Genetic enhancement of inflammatory pain by forebrain NR2B overexpression.
N-methyl-D-aspartate (NMDA) receptors contribute to many brain functions. We studied the effect of forebrain-targeted overexpression of the NMDA receptor subunit NR2B on the response of mice to tissue injury and inflammation. Transgenic mice exhibited prominent NR2B expression and enhanced NMDA receptor-mediated synaptic responses in two pain-related forebrain areas, the anterior cingulate cortex and insular cortex, but not in the spinal cord. Although transgenic and wild type mice were indistinguishable in tests of acute pain, transgenic mice exhibited enhanced responsiveness to peripheral injection of two inflammatory stimuli, formalin and complete Freund's adjuvant. Genetic modification of forebrain NMDA receptors can therefore influence pain perception, which suggests that forebrain-selective NMDA receptor antagonists, including NR2B-selective agents, may be useful analgesics for persistent pain.
Wei
F
F
Washington University Pain Center and Departments of Anesthesiology, Anatomy & Neurobiology, and Psychiatry, Washington University School of Medicine, Campus Box 8054, 660 S. Euclid Ave., St. Louis, Missouri 63110, USA.
Wang
G D
GD
Kerchner
G A
GA
Kim
S J
SJ
Xu
H M
HM
Chen
Z F
ZF
Zhuo
M
M
D000818:Animals; D004660:Encephalitis / Q000503:physiopathology*; D005557:Formaldehyde / Q000494:pharmacology; D005620:Freund's Adjuvant / Q000494:pharmacology; D006614:Hindlimb; D007267:Injections; D008297:Male; D051379:Mice; D008822:Mice, Transgenic / Q000235:genetics; D010146:Pain / Q000503:physiopathology*; D017288:Pain Threshold / Q000187:drug effects / Q000502:physiology; D016548:Prosencephalon / Q000378:metabolism*; D016194:Receptors, N-Methyl-D-Aspartate / Q000235:genetics / Q000378:metabolism*; D012016:Reference Values; D013569:Synapses / Q000502:physiology
C121001:NR2B NMDA receptor; D016194:Receptors, N-Methyl-D-Aspartate; D005557:Formaldehyde; D005620:Freund's Adjuvant