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CNS Drugs
Published in: CNS Drugs 1/2001

01-01-2001 | Review Article

Glutamate Receptors and Nociception

Implications for the Drug Treatment of Pain

Author: Dr Marian E. Fundytus

Published in: CNS Drugs | Issue 1/2001

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Abstract

Evidence from the last several decades indicates that the excitatory amino acid glutamate plays a significant role in nociceptive processing. Glutamate and glutamate receptors are located in areas of the brain, spinal cord and periphery that are involved in pain sensation and transmission. Glutamate acts at several types of receptors, including ionotropic (directly coupled to ion channels) and metabotropic (directly coupled to intracellular second messengers). Ionotropic receptors include those selectively activated by N-methyl-D-aspartate, α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid and kainate. Metabotropic glutamate receptors are classified into 3 groups based on sequence homology, signal transduction mechanisms and receptor pharmacology.
Glutamate also interacts with the opioid system, and intrathecal or systemic coadministration of glutamate receptor antagonists with opioids may enhance analgesia while reducing the development of opioid tolerance and dependence. The actions of glutamate in the brain seem to be more complex. Activation of glutamate receptors in some brain areas seems to be pronociceptive (e.g. thalamus, trigeminal nucleus), although activation of glutamate receptors in other brain areas seems to be antinociceptive (e.g. periaqueductal grey, ventrolateral medulla).
Application of glutamate, or agonists selective for one of the several types of glutamate receptor, to the spinal cord or periphery induces nociceptive behaviours. Inhibition of glutamate release, or of glutamate receptors, in the spinal cord or periphery attenuates both acute and chronic pain in animal models. Similar benefits have been seen in studies involving humans (both patients and volunteers); however, results have been inconsistent. More research is needed to clearly define the role of existing treatment options and explore the possibilities for future drug development.
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Metadata
Title
Glutamate Receptors and Nociception
Implications for the Drug Treatment of Pain
Author
Dr Marian E. Fundytus
Publication date
01-01-2001
Publisher
Springer International Publishing
Published in
CNS Drugs / Issue 1/2001
Print ISSN: 1172-7047
Electronic ISSN: 1179-1934
DOI
https://doi.org/10.2165/00023210-200115010-00004

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