Killing Pain by Killing Neurons

Researchers have found a new approach to treating chronic pain: destroy a small group of pivotal spinal cord nerve cells with a chemical "smart bomb." The treatment makes rats less sensitive to pain, according to a study in the current issue of Science. If the strategy works in humans, it could become an alternative to morphine.

Chronic pain is associated with a range of diseases and injuries, but its cause is often quite mysterious. Sufferers can experience intense, unrelenting pain long after the original source--tissue damage, for instance--appears to have healed. Often, the pain is aggravated by innocuous stimuli, such as the pressure of a blanket or even a gentle breeze against the skin.

Previous research had indicated, however, that spinal cord neurons that communicate using a neurotransmitter called substance P play a role in chronic pain. So neurobiologist Patrick Mantyh and his colleagues at the University of Minnesota and the Veterans Affairs Medical Center in Minneapolis devised a way to kill off only these neurons in rats. They attached to substance P a saporin, a toxin that brings the cell's protein-assembling ribosomes to a halt. Then they infused the hybrid molecule into the spinal cords of rats. Nerve cells that normally bind substance P also took in the complex--and died after the toxin took out their ribosomes.

To see if this would defeat chronic pain, the team induced the condition in rats. Even slight pressure on the paws would cause the animals to jerk them back--a response that mostly disappeared in rats given the substance P-saporin complex. Yet, the rats still reacted to truly painful stimuli, a response that could be dampened with morphine. That's important, says Mantyh, because doctors are unlikely to advise their patients to undergo this kind of treatment if it were to render morphine, their best painkiller, ineffective.

"These are very important experiments," says Tony Yaksh of the University of California, San Diego, who looks forward to any new approach for treating patients with cancer, arthritis, or other diseases associated with chronic pain. Before the technique hits the clinics, however, Mantyh's team must look for side effects and test the therapy in larger animals before proceeding to human tests. Eventually, Mantyh says, perhaps the treatment would employ a chemical that stuns rather than destroys the neurons.