Researchers have discovered a novel way to handle moderate to severe pain that paves the way for lower dosage painkillers.
When people try to manage chronic pain, many turn to painkilling drugs such as morphine and Vicodin. Unfortunately, the body has a natural tendency to develop a tolerance to these medications, and this often means that the patient will begin taking higher doses—increasing risks of harmful side effects and dependency.
Commonly prescribed painkillers, such as hydrocodone (the main ingredient in Vicodin) and oxycodone (Oxycontin), bind to specific molecules (opioid receptors) on nerve cells in the brain and spinal cord to prevent the feeling of pain.
“We have for the first time discovered compounds that bind to an alternative site on the nerve opioid receptors and that have significant potential to enhance the drug’s positive impact without increasing negative side effects,” said co-author John Traynor, Ph.D., professor of pharmacology at the University of Michigan Medical School.
“We are still in the very early stages of this research with a long way to go, but we believe identifying these compounds is a key step in revolutionizing the treatment of pain.
“This opens the door to developing pain relief medications that require lower doses to be effective, helping address the serious issues of tolerance and dependence that we see with conventional pain therapy.”
Conventional drug treatments for pain target the so-called orthosteric site of the opioid receptor that provides pain relief. This is a double-edged sword, however, because this site is also responsible for all of the drug’s negative side effects, including constipation and respiratory depression. Tolerance also limits chronic use of the drugs because higher doses are required to maintain the same effect.
Scientists have now identified compounds that bind to a newly discovered site on the opioid receptor — a site that fine-tunes the activity of the receptor. Not only do these compounds act at a location that hasn’t been studied as a drug target before, but they bind to the receptor in a new way to intensify the actions of morphine.
This means that lower doses can have the same effect.
“The newly-discovered compounds bind to the same receptor as morphine but appear to act at a separate novel site on the receptor and therefore can produce different effects. What’s particularly exciting is that these compounds could potentially work with the body’s own natural painkillers to manage pain,” said Traynor.
The findings appear in Proceedings of the National Academy of Sciences.