The spinothalamic and spinoreticular tracts play important roles in renal pain and renal nociceptive reflexes. This research is designed to continue our studies of the effects of renal stimuli on these neurons. We will test the hypothesis that renal ischemia potentiates responses of spinothalamic and spinoreticular neurons to renal mechanical stimuli. A second hypothesis to be tested is that the release of renal prostaglandins is part of the mechanism by which renal ischemia influences spinal pain pathways. These experiments will be carried out on cats and monkeys that are anesthetized with alpha-chloralose. We will locate thoracolumbar spinothalamic and spinoreticular neurons that respond to electrical stimulation of renal nerves and to somatic stimuli. We will then determine the relation between increases in uretero-pelvic or renal pelvic pressure and cell activity. These relations will then be redetermined while the kidney has been made ischemic by occluding the renal artery. The effect of renal ischemia on cell responses to somatic stimuli will also be assessed. In a second series of experiments on spinothalamic cells of monkeys we will determine if the effect of ischemia on the mechanical stimulus - cell response relation is blocked by a prostaglandin synthesis blocking drug, meclofenamate. In a third series of experiments we will record the effect of prostaglandins, primarily prostaglandin E2 and prostacyclin, on cell activity and on cell responses to renal mechanical stimuli. Finally, we will determine if angiotensin II receptor blockade or kallikrein renal mechanical stimuli. These experiments will begin to describe the role of intrarenal events such as ischemia and release of prostaglandins that can modify responses of pain pathways to renal mechanical stimuli. Such information will provide new insights into the mechanisms of renal pain and renal reflexes and perhaps begin to explain the variability of renal pain.