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 domaincontaining proteins are involved in persistent pain.
Keywords: PSD-93, PSD-95, NMDA receptors, AMPA receptors, Trafficking, Spinal cord, Persistent pain, Chronic pain
Current Neuropharmacology
Title: PDZ Domains at Excitatory Synapses: Potential Molecular Targets for Persistent Pain Treatment
Volume: 4 Issue: 3
Author(s): Yuan-Xiang Tao and Roger A. Johns
Affiliation:
Keywords: PSD-93, PSD-95, NMDA receptors, AMPA receptors, Trafficking, Spinal cord, Persistent pain, Chronic pain
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 domaincontaining proteins are involved in persistent pain.
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Cite this article as:
Tao Yuan-Xiang and Johns A. Roger, PDZ Domains at Excitatory Synapses: Potential Molecular Targets for Persistent Pain Treatment, Current Neuropharmacology 2006; 4 (3) . https://dx.doi.org/10.2174/157015906778019473
DOI https://dx.doi.org/10.2174/157015906778019473 |
Print ISSN 1570-159X |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-6190 |
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