Researchers at the University of Arizona Health Sciences say they may have identified a way to make opioids safer and more effective by inhibiting a key protein in the spinal cord.
In a report published in the May 5 issue of Science Signaling, published by the American Association for the Advancement of Science, researchers said that targeting the heat shock protein 90, or Hsp90, can enhance opioids effectiveness and decrease the side effects of opioid therapy.
John Streicher, assistant professor with the University of Arizona College of Medicine in the Department of Pharmacology in Tucson, and David Duron, a graduate doctoral student found Hsp90 plays a crucial role in signaling pathways in the spinal cord that impacts how the nervous system reacts to pain.
“There are pathways that produce pain relief in the spinal cord,” said Streicher, the paper’s senior author. “It seems like heat shock protein 90 is inhibiting one of those pathways in the spinal cord and preventing it from being activated. When we give this inhibitor in the spinal cord, it unblocks that pathway, which provides another route to greater pain relief.”
The research suggests that Hsp90 inhibitors could provide doctors with a way to reduce the dosage in patient opioid medication while giving the same level of pain relief with reduced side effects.
As opioids enter the body, researchers said, they bind to a protein target with then launches a series of effects known as a “signaling cascade.” As the signaling molecules work their way through the system, they affect the body by providing different effects, such a pain relief, respiratory depression, reward, and tolerance.
“Our overall research program is looking at the signaling links between receptor activation and pain relief downstream, and one of the proteins in the middle that we’ve been studying for a number of years is called heat shock protein 90,” Streicher said. “Heat shock protein 90 does a lot of things, but one thing it does is regulate how that receptor talks to the downstream changes in your brain, like pain relief.”
Duron, who hopes to begin law school in the fall and pursue a career in intellectual property and drug discovery law, said they found that when Hsp90 was inhibited, it amplified the pain-relieving effects of morphine.
“When we found these effects in the spinal cord, my ‘aha moment’ was realizing that this could potentially be something that could have an application in the clinic,” Duron said.
Streicher said developing a clinical Hsp90 inhibitor drug is promising, but that getting any actual drug with U. S. Food and Drug Administration approval on the market would take years.
“The opioid crisis stems from a lot of factors, but one of the primary factors is that we have a real chronic pain problem in the U.S.,” Streicher said. “There are over 100 million people with some sort of chronic pain. For especially those people with moderate to severe pain, opioids are often the only efficacious options they have. So, we have a lot of people in pain, a lot of those people are still going to need to take opioids. Finding new ways to treat people’s pain without them getting addicted to some sort of pain-relieving drug is by far one of the most effective ways we have to fight the opioid crisis.”