Peripheral Demyelination and Neuropathic Pain Behavior in Periaxin-Deficient Mice

The Prx gene in Schwann cells encodes L- and S-periaxin, two abundant PDZ domain proteins thought to have a role in the stabilization of myelin in the peripheral nervous system (PNS). Mice lacking a functional Prx gene assemble compact PNS myelin. However, the sheath is unstable, leading to demyelin...

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Bibliographic Details
Published in:Neuron (Cambridge, Mass.) Mass.), 2000-05, Vol.26 (2), p.523-531
Main Authors: Gillespie, C.Stewart, Sherman, Diane L., Fleetwood-Walker, Susan M., Cottrell, David F., Tait, Steven, Garry, Emer M., Wallace, Victoria C.J., Ure, Jan, Griffiths, Ian R., Smith, Austin, Brophy, Peter J.
Format: Article
Language:English
Subjects:
Animals
Axons - ultrastructure
Behavior, Animal
Demyelinating Diseases - complications
Demyelinating Diseases - genetics
Demyelinating Diseases - pathology
Electrophysiology
Excitatory Amino Acid Antagonists - pharmacology
Humans
Hyperalgesia - genetics
Hyperalgesia - physiopathology
Membrane Proteins - deficiency
Membrane Proteins - genetics
Mental Disorders - etiology
Mice
Mice, Knockout - genetics
Neural Conduction
Pain - etiology
Pain - psychology
periaxin
Peripheral Nerves - physiopathology
Peripheral Nervous System Diseases - complications
Peripheral Nervous System Diseases - genetics
Peripheral Nervous System Diseases - pathology
Prx gene
Schwann Cells - ultrastructure
Somatosensory Disorders - genetics
Somatosensory Disorders - physiopathology
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Summary:The Prx gene in Schwann cells encodes L- and S-periaxin, two abundant PDZ domain proteins thought to have a role in the stabilization of myelin in the peripheral nervous system (PNS). Mice lacking a functional Prx gene assemble compact PNS myelin. However, the sheath is unstable, leading to demyelination and reflex behaviors that are associated with the painful conditions caused by peripheral nerve damage. Older Prx −/− animals display extensive peripheral demyelination and a severe clinical phenotype with mechanical allodynia and thermal hyperalgesia, which can be reversed by intrathecal administration of a selective NMDA receptor antagonist. We conclude that the periaxins play an essential role in stabilizing the Schwann cell–axon unit and that the periaxin-deficient mouse will be an important model for studying neuropathic pain in late onset demyelinating disease.
ISSN:0896-6273
1097-4199
DOI:10.1016/S0896-6273(00)81184-8