Scientists discover powerful potential pain reliever

August 16, 2017
Stephen Martin (left) and James Sahn have discovered a new pain reliever that acts on a previously unknown pain pathway. Credit: Stephen Martin

A team of scientists led by chemists Stephen Martin and James Sahn at The University of Texas at Austin have discovered what they say is a powerful pain reliever that acts on a previously unknown pain pathway. The synthetic compound, known as UKH-1114, is as effective at relieving neuropathic pain in injured mice as a drug widely used for pain relief called gabapentin, but it works at a much lower dose, with longer duration of action.

If the researchers can demonstrate that the drug is safe, effective and nonaddictive in humans—a process that typically takes years—the discovery could be instrumental in addressing one of today's biggest public health challenges: the opioid abuse epidemic.

Nearly a third of Americans suffer from chronic pain, yet the most effective pain relievers—opioids—are addictive and often require increased dosing to maintain efficacy. According to the National Institute on Drug Abuse, about 2 million people in the U.S. suffer from addiction to prescription opioid pain relievers. Alternatives to opioids have their own drawbacks—for example, gabapentin (sold as Neurontin) can cause cognitive impairment in certain individuals.

"This opens the door to having a new treatment for neuropathic pain that is not an opioid," said Martin, a professor and the M. June and J. Virgil Waggoner Regents Chair in Chemistry. "And that has huge implications."

The pain drug they found binds to a receptor on cells throughout the central nervous system called the sigma 2 receptor. Although it was discovered 25 years ago, scientists still did not know what sigma 2 did until now.

Theodore Price, associate professor of neuroscience at The University of Texas at Dallas and a leading expert on chronic pain, tested UKH-1114 on mice with nerve damage and found that it alleviated pain as well as gabapentin did, but at a much lower dose (one-sixth as much) and was effective much longer (lasting for a couple of days, compared with 4 to 6 hours). This research is the first to demonstrate that the sigma 2 receptor may be a target for treating neuropathic pain.

Results are published in the Aug. 18 print edition of the journal ACS Chemical Neuroscience. An earlier paper, published online on May 28 in the journal Proceedings of the National Academy of Sciences, described the molecular cloning and identification of the sigma 2 receptor.

The researchers have filed patent applications on the new compound.

Neuropathic , or , is caused when nerves in the central nervous system are damaged. Among other things, it can result from chemotherapy, diabetes and injuries to the brain or spinal cord.

Much work remains to be done before UKH-1114 can enter the market. More studies are needed to demonstrate safety, efficacy and oral bioavailability. In the meantime, the scientists are working to understand, on a fundamental level, how activating the sigma 2 receptor relieves .

Still, Martin and Sahn are excited by the compelling results from the mouse model.

"We started out just working on fundamental chemistry in the lab," said Sahn, a research scientist in the Department of Chemistry. "But now we see the possibility that our discoveries could improve the quality of people's lives. That is very satisfying."

Explore further: Are clinicians overprescribing gabapentinoids for pain?

More information: James J. Sahn et al, Sigma 2 Receptor/Tmem97 Agonists Produce Long Lasting Antineuropathic Pain Effects in Mice, ACS Chemical Neuroscience (2017). DOI: 10.1021/acschemneuro.7b00200

Assaf Alon et al. Identification of the gene that codes for the σ2receptor, Proceedings of the National Academy of Sciences (2017). DOI: 10.1073/pnas.1705154114

Related Stories

Are clinicians overprescribing gabapentinoids for pain?

August 3, 2017
(HealthDay)—Clinicians may be overprescribing gabapentinoids, in part as a response to the opioid epidemic, according to a perspective piece published in the Aug. 3 issue of the New England Journal of Medicine.

Scientists discover new category of analgesic drugs that may treat neuropathic pain

March 29, 2017
New research published online in The FASEB Journal suggests that a novel therapeutic target called LPCAT2 may prove effective against pain that is not receptive to the current treatments. This study has also revealed the ...

Potential drug for treating chronic pain with few side effects

July 31, 2017
Researchers at Okayama University describe in the Proceedings of the National Academy of Sciences the effect of clodronate on the regulation of adenosine triphosphate release and its potential as a drug for the treatment ...

Investigators examine the relationship between pain and opioid abuse

June 12, 2017
The drug overdose epidemic is largely driven by opioids, which continue to be prescribed for chronic pain despite recommendations to use non-opioids for most cases. A new review published in the British Journal of Pharmacology ...

Targeting brain cells to alleviate neuropathic pain

August 8, 2016
Neuropathic pain – which affects more than 1 million Americans – could be reduced or even eliminated by targeting brain cells that are supposed to provide immunity but, in some instances, do the opposite, causing chronic ...

Recommended for you

Investigating patterns of degeneration in Alzheimer's disease

November 17, 2017
Alzheimer's disease (AD) is known to cause memory loss and cognitive decline, but other functions of the brain can remain intact. The reasons cells in some brain regions degenerate while others are protected is largely unknown. ...

Study may point to new treatment approach for ASD

November 17, 2017
Using sophisticated genome mining and gene manipulation techniques, researchers at Vanderbilt University Medical Center (VUMC) have solved a mystery that could lead to a new treatment approach for autism spectrum disorder ...

Paraplegic rats walk and regain feeling after stem cell treatment

November 16, 2017
Engineered tissue containing human stem cells has allowed paraplegic rats to walk independently and regain sensory perception. The implanted rats also show some degree of healing in their spinal cords. The research, published ...

Brain implant tested in human patients found to improve memory recall

November 15, 2017
(Medical Xpress)—A team of researchers with the University of Southern California and the Wake Forest School of Medicine has conducted experiments involving implanting electrodes into the brains of human volunteers to see ...

Researchers identify potential mediator for social memory formation

November 15, 2017
Research by a group of scientists at the Department of Physiology, Yong Loo Lin School of Medicine, National University of Singapore (NUS Medicine) have discovered that a tiny brain region plays a critical role in the formation ...

Improving clinical trials with machine learning

November 15, 2017
Machine learning could improve our ability to determine whether a new drug works in the brain, potentially enabling researchers to detect drug effects that would be missed entirely by conventional statistical tests, finds ...

2 comments

Adjust slider to filter visible comments by rank

Display comments: newest first

jdman
not rated yet Aug 21, 2017
Need some test subjects?
SKULLTRAP
not rated yet Aug 21, 2017
If this new drug cannot produce a euphoric state, shut the research down. Waste of time & $$.

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.