Opioid analgesics are among the most commonly prescribed class of medications in the US.
While opioids may effectively control pain and other sensory disorders under acute
conditions, the rates of misuse/abuse and accidental overdose have reached epidemic
proportions. Clinicians are being challenged to find alternatives to opioid analgesics, or to
reduce their use in treating pain whenever possible. Pre-clinical studies have shown that
combining morphine (opioid drug) with pramipexole (dopamine 3 receptor agonist with some
D2/D4 action) provides superior analgesia against painful stimuli than morphine alone. This
analgesia is maintained even when the dose of morphine is lowered to a dose that is not
effective on its own. A recent case report describes the use of this combination to restore
pain control in a patient with restless legs syndrome, for which opioids alone have lost
their effectiveness (Happe S, Clemens S and Brewer KL, In Review). This application proposes
to establish a new therapeutic approach for treatment of a pain associated with renal colic
(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 similar analgesia to
opioid alone, and that analgesia is maintained when the opioid dose is reduced by 50%.