Getting ahead of neuropathic pain

by Bruce Sylvester – Researchers at Boston Children’s Hospital and the Massachusetts Institute of Technology report the discovery a potential method to delay the onset of neuropathic pain.

Lead investigators Daniel Kohane, MD, PhD, of Boston Children’s Department of Anesthesia and Robert Langer, ScD, of MIT, reported the results of animal studies online on October 8 in the Proceedings of the National Academy of Sciences.

“Currently neuropathic pain is treated with systemic medications, but there has been significant interest in using powerful local anesthetics to block aberrant nerve discharges from the site of injury to prevent the onset of neuropathic pain,” said Kohane. “Others have tried with varying degrees of success to do this in animal models using a variety of methods, but if applied clinically, those methods would require surgical intervention or could be toxic to tissues. We want to avoid both of those concerns.”

The researchers combined saxitoxin, a local anesthetic, with dexamethasone, which prolongs the effects of saxitoxin effects. The drugs were enclosed in liposomes, lipid spheres about 5.5 micrometers wide, for delivery to the site of nerve or tissue damage.

The researchers attempted to use this method to block the onset of neuropathy in an animal model of sciatic nerve injury.

They reported that one injection delayed onset of neuropathic pain by about two days compared to no treatment. Three injections at the site of injury over the course of 12 days delayed onset of pain by about a month.

The treatment also appeared to prevent reprogramming of the central nervous system. The investigators noted that astrocytes in the spine showed no pain-related activation at 5 days and 60 days after injury in animals treated with the injections.

“Ultimately we’d like to develop a way to reversibly block nerve signaling for a month with a single injection without causing additional nerve damage,” Kohane explained. “For the moment, we’re trying to refine our methods so that we can get individual injections to last longer and figure out how to generalize the method to other models of neuropathic pain.

“We also need to see whether it is safe to block nerve activity in this way for this long,” he continued. “We don’t want to inadvertently trade one problem for another. But we think that this approach could be fruitful for preventing and treating what is really a horrible condition.”