This is a randomized Phase II study testing the effectiveness of the combination of morphine and methadone versus morphine alone in relieving pain. A second goal is to further evaluate any side effects of the combination of morphine and methadone.

Rationale: Experimental data demonstrates a profound analgesic synergy between morphine and methadone when co-administered systemically in mice. If this type of synergy can be demonstrated in clinical pain, it will be a relatively unique example of translating concepts of fundamental aspects of opioid actions seen in the laboratory to the clinical area, and provide a basis for offering new and scientifically- based analgesic regimens. This may provide better pain relief with less opioid related side effects in clinical practice.

Purpose:

This is a randomized, double blind, parallel arm Phase II study comparing a single dose of 1:1 combination of methadone and morphine with morphine alone in patients with post-operative pain.

• The primary objective of this randomized, double blind, parallel arm Phase II study is to compare the analgesic effects of a combination of morphine and methadone with morphine alone to determine synergistic activity of mu opioid analgesics in patients with post-operative pain.
• A second goal is to further evaluate any side effects of the combination of morphine and methadone.

Inclusion Criteria:

• Retroperitoneal lymph node dissection
• Planned post-operative analgesia with PCA at 1 mg continuous infusion and 1 mg every 10 minutes
• 18 years of age or older
• English-speaking
• Give informed consent to participate in this study

Exclusion Criteria:

• Known hypersensitivity to methadone or morphine
• Patients with past or present history of substance abuse
• Patients with a history of methadone treatment
• Patients with a history of chronic pain requiring daily analgesic use for more than 3 months
• Patients treated with opioids within one month from the scheduled surgery
• Creatinine clearance less than 50 mg/kg (using Cockcroft-Gault Equation).
• Neurologic or psychiatric disease sufficient, in the doctor's opinion, to compromise data collection

1 year