Endogenous neuropeptides were studied to determine their effects on communication between neurons in the central nervous system. Studies were carried out to characterize the effects of the peptides on A) synaptic currents and B) extracellularly recorded potentials from large populations of neurons. A) In the CA3 region of the guinea pig hippocampus neurons receive a number of synaptic inputs from other areas of the brain. One of these inputs contains the endogenous neuropeptide dynorphin. Using whole cell voltage clamp in living slices of brain tissue, we have discovered that dynorphin produces an increase in the synaptic current evoked by a specific class of receptor known as the N-methyl-d-aspartate receptor. The increase in this current indicates that communication between the cells has been enhanced. Dynorphin and N-methyl-d-aspartate receptors in the spinal cord are an important part of the processes involved with chronic pain. Thus, efforts are underway to develop a living spinal cord slice preparation in order to determine the effect dynorphin has on synaptic currents in that tissue. B) Using standard extracellular recording techniques in the CA1 region of the rat hippocampal slice, we have discovered a potential that corresponds to the event related potential (p300) that is studied in humans. This in vitro potential has not been reported in the literature previously. The p300 is associated with the perception of external stimuli, including pain. Efforts are underway to further characterize this potential and to determine the effect neuropeptides have on this potential. The significance of this project is to understand the role neuropeptides play in pain processes at the molecular, cellular and network levels. With this knowledge novel treatment strategies for chronic pain can be developed.
