Breakthrough in opioid safety research: Protein inhibitors may reduce risks

TUCSON, Ariz. – Researchers have identified a new way to potentially make opioids safer. By inhibiting a specific isoform of Heat Shock Protein 90 (Hsp90), University of Arizona Health Sciences researchers found that it’s possible to enhance the pain-relieving properties of opioids while reducing their unwanted side effects.

“This is the critical link that makes our work translationally relevant, giving us a clear path forward to develop a new drug that could benefit millions of people who live with chronic pain,” researcher John Streicher said in a University of Arizona Health Sciences press release.

Hsp90 is known for its role in supporting other proteins, including those involved in tumor growth. Although primarily studied in cancer research, Streicher has focused on how Hsp90 activates opioid receptors.

The team’s research showed that inhibiting Hsp90 in the spinal cords of mice significantly increased the potency of morphine’s pain relief—by two to four times. Additionally, this approach reduced tolerance to the drug and even reversed existing tolerance. Streicher envisions a future where patients could take a combination pill containing an opioid and an Hsp90 isoform inhibitor, allowing for lower doses with fewer side effects.

More than 107,500 Americans died from drug overdoses in 2023, with many of the deaths related to opioids. This breakthrough could offer a new path forward in addressing the opioid crisis.