UT researchers discover new pain treatment

Areeba Khwaja

Opioids are prescribed by doctors for chronic pain management; however, according to the Department of Health and Human Services, 78 people die per day from an opioid-related overdose. 

UT chemistry researchers Stephen Martin and James Sahn published a paper in ACS Chemical Neuroscience earlier this month about a new pain reliever, a compound called UKH-1114, synthesized in their lab. Sahn published a paper in ACS Chemical Neuroscience earlier this month about a new pain reliever, a compound called UKH-1114, which they synthesized in their lab. The compound acts on the sigma-2 receptor, a receptor found in the brain and spinal cord.

In collaboration with a University of Texas at Dallas research team, Martin and Sahn also were the first to discover that the sigma-2 receptor is involved in a pathway that alleviates pain. Previously, scientists knew about the sigma-2 receptor but had not confirmed its involvement with pain.

“We have discovered that compounds that interact with the sigma-2 receptor can dramatically relieve neuropathic pain in a mouse model,” Martin said.  

Current treatments for pain management, including opioids and gabapentin, a drug mimicking the neurotransmitter GABA, come with numerous side effects.

“Opioids are addictive with a number of other adverse side effects, while gabapentin is often ineffective and can cause cognitive impairment,” Martin said, “This [discovery] opens the door to the possibility of developing a non-opioid pain reliever.”

Although further study is required, UKH-1114 could possibly be used to alleviate neuropathic pain originating from diabetes, injuries and chemotherapy, among a variety of other conditions.

“Preliminary studies show that UKH-1114 is as effective as gabapentin in a mouse model of neuropathic pain, but at a lower dose and with longer duration of action,” Sahn said. 

According to their paper, current pain medications are often ineffective: Antidepressants such as monoamine oxidase inhibitors achieve 50 percent pain relief in only one out of four patients, while gabapentinoids, or drugs derived from GABA, are only effective in one out of seven patients. In contrast, UKH-1114 is as effective as gabapentin at one-tenth the dose and lasts longer than gabapentin, Sahn said.

Since UKH-1114 appears to work through a non-opioid pathway, Sahn said it is possible that its binding to the sigma-2 receptor can reduce pain without causing the same issues involved in opioid treatment. The researchers have also discovered that, unlike gabapentin and opioids, UKH-1114 causes no motor impairment to animals.

The next step is to show that UKH-1114 is safe and nonaddictive in humans, which could take years. Once approved, the drug would be orally administered to patients.

Martin and Sahn are currently working on securing funding for further testing in the clinic.

In the future, Sahn said they want to better understand the mechanism of the sigma-2 receptor in pain relief and study whether targeting it can alleviate pain from osteoarthritis, fibromyalgia and other conditions.

“There is much to do, but we are eagerly looking forward to solving these problems and to discovering a new way to improve the quality of life for millions of pain sufferers,” Martin said.