Genetic enhancement of inflammatory pain by forebrain NR2B overexpression

N-methyl-D-aspartate (NMDA) receptors contribute to many brain functions. W e studied the effect of forebrain-targeted overexpression of the NMDA recep tor subunit NR2B on the response of mice to tissue injury and inflammation. Transgenic mice exhibited prominent NR2B expression and enhanced NMDA rece ptor-mediated synaptic responses in two pain-related forebrain areas, the a nterior cingulate cortex and insular cortex, but not in the spinal cord. Al though transgenic and wild type mice were indistinguishable in tests of acu te pain, transgenic mice exhibited enhanced responsiveness to peripheral in jection of two inflammatory stimuli, formalin and complete Freund's adjuvan t. Genetic modification of forebrain NMDA receptors can therefore influence pain perception, which suggests that forebrain-selective NMDA receptor ant agonists, including NR2B-selective agents, may be useful analgesics for per sistent pain.