Lasting Relief for Chronic Pain

For people living with chronic pain, lasting relief can feel out of reach. Now, University at Buffalo researchers may have opened up a new frontier of treatment: a non-opioid molecule that eases pain for up to three weeks, delivered in a single injection.

Like the numbing sensation we’re all familiar with when we get anesthetized at the dentist’s office, the new molecule developed at UB acts like a local anesthetic, but in a much more targeted way.

“Local anesthetics dramatically changed health care when first introduced into clinical practice during the turn of the 20th century,” noted Arindam Bhattacharjee, professor of pharmacology and toxicology at UB, and senior author of preclinical studies on the new molecule reported recently in the journal Pain.

But as Bhattacharjee explained, there are limitations with local anesthetics. They aren’t very selective for pain fibers—meaning they numb the whole area—and they don’t last long.

The new molecule targets a protein called Magi-1, a scaffolding protein that brings specific proteins together at precise locations within the cell membrane. One of the proteins it interacts with is NaV1.8, an ion channel that plays an important role in transmitting pain.

Earlier this year, Bhattacharjee pointed out, the Food and Drug Administration approved a drug that blocks the NaV1.8 ion channels to treat acute pain.

“This was a breakthrough because a new pain-targeted drug had not been developed for many years,” he said. “Unfortunately, that drug seems to only work for acute, post-surgical pain. It has yet to show success for chronic pain.”

The new molecule addresses pain through a different approach: Instead of blocking the pain-transmitting NaV1.8 ion channels, it targets the interaction they have with the Magi-1 scaffolding protein.

The team’s new molecule is a lipidated peptide (a peptide modified with lipid molecules), and it acts like a “decoy” peptide that outcompetes NaV1.8 channels in binding to Magi-1. When NaV1.8 channels can’t bind to Magi-1, Bhattacharjee explained, they become degraded. And once degraded, they can’t function properly to transmit pain.

Since it takes weeks to clear the lipidated peptide, the researchers saw weeks of pain relief.

The next step for the team is to begin toxicity trials. “Since we are locally injecting the peptide, we believe toxicity will be minimal,” said Bhattacharjee.

Then it’s on to clinical trials, and, ultimately, using the lipidated peptide to treat chronic pain in people and bring lasting relief.