Comparison of A Single Dose Combination of Methadone and Morphine With Morphine Alone for Treating Post-operative Pain

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