Prami Grant uri icon

abstract

  • Opioid analgesics are the most commonly prescribed class of medications and are highly effective in controlling acute pain. However, in chronic pain conditions, opioids lose their effect over time and carry a high risk of addiction and physical dependence on the drug. There is a critical need to develop drug combinations that take advantage of the opioid's pain-relieving effect while preventing addiction. In animal models, a drug combination of morphine (opioid drug) and pramipexole (a dopamine 3 receptor agonist used to treat Parkinson's disease and Restless Legs syndrome) provides superior analgesia against acute painful stimuli than morphine alone, suggesting that this drug combination may also be provide superior pain relief in humans. Even more importantly, we found that chronic co-administration of the two compounds prevented the development of opioid tolerance. This finding is in line with a clinical case report (manuscript submission in progress) that also describes the beneficial effect of an opioid / dopamine-agonist combination to restore pain control in a patient with restless legs syndrome, for whom opioids alone had lost their effectiveness. As a first translational study for acute pain, we propose to assess the analgesic effects of morphine alone compared to morphine in combination with pramipexole in patients suffering from renal colic. Pramipexole is an FDA-approved drug that has not previously been used to treat pain, although it works through the same intracellular mechanisms as morphine. This overlapping mechanism of action should allow morphine and pramipexole to act synergistically to improve analgesia. We expect that this drug combination will produce analgesia at a low dose of morphine that is not effective when tested on its own. As a positive side effect, a reduction of the opioid dose need to achieve analgesia will also reduce the rewarding effect of morphine and decrease the risk of developing tolerance to the drug. The technical goal of this project is to test the efficacy of this new therapeutic approach for treatment of a common painful condition using a novel combination of 2 existing, FDA-approved drugs. The immediate goal is to demonstrate that this drug combination can provide analgesia similar to a standard opioid dose, when that dose is reduced by 50%.

date/time interval

  • August 2019 - January 2023