Demonstrate that low dose morphine administered in conjunction with pramipexole is non-inferior to a standard dose of morphine in providing analgesia for acute pain.

Managing the complex risk-benefit profile of opioid therapeutics is a significant challenge. Current guidelines call for minimizing opioid doses in cases where opioids are required. Preclinical studies demonstrate that the analgesic properties of morphine are enhanced when administered in combination with the dopamine 3 receptor agonist, pramipexole (PPX), even if the dose of morphine is non-therapeutic on its own. The current study translates those findings to the clinic.

This study was reviewed and approved by the University and Medical Center Institutional Review Boards. A double-blinded, randomized non-inferiority study was performed. Participants received either intravenous morphine at 0.1mg/kg + a placebo pill, or morphine at 0.05mg/kg + a 0.25mg PPX pill. Pain scores were measured prior to and at 15-minute intervals after treatment for 120 minutes using visual analog (VAS) and numeric rating scales (NRS). Primary outcomes included clinically significant reduction in pain score (defined as ≥50% decrease) and the need for rescue medication within 30 minutes of drug administration. Trends in pain ratings across time were assessed using locally weighted smoothing (LOESS) scatter plot-smoothing curves. The difference in the proportion of patients achieving at least 50% improvement in pain at 120 minutes was analyzed with a non-inferiority margin of -.20 between groups.

Adjuvant treatment with PPX may provide a means to minimize patient exposure to opioids, reducing the associated risks.