title: The glutamatergic system as a target for neuropathic pain relief.
abstract: Glutamate is the major excitatory neurotransmitter in the mammalian CNS. The understanding of glutamatergic transmission in the nervous system has been greatly expanded with the discovery and investigation of the family of ionotropic and metabotropic glutamate receptors (mGluRs). Metabotropic glutamate receptors are localized at nerve terminals, postsynaptic sites and glial cells and thus, they can influence and modulate the action of glutamate at different levels in the synapse. Moreover, there is substantial evidence of glial participation in glutamate nociceptive processes and neuropathic pain. Metabotropic glutamate receptors have been shown to play a role in neuropathic pain, which is one of the most troublesome illnesses because the therapy is still not satisfactory. Recently, the development of selective mGluR ligands has provided important tools for further investigation of the role of mGluRs in the modulation of chronic pain processing. This paper presents a review of the literature of glutamate receptors in neuropathic pain and the role of glia in these effects. Specifically, pharmacological interventions aimed at inhibiting group I mGluRs and/or potentiating group II and III mGluR-mediated signalling is discussed. Moreover, we introduce data about the role of glutamate transporters. They are responsible for the level of glutamate in the synaptic cleft and thus regulate the effects of all three groups of mGluRs and, in consequence, the activity of this system in nociceptive transmission. Additionally, the question of how the modulation of the glutamatergic system influences the effectiveness of analgesic drugs used in neuropathic pain therapy is addressed.
authors.affiliation: Department of Pain Pharmacology, Institute of Pharmacology, Polish Academy of Sciences, Krakow, Poland.
authors.forename: Maria
authors.initials: M
authors.lastname: Osikowicz
authors.forename: Joanna
authors.initials: J
authors.lastname: Mika
authors.forename: Barbara
authors.initials: B
authors.lastname: Przewlocka
mesh_terms: D000700:Analgesics / Q000494:pharmacology*; D000818:Animals; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology*; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology*; D050491:Glutamate Plasma Membrane Transport Proteins / Q000187:drug effects / Q000378:metabolism; D018698:Glutamic Acid / Q000378:metabolism*; D006801:Humans; D008024:Ligands; D009437:Neuralgia / Q000188:drug therapy* / Q000378:metabolism; D009457:Neuroglia / Q000187:drug effects* / Q000378:metabolism; D018094:Receptors, Metabotropic Glutamate / Q000187:drug effects / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*; D050496:Vesicular Glutamate Transport Proteins / Q000187:drug effects / Q000378:metabolism
chemical_list: D000700:Analgesics; D018690:Excitatory Amino Acid Agonists; D018691:Excitatory Amino Acid Antagonists; D050491:Glutamate Plasma Membrane Transport Proteins; D008024:Ligands; D018094:Receptors, Metabotropic Glutamate; D050496:Vesicular Glutamate Transport Proteins; D018698:Glutamic Acid