Glutamate receptors and persistent pain: targeting forebrain NR2B subunits

• Published in: Drug Discovery Today Vol. 7; no. 4; pp. 259 - 267
• Main Author: Zhuo, Min
• Format: Book Review Journal Article
• Language: English
• Published: Oxford Elsevier Ltd 15-02-2002; Elsevier Science
• Subjects: Aminoacid receptors (glycine, glutamate, gaba); Analgesics; Animals; Biological and medical sciences; Cell receptors; Cell structures and functions; Chronic Disease; Combinatorial Chemistry Techniques; Feedback - physiology; Fundamental and applied biological sciences. Psychology; Humans; Medical sciences; Molecular and cellular biology; neurokinin A; Neuropharmacology; pain; Pain - drug therapy; Pain - physiopathology; Pharmacology. Drug treatments; Prosencephalon - physiology; rat; Receptors, Glutamate - drug effects; Receptors, Glutamate - physiology; Receptors, N-Methyl-D-Aspartate - drug effects; Receptors, N-Methyl-D-Aspartate - physiology; Somesthesis and somesthetic pathways (proprioception, exteroception, nociception); interoception; electrolocation. Sensory receptors; spinal cord; Spinal Cord - physiopathology; substance P; Synaptic Transmission; Vertebrates: nervous system and sense organs; pain; Toxicology; rat; Techniques & Methods; Pharmaceutical Science; Neurobiology; neurokinin A; Pharmacology; Molecular Medicine; spinal cord; substance P; Drug Discovery; Human; Nociception; Spinal cord; Substance P; Central nervous system; Glutamate receptor; Review; Gene expression; In vitro; In vivo; Analgesic; Pain; Synaptic transmission; Animal; Synaptic plasticity; Mechanism of action; NMDA receptor; Brain (vertebrata)
• ISSN: 1359-6446; 1878-5832
• DOI: 10.1016/S1359-6446(01)02138-9

Glutamate is the fast excitatory transmitter in mammalian brains. It binds to two major classes of glutamate receptors: ionotropic and metabotropic receptors. Ionotropic receptors contain three subtype receptors, including N-methyl-d-aspartate (NMDA) receptors. Activation of NMDA receptors is important for initiating long-lasting changes in synapses. In the forebrain structures that are known to contribute to the formation and storage of information, NMDA receptors have an important role in persistent inflammatory pain by reinforcing glutamate sensory transmission. Mice with enhanced forebrain NMDA receptor function demonstrate selective enhancement of persistent pain and allodynia. Drugs targeting NMDA NR2B subunits in the forebrain could serve as a new class of medicine for controlling persistent pain in humans.