Potential pain treatment’s mechanism deciphered

Scientists think they have a new understanding of a potential long-lasting, targeted treatment for chronic pain.

When injected into the spinal cord of a mouse with nerve damage, cells extracted from mouse bone marrow flock to injured cells and produce a pain-relieving protein, researchers report July 13 in the Journal of Clinical Investigation. The results may lead to better chronic pain treatments in humans.   

The specialized cells homed in on their ultimate destination by following chemical signals released by the injured nerve cells. There, the injected cells produced an anti-inflammatory protein, called transforming growth factor beta 1 (TGFB1), which provided long-term pain relief. Researchers had known that the marrow cells relieved pain, but didn’t know how, says study coauthor Ru-Rong Ji, a neurobiologist at Duke University Medical Center.

“These cells make drugs at sites of injury,” says biologist Arnold Caplan of Case Western Reserve University in Cleveland. “They’re drugstores.”    

Ji and colleagues found that they could relieve chronic nerve pain in mice by injecting 250,000 cells or fewer into the narrow space under the spinal cord membrane. This site is protected by the blood-brain barrier, preventing immune attacks on the injected cells and allowing these cells to live longer, Ji says. Some clinical trials inject cells like these into the bloodstream, Caplan says, requiring the use of many more cells, many of which get stuck in the lungs and liver. 

The cells relieved pain in mice in less than one day. The effect lasted for over a month, whether the cells were administered at four or 21 days after nerve injury. A mouse’s pain was measured as increased sensitivity to touch and increased time spent in a chamber it had learned to associate with a pain-killing drug.

What works for mice may not work for humans, says research neuroepidemiologist John Farrar of the University of Pennsylvania. But these data could be used as the basis for a human clinical trial using human cells, Caplan says. Because cells injected into the spinal cord are protected against immune attacks, Ji believes that humans could receive cells from unrelated donors, or even different species.

Ji predicts that the cells could be engineered to make even more TGFB1. Other studies indicate that these drugstore cells produce pain-relieving compounds in addition to this particular protein, Caplan says.

Future research must determine if these treatments have unpredicted effects over time, Farrar says. TGFB1 is associated with cell growth, and losing control of this protein could cause injected cells to grow out of control and become cancerous. Ji says that cancer seemed to pose a small risk in this study: The injected cells never incorporated into spinal tissue, and they disappeared from the spine completely within three months.

“A lot more work needs to be done to understand what the long-term downsides would be,” Farrar says. But he says that the study is promising. “It’s very exciting that we should find a set of cells that we could inject that might make a difference.”