The long-term objective of this research program is to identify the mechanism by which vaginocervical stimulation (VS) in rats reflexively blocks pain, and thereby to develop a rational basis for augmenting its effect via the relevant neurotransmitters, ultimately for the control of pain in humans. The specific aims of the present proposal utilizing rats are 1) to test our current concept of the specific neural circuitry underlying the VS- produced pain blockage (based on previous neurophysiological, neuropharmacological, and lesion studies) by using the 2- deoxyglucose autoradiographic method and 2) to determine the extent to which vs, which occurs naturally during parturition, elevates pain thresholds in relation to phasic increases in intracervical pressure, as the fetuses pass through the birth canal, and to augment this analgesia pharmacologically. The 2-DG autoradiographic study is Byron Johnson's doctoral dissertation. Autoradiographs will be analyzed quantitatively by computerized image analysis. Four stimulus groups will be utilized: a) VS-only; b) noxious stimulation (hind foot pressure) only; c) concurrent VS and hind foot pressure; d) control (neither VS nor hind foot pressure). We will focus initially on relative activity in the ventrobasal complex of the thalamus, ventral horn flexor region, spinothalamic cell body regions of the lumbar spinal cord, and noradrenergic and serotoninergic cell body groups in the lower brain stem. We expect that VS will block noxious stimulation-induced activation in the first three regions without by itself activating them, whereas VS will produce activation in the latter two regions. Pain thresholds as a function of natural VS occurring in parturition. In rats, a subminiature pressure transducer will be surgically implanted in the cervix in order to measure pressure as each fetus passes through the birth canal. Using the test of tail withdrawal latency from 55 degree C water, pain thresholds will be measured before, during, and after delivery of each fetus. Based on pilot data we expect that pain thresholds will increase in direct relation to variations in pressure in the birth canal during the birth of each fetus. A protease inhibitor leupeptin, will be administered directly to the spinal cord, a procedure that we expect, based on pilot studies, will prolong the increase in pain threshold associated with delivery of individual rat pups.