Researchers developing nonopioid drug for chronic pain—but is this the right approach?
Researchers from the Virginia Tech School of Neuroscience, in collaboration with the University of California San Diego and the U.S. National Institutes of Heath (NIH), are in the early stages of developing a drug that can treat certain types of chronic pain without the addictive consequences of opioids, according to a recent article published in The Journal of the International Association for the Study of Pain.
The drug compound, known as ML351, was discovered by researchers from the NIH and is designed to inhibit the naturally-produced enzyme 15-Lipoxygenase-1, which synthesizes bioactive lipids that contribute directly to chronic pain not relieved by common over-the-counter nonsteroidal anti-inflammatory drugs (NSAIDs) such as ibuprofen. This lack of relief can lead patients to resort to more powerful drugs including opioids such as Oxycodone and other narcotics, the researchers say in the report.
"Our goal is to demonstrate the preclinical efficacy of ML351 for chronic pain that does not respond to nonsteroidal anti-inflammatory drugs and might otherwise be treated with opioids," said Ann Gregus, PhD, a research scientist with the School of Neuroscience.
Gregus is working on the drug compound with Matt Buczynski, PhD, an assistant professor of neuroscience who specializes in drug addiction. Acute pain that occurs from touching a hot stove helps protect us from severe self-injury, but chronic activation of these pain signaling pathways can be debilitating, he said.
Only a limited number of drugs exist for effectively treating chronic pain, such as pain caused by autoimmune diseases, said Buczynski. Current anti-inflammatory drugs such as NSAIDs and steroids help relieve pain by reducing inflammation, but for many types of chronic pain they are less effective.
ML351 targets a novel signaling pathway believed to be responsible for the development of chronic pain that does not respond to anti-inflammatory drugs. ML351 may be effective for multiple types of pain, and our future studies will investigate its utility in other models of chronic pain, said Gregus.
Treatment for unmanaged pain is the primary motivation for seeking medical care, Buczynski said. Issues with chronic pain affect more than 40 percent of the U.S. population, resulting in costs exceeding $100 billion per year. The misuse of pain killers has contributed to the ongoing opioid crisis, which was declared a National Public Health Emergency in 2016. The problem has grown so wide that fatal overdoses from opioid use are now the leading cause of unnatural death, and some of the highest per capita opioid abuse in the country occurs in rural western Virginia, where Virginia Tech is based.
"Chronic pain is extremely challenging to treat due to a lack of effective first-line therapies," Buczynski said. "While opioids are highly effective medications, concerns regarding danger of their misuse have reached a fever pitch.”
The need for a nonopioid, non-addictive pain medication is paramount, said Gregus.
"Serious issues with long-term usage or misuse and diversion of opioids necessitate the development of alternative treatments to expand the options available to patients with chronic pain," she said. "ML351 shows promise as a non-opioid therapeutic to treat pain states not relieved by over-the-counter medications. Future studies will determine how we can translate these findings into novel therapeutics for clinical use."
However, some integrative professionals say this approach ignores the root cause of chronic pain and oversimplifies the complexity of pain management and addiction. Integrative therapies including nutrition, chiropractic, massage, Traditional Chinese Medicine, yoga, movement, relaxation, and stress management help patients develop coping skills and resiliency and address the precise cause or causes of their pain, whereas this potential drug offers nothing more than a “quick fix”.
It will be several years before the drug enters clinical trials in humans, much less reaches pharmacy shelves. For now, Gregus and her team will continue to test ML351 in other animal models.
"The next step is to evaluate its effectiveness in reversing established pain states of arthritis or diabetic neuropathy," Gregus added. "If this target has broad applicability for treating pain states, the compound can be optimized chemically and tested for safety and efficacy in larger animal species and then humans."
Editor’s note: This is a developing story. We invite members of the integrative healthcare community to comment by e-mailing editor Katherine Rushlau at [email protected].