With the opioid epidemic seemingly getting worse, researchers are working toward an addiction-free pain relief alternative.
A research team from the University of Virginia has discovered an enzyme called diacylglycerol lipase-beta (DAGLβ) that “chews up” fat molecules to produces chemical signals that control inflammation.
After identifying the enzyme as a possible drug target to reduce pain, the researchers found that selective molecules inhibit DAGLβ and reduce inflammation, similar to how aspirin and other non-steroidal anti-inflammatory drugs (NSAIDS) work.
However, in preclinical models, DAGLβ inhibitors provided pain relief without gastrointestinal toxicity when used over a long period of time, unlike NSAIDS. The researchers also found that DAGLβ inhibitors do not exhibit the addictive properties that opioids do.
“This could be a new route to treating long-term inflammation and pain without the side effects of toxicity and risk of addiction observed with current treatment options,” Ken Hsu, a chemistry professor at the University of Virginia, said in a statement. “Generally, if we block inflammation, we also affect the immune response. But we’re suggesting a different approach, one where we can stop inflammation without impacting the normal immune response.”
The researchers found in previous studies that were conducted in collaboration with researchers from Virginia Commonwealth University that DAGLβ inhibitors are highly effective at reducing different pain states, such as neuropathic pain and chemotherapy-induced peripheral neuropathy.
In the new study, the researchers discovered a new role for the enzyme in dendritic cells, a specialized type of innate immune cell that controls inflammation and activates the body’s infection fighting ability by stimulating T cells to produce an immune response.
Vaccination shows that the enzyme disruption does not affect dendritic cells immunogenic function in vivo while regulating lipopolysaccharide-stimulated tumor necrosis factor alpha response of primary dendritic cells. The enzyme also uncouples cytokine response and the CD8 + T cell priming capacity of dendritic cells.
“We found that by blocking DAGLβ, we can stop inflammation without affecting immunity,” Hsu said. “This supports the idea that DAGLβ is a viable target for long-term blockade of inflammation and pain without potentially compromising our immune system.”
According to the National Institute on Drug Abuse, 1.7 million people in the U.S. suffer from substance abuse disorders related to opioid use for pain relief, resulting in a $78 billion annual economic burden in health care and addiction treatment costs, lost worker productivity and increased criminal activity. More than 47,000 people in 2017 died due to drug abuse involving opioids or related drugs.
The study was published in Cell Chemical Biology.
Filed Under: Drug Discovery and Development
