The preventive and therapeutic effects of GCPII (NAALADase) inhibition on painful and sensory diabetic neuropathy

W. Zhang, Y. Murakawa, K. M. Wozniak, B. Slusher, A. A.F. Sima

Research output: Contribution to journalArticlepeer-review

Abstract

Excitotoxic glutamate release occurs in several neurological disorders. One source is derived from the hydrolysis of the neuropeptide N-acetyl aspartyl glutamate (NAAG) by glutamate carboxypeptidase II (GCPII, also known as NAALADase). Drugs that attenuate glutamate transmission have been shown to relieve neuropathic pain, however side effects have limited their clinical use. It appears that GCPII is exclusively recruited to provide a glutamate source in hyperglutamatergic, excitotoxic conditions and therefore would be devoid of such side effects. Here we report on the therapeutic effects of an orally bio-available GCP II inhibitor on established painful and sensory neuropathy in the spontaneously diabetic BB/Wor rat. It significantly improved hyperalgesia, nerve conduction velocity and underlying myelinated fiber atrophy. The data suggest that GCP II inhibition may provide a meaningful and effective approach to the treatment of painful diabetic neuropathy.

Original languageEnglish (US)
Pages (from-to)217-223
Number of pages7
JournalJournal of the Neurological Sciences
Volume247
Issue number2
DOIs
StatePublished - Sep 25 2006
Externally publishedYes

Keywords

  • BB/Wor rat
  • GCPII inhibition
  • Nociception
  • Sensory diabetic neuropathy

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology

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