The research activities of Dr. Inturrisi's laboratory are directed toward the development of methods for the alleviation of pain and drug addiction. To test the hypothesis that glutamatergic receptors in the spinal cord dorsal horn (SCDH) mediate the neuronal plasticity that is manifest as pain following injury, his lab has developed a conditional (spatial-temporal) knockout of the NMDA receptor that is confined to the lumbar spinal cord. This knockout exhibits normal motor, tactile and acute protective pain thresholds but lacks NMDA currents in the SCDH and is not affected by injury-induced pain. This model is being extended to other glutamatergic receptors (AMPA) and other effects (spinal opioid tolerance). The role of glutamatergic receptors in the addictive behaviors resulting from the administration of cocaine and opioids and mediated by the mesolimbic dopamine system are being investigated by preparing spatial-temporal knockouts of NMDA and AMPA receptors in the nucleus accumbens and ventral tegmental reward areas of the brain. Molecular, biochemical and histochemical techniques are used to identify the changes in gene and protein expression that are associated with these molecular genetic and behavioral alterations. At the clinical level, his group discovered that the d isomer of methadone is a nonopioid, NMDA receptor antagonist in animal studies and they now plan to evaluate the safety and efficacy of this compound in patients with pain.

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Dr. Inturrisi's Lab Website: Inturrisi Lab