The role of glutamate signaling in pain processes and its regulation by GCP II inhibition

K. M. Wozniak, Camilo Rojas, Y. Wu, Barbara Slusher

Research output: Contribution to journalArticle

Abstract

Glutamate is the predominant excitatory neurotransmitter used by primary afferent synapses and neurons in the spinal cord dorsal horn. Glutamate and glutamate receptors are also located in areas of the brain, spinal cord and periphery that are involved in pain sensation and transmission. Not surprisingly, glutamate receptors have been an attractive target for new pain therapies. However, their widespread distribution and array of function has often resulted in drugs targeting these sites having undesirable side-effects. This chapter will review, in general terms, the current knowledge of glutamate and its effects at various glutamate receptors with regards to nociception. In addition, we will briefly review the glutamatergic drugs currently in use as treatments for pain, as well as known novel candidates in various stages of clinical trial. Lastly, we will summarize the data supporting a novel target for pain intervention by way of GCPII inhibition, which appears devoid of the side-effects associated with direct glutamate receptor antagonists and thus holds major promise for future therapy. GCPII (glutamate carboxypeptidase II) cleaves the prevalent neuropeptide NAAG into NAA and glutamate and there is widespread evidence and belief that targeting the glutamate derived from this enzymatic action may be a promising therapeutic route.

Original languageEnglish (US)
Pages (from-to)1323-1334
Number of pages12
JournalCurrent Medicinal Chemistry
Volume19
Issue number9
DOIs
StatePublished - Mar 2012

Fingerprint

Glutamic Acid
Glutamate Carboxypeptidase II
Glutamate Receptors
Pain
Afferent Neurons
Excitatory Amino Acid Antagonists
Nociception
Therapeutics
Drug Delivery Systems
Neuropeptides
Synapses
Neurons
Neurotransmitter Agents
Brain
Spinal Cord
Inhibition (Psychology)
Clinical Trials
Pharmaceutical Preparations

Keywords

  • Central nervous system
  • dorsal horn
  • Glutamate Carboxypeptidase II (GCPII)
  • glutamate receptors
  • NAAG
  • neuropathy
  • pain
  • peripheral nervous system

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmacology

Cite this

The role of glutamate signaling in pain processes and its regulation by GCP II inhibition. / Wozniak, K. M.; Rojas, Camilo; Wu, Y.; Slusher, Barbara.

In: Current Medicinal Chemistry, Vol. 19, No. 9, 03.2012, p. 1323-1334.

Research output: Contribution to journalArticle

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