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PDZ domains at excitatory synapses: potential molecular targets for persistent pain treatment.

Authors
  • Tao, Yuan-Xiang1
  • Johns, Roger A
  • 1 Department of Anesthesiology and Critical Care Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA. [email protected]
Type
Published Article
Journal
Current Neuropharmacology
Publisher
Bentham Science
Publication Date
Jul 01, 2006
Volume
4
Issue
3
Pages
217–223
Identifiers
PMID: 18615145
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

Persistent pain, a common clinical condition, could be caused by inflammation, tissue injury secondary to trauma or surgery, and nerve injuries. It is often inadequately controlled by current treatments, such as opioids and nonsteroidal anti-inflammatory drugs. The PDZ (Postsynaptic density 95, Discs large, and Zonula occludens-1) domains are ubiquitous protein interaction modules often found among multi-protein signaling complexes at neuronal synapses. Recent preclinical research shows that targeted disruption of PDZ domain-mediated protein interaction among N-methyl-Daspartate (NMDA) receptor signaling complexes significantly attenuates the development and maintenance of persistent pain without affecting nociceptive responsiveness to acute pain. PDZ domains at excitatory synapses may be new molecular targets for prevention and treatment of persistent pain. Here, we illustrate expression and distribution of the PDZ domain-containing proteins associated with NMDA receptors in the pain-related regions of the central nervous system, review the evidence for their roles in persistent pain states, and discuss potential mechanisms by which these PDZ domain-containing proteins are involved in persistent pain.

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