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Neuropathic pain model of peripheral neuropathies mediated by mutations of glycyl-tRNA synthetase.

Abstract
Charcot-Marie-Tooth disease (CMT) is the most common inherited motor and sensory neuropathy. Previous studies have found that, according to CMT patients, neuropathic pain is an occasional symptom of CMT. However, neuropathic pain is not considered to be a significant symptom associated with CMT and, as a result, no studies have investigated the pathophysiology underlying neuropathic pain in this disorder. Thus, the first animal model of neuropathic pain was developed by our laboratory using an adenovirus vector system to study neuropathic pain in CMT. To this end, glycyl-tRNA synthetase (GARS) fusion proteins with a FLAG-tag (wild type [WT], L129P and G240R mutants) were expressed in spinal cord and dorsal root ganglion (DRG) neurons using adenovirus vectors. It is known that GARS mutants induce GARS axonopathies, including CMT type 2D (CMT2D) and distal spinal muscular atrophy type V (dSMA-V). Additionally, the morphological phenotypes of neuropathic pain in this animal model of GARS-induced pain were assessed using several possible markers of pain (Iba1, pERK1/2) or a marker of injured neurons (ATF3). These results suggest that this animal model of CMT using an adenovirus may provide information regarding CMT as well as a useful strategy for the treatment of neuropathic pain.
AuthorsSeo Jin Lee, Ah Jung Seo, Byung Sun Park, Hyun Woo Jo, Youngbuhm Huh
JournalJournal of Korean medical science (J Korean Med Sci) Vol. 29 Issue 8 Pg. 1138-44 (Aug 2014) ISSN: 1598-6357 [Electronic] Korea (South)
PMID25120326 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Glycine-tRNA Ligase
Topics
  • Animals
  • Charcot-Marie-Tooth Disease (diagnosis, physiopathology)
  • Disease Models, Animal
  • Glycine-tRNA Ligase (genetics, metabolism)
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Mutagenesis, Site-Directed
  • Mutation (genetics)
  • Neuralgia (diagnosis, physiopathology)

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