Painkillers are currently used to treat a number of different pain conditions, but everyone knows they are far from a perfect solution. Traditional opioids carry a high risk of addiction and overdose, which is why researchers are so keen on finding another way to calm irritated nerves and help block nerve signals. With the help of nanoparticles, they may do just that.

According to an international team of researchers, we may soon be able to use nanoparticles to deliver drugs into specific compartments of nerve cells, allowing us to better treat pain while also reducing the risk of dependency that comes with traditional opioids. Researchers said the nanoparticle delivery method has proven successful in rats and mice, and they hope to improve the science so the results are replicable in humans.

“We have taken a drug—an FDA-approved anti-vomiting medication—and using a novel delivery method, improved its efficacy and duration of action in animal models of inflammatory pain and neuropathic pain,” said Nigel Bunnett, PhD, chair of the Department of Basic Science and Craniofacial Biology at New York University (NYU) College of Dentistry and the study’s senior author. “The discovery that nanoparticle encapsulation enhances and prolongs pain relief in laboratory animals provides opportunities for developing much-needed non-opioid therapies for pain.”

Nanoparticle Delivery

The team of researchers began by studying a family of proteins called G protein-coupled receptors, which are an area that are targeted by roughly one-third of clinically used drugs. The standard line of thinking was that these receptors function at the surface of nerve cells, but the team discovered that when activated, the cells moved within a compartment called the endosome. Inside the endosome, the receptors continue to function for prolonged periods, and this activity is what drives pain perception.

In their study, researchers narrowed their focus on a G protein couple receptor called the neurokinin 1 receptor.

“Major pharmaceutical companies had programs to develop neurokinin receptor antagonists for chronic diseases, including pain and depression. However, in human trials, things fell apart,” said Bunnett. “The neurokinin receptor is the poster child for failures in drug discovery to treat pain.”

Researchers believed that those drugs failed to provide relief because they were designed to block pain receptors at the surface level of the cells, not in the endosomes. But by turning to nanoparticles, researchers can deliver a neurokinin receptor blocker called aprepitant, which is an FDA-approved drug that is used to prevent nausea and vomiting. Essentially, these nanoparticles enter the nerves that transmit pain signals and release the neurokinin receptor blocker, halting pain. In clinical trials involving mice and rats, pain completely resolved or resolved for longer periods compared to opioids and other traditional treatments. By using this technology, it also minimizes the dosage needed, which can help to prevent traditional side effects.

Researchers hope that these results can be mimicked in clinical trials involving humans, and they hope to further their understanding by eventually only targeting the nerve cells that sense pain, as this would lead to even smaller doses. Hopefully they are successful, because we can always use more effective and less dangerous ways of controlling chronic pain.