Opioids have been used for thousands of years as analgesics. Morphine is still one
of the most effective drugs for treating severe pain. Unfortunately, prolonged use of opioids leads to tolerance where increased doses are required to maintain the same level of pain relief. There are currently no alternative analgesics to replace opioids and so an innovative approach is required to develop new drugs or adjunct therapies to mitigate the multiple negative side effects and transform the treatment of severe pain.
Researchers at the University of Dundee have established a method of altering the consequences of opioid receptor activation, potentially eliminating the adverse side effects associated with opioid use. They have shown that mice genetically engineered to lack a protein that regulates receptors in the pain pathway have a negligible tolerance to opioid analgesia. In turn, the researchers have identified a target protein that is recruited to the receptor by the regulatory protein; by inhibiting this target with a drug currently approved for use in patients for a different purpose, the researchers show that opioid analgesic tolerance is eliminated. Ongoing research will determine whether inhibitors of the target protein suppress opioid induced respiratory depression and constipation. The researchers have shown for the first time that inhibition of the target after prolonged morphine treatment can actually reverse established analgesic tolerance. With negligible tolerance and reduced effects of respiratory depression, a regular dose of opioid couldbe administered, substantially decreasing the potential for misuse and overdose. Thesuccessful application of this drug alongside standard opioids as an adjunct therapy mayenable pain relief without debilitating side effects, transforming the management ofsevere and chronic pain.