Journal
PHARMACOLOGICAL RESEARCH
Volume 185, Issue -, Pages -Publisher
ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
DOI: 10.1016/j.phrs.2022.106492
Keywords
Allosteric modulation; Astrocytes; EAAT2; GLT-1; Glia; Glutamate; Glutamate transporters; Neuropathic pain; Non-opioid therapies; Sex differences
Categories
Funding
- AANA Foundation Grant [2022-G-5]
- NINDS [NS111767]
- NIDA [DA047700]
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Neuropathic pain is a common disease that lacks effective pharmacotherapies. Modulating glutamate transporters may be a novel approach to treating pain. This review summarizes the physiology of the glutamatergic system, preclinical evidence in animal models, and emerging therapies that modulate glutamate transport in neuropathic pain.
Neuropathic pain, a disease of the somatosensory nervous system, afflicts many individuals and adequate management with current pharmacotherapies remains elusive. The glutamatergic system of neurons, receptors and transporters are intimately involved in pain but, to date, there have been few drugs developed that therapeutically modulate this system. Glutamate transporters, or excitatory amino acid transporters (EAATs), remove excess glutamate around pain transmitting neurons to decrease nociception suggesting that the modulation of glutamate transporters may represent a novel approach to the treatment of pain. This review highlights and summarizes (1) the physiology of the glutamatergic system in neuropathic pain, (2) the preclinical evidence for dysregulation of glutamate transport in animal pain models, and (3) emerging novel therapies that modulate glutamate transporters. Successful drug discovery requires continuous focus on basic and translational methods to fully elucidate the etiologies of this disease to enable the development of targeted therapies. Increasing the efficacy of astrocytic EAATs may serve as a new way to successfully treat those suffering from this devastating disease.
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