Grant: Operating Grant

Neurotransmitter receptors are normally found on the outer cell membrane of nerve cells or neurons. Some receptors have been found as well inside neurons on the membrane of the cell's nucleus. We propose to examine whether increases in newly discovered nuclear membrane receptors for the neurotransmitter glutamate in spinal cord, along with the ones on the cell membrane, contribute to enhanced pain responses in rats with persistent pain. We will assess whether these receptors are increased in rats with hind paw inflammation or nerve injury, and whether there is increased binding and activity of glutamate at cell membrane and nuclear receptors in these rats. Finally, we wish to determine whether drugs which prevent transport of glutamate into cells reduce enhanced pain after inflammation or nerve injury because they prevent glutamate from getting to neuronal nuclear receptors. We will test this hypothesis against previously proposed theories that these drugs block abnormal pumping of glutamate back into the synapse (from the glial cells which normally take glutamate out of synapses), or cause excess glutamate binding at inhibitory receptors on the nerve cells that release glutamate, therefore stopping further glutamate release.