The long-term goal of this project is to improve the relief of pain related to cancer and its treatment. It is an extension of the investigator's previous work with BMT patients which has shown that patient-controlled analgesia (PCA) with morphine provides pain relief equal to that of continuous infusion morphine and that pain relief in BMT patients with oropharyngeal pain is always incomplete regardless of the method of morphine administration. In this project the investigators will: a) examine the relationship between plasma opioid concentration and relief of pain in patients with active mucositis and b) compare the clinical efficacy and side-effects of three drugs when used for PCA. Experiment 1 addresses the hypothesis that mu selective opioid agonists produce incomplete relief of mucositis pain at tolerable concentrations, and it will determine the shape of the concentration/response curve. It will indicate whether the partial pain relief observed clinically arises from undergoing or efficacy limitations. Experiment 2 examines the null hypothesis that there is no difference in efficacy and side-effects between morphine, hydromorphone, and sufentanil when self-administered by patients with active mucositis. These questions arise from the results of our clinical and laboratory research in the past years. In Experiment 1, the investigators will use pharmacokinetic infusion techniques developed in their laboratory. Patients with active mucositis will receive a tailored drug infusion to produce a linear increase in plasma opioid concentration over 3 hours. Every 20 minutes pain and side-effects will be assessed and blood will be drawn for opioid assay. Each patient will receive two infusions, one week apart. We will complete study of one drug each year (morphine, hydromorphone, sufentanil; N-20 each). In Experiment 2, patients will use PCA to deliver opioid analgesics in a double-blind comparison of the clinical effectiveness and side-effects of the same three analgesic drugs (N-20 per drug). This study parallels Experiment 1, in separate patients. Experiment 1 will require three years to complete; Experiment 2, all four years. In addition to the primary analyses, the investigators will undertake secondary analyses of the data from Experiment 2 in order to characterize and model individual differences on the basis of oral mucositis, pain, analgesic drug use and time. This work will apply time trace methods and empirical Bayes modeling as described in Core B.
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