NEW APPROACH TO CHRONIC PAIN THERAPY WITH DRUGS TARGETING GLUTAMATE TRANSPORTER

Abstract

Chronic visceral pain is a particularly difficult subcategory to manage. Glutamate is the most predominant excitatory
neurotransmitter and mediates many aspects of sensory function including acute and chronic pain. There is a growing
literature describing the efficacy of physiologically dominant glutamate transporter GLT-1 up-regulation in attenuating
chronic visceral and somatic nociception. Since glutamate is the major excitatory neurotransmitter released in the first
central synapse of the pain-transmitting afferent neurons, augmentation of GLT-1 activity, which reduces extracellular
levels of glutamate, may be an important target for pain management strategies. This review summarizes studies which
highlight findings that GLT-1 up-regulation by transgenic, pharmacologic and viral transfection approaches attenuates a
host of nociceptive responses emanating from visceral or somatic sources in animal models.