Chronic pain is crippling America, impacting one in five adults and costing an astonishing $600 billion annually in medical expenses and lost productivity. As the U.S. grapples with this widespread issue, researchers are stepping up to devise innovative, non-opioid solutions for pain management.

Stanton McHardy, the visionary director of the Center for Innovative Drug Discovery (CIDD), is leading three pioneering research initiatives focused on creating safe pain relief options that don’t rely on the notorious opioids, known for their risk of addiction and overdose.

The Opioid Crisis: A Troubling Trend

In Texas, opioids have become the go-to prescription for pain, but the consequences are dire. Over the last five years, drug poisoning deaths—largely from opioid overdoses—have skyrocketed by over 75%, according to the state’s Department of State Health Services.

"These research projects are about finding better solutions," states McHardy. "Developing novel non-opioid medications is of paramount medical significance and holds tremendous societal benefits."

Targeting Pain at Its Source

Teaming up with Kenneth M. Hargreaves from UT Health San Antonio, McHardy is focusing on small-molecule inhibitors that target the pain-related enzyme PLA2. Their goal? To create effective, non-addictive medications that could prevent opioid use disorder before it even begins.

McHardy emphasizes, "My work at UTSA centers around designing and optimizing small molecules through medicinal chemistry. This expertise will help us discover powerful inhibitors for non-opioid pain relief therapeutics."

Innovative Strategies for Pain Management

In another exciting project, McHardy collaborates with pharmacology experts William Clarke and Kelly Berg to develop an unconventional pain management method—targeting pain-sensing nerves rather than the brain.

Their approach zeroes in on two specific receptors, the delta opioid receptor (DOR) and kappa opioid receptor (KOR), which form a unique DOR-KOR heteromer that, when activated, significantly alleviates pain without the opioid-related risks.

Advancements in Medicinal Chemistry

Kallee Diaz, a PhD student at UTSA, is diving deep into medicinal chemistry research, while Daniel Rounds, a senior chemistry major, receives mentorship from expert Nick Clanton in molecular modeling. Together, they aim to uncover compounds that work specifically on the DOR-KOR heteromer, potentially leading to a revolutionary class of painkillers.

Beyond Conventional Treatments

Current treatment options remain limited and often involve prolonged use of opioids, which can lead to reduction in effectiveness over time. In a groundbreaking study recently published in JCI Insight, McHardy and his collaborators addressed chemotherapy-induced peripheral neuropathy (CIPN), a severe condition afflicting nearly half of chemotherapy patients.

Their innovative compound, CP612, which blocks the enzyme PKCε, proved effective in reducing chemotherapy-related nerve pain and easing opioid withdrawal symptoms—without addiction or interference with other medications.

As McHardy’s lab continues to push the boundaries of pain relief research, the promise of non-opioid alternatives shines brighter than ever, potentially transforming the landscape of pain management for millions.