This human studies laboratory project will improve the investigators' understanding of epidural opioid analgesia and help establish conditions that will achieve optimal epidural analgesia. Effective dosage regimens, mechanism of action, and the side-effects of epidural morphine are well known. Highly lipid-soluble opioids may cause fewer side-effects than morphine, but there are many unresolved issues involving their use as selective spinal analgesics. The investigators will: 1) Compare the relative potencies, spread of effects, and incidence and severity of side- effects of epidural fentanyl, sufentanil, and alfentanil; 2) Evaluate the relative contributions of spinal and systemic effects to analgesia by comparing epidural and intravenous opioid infusions; and 3) Determine whether proglumide, a cholecystokinin antagonist, enhances epidural opioid analgesia. This effort will complement other ongoing projects in the Pain and Toxicity Research Program. This effort requires support from the Pharmacology Core for plasma drug concentration analysis, and the Administration and Services Core for algesimetric and respiratory drive testing and statistical analysis.
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