of GLT1 have been reported in various kinds of chronic pain including neuropathic pain and migraine. In this article, I demonstrate the contributions of spinal and supraspinal GLT1 to chronic pain. In addition, I review recent advances in the generation of gene-modified mice by genome editing.