This project will examine the relationships between plasma opioid concentration, analgesia and opioid side-effects for various opioid analgesics in the human studies laboratory. The investigators will evaluate concentration-effect relationships of full mu receptor agonists (sufentanil and hydromorphone), agonist/antagonists (nalbuphine and butorphanol), a partial agonist (buprenorphine), and morphine-6-glucuronide which is an active metabolite of morphine. Their experimental pain model uses dental stimulation to produce reliable, graded pain in experimental subjects. The investigators will use individual pharmacokinetic tailoring methods to control and experimentally vary plasma drug concentrations. During baseline and at three targeted plasma opioid concentrations in each test period, the investigators will measure 1) pain intensity reports and evoked potential amplitude, 2) respiratory function, 3) cognition and motor function, 4) pupil diameter, and 5) subject reports of nausea, sedation, and mood. The investigators will use the data from these experiments to calculate equally effective plasma concentrations for the six opioids in the study and to determine the intensity of side-effects produced by each drug at its half-maximal analgesic plasma concentration. This project will allow us to determine whether the analgesia-to-side-effect ratios differ between opioids (e.g., sufentanil vs. hydromorphone, nalbuphine vs. butorphanol). Results of this study will indicate whether cancer pain patients could benefit from more appropriate selection of opioid analgesics for long-term pain management.
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