Zero pain

What if there were a safe and effective way to control pain at its source, tailored to each patient, yet without the risk of addiction and overdose?

Mark S. Shapiro, Ph.D., professor of physiology, said unexpected and provocative results from his research indicates this could someday become a reality.

The key lies in our ions. Charged salt atoms, or ions, such as calcium and sodium, pass in and out of cells through protein pores called ion channels. Dr. Shapiro and a team of researchers discovered that two ion channels in sensory nerve cells are interacting in unexpected ways. Sensory nerve cells are neurons that initiate the sensations of pain or burning.

“One ion channel we studied, called TRPV1, starts the signal that tells the brain something hurts,” he said. “The other channel, a calcium ion channel called CaV1.2, signals genes to turn on or off in response to activity, such as painful stimuli.”

The researchers saw that proteins of these ion channels interact with each other and function in tandem.

“It was thought that those two processes occurred in different parts of the neuron,” he said.

Ion channels are in the outer membranes of all cells, including neurons, the cells of the nervous system. The finding that these two channels are coupled has important implications for all neurons, including sympathetic neurons, which control automatic functions of the body such as heart rate and breathing, and sensory neurons, which sense painful stimuli and sound the alarm to the brain.

“The most unexpected, exciting and provocative result of this work is the discovery that the ion channel that starts the pain signal is intimately associated with the ion channel that turns on or off genes’ response. They are locked together,” he said. “It’s as if two people are in locked arms, and when one takes a step, the other moves in lockstep.”

The researchers will now study whether turning genes on or off can stop the pain cycle that is often so debilitating. It theoretically should be possible to reduce the association between the ion channels to lower the pain signal and remove such chronic pain. In individuals who have lost pain sensation in part of the body, such as in the feet, it might be possible to increase the signal. This would increase sensitivity to pain to help them avoid injuries such as burns or ulcers.

“All we have now are centrally acting opioid painkillers—fentanyl, hydrocodone and others—which has led to an epidemic of abuse and overdoses,” Dr. Shapiro said. “These medications don’t stop the pain signal but instead cover up the sensation in the brain, which frequently leads to devastating addiction. We want to treat pain at the source, at the sensory neuron, so that the pain signal never gets started in the first place, or if it does get started, doesn’t lead to this vicious cycle of pain and addiction.”

The results of his study were reported in the journal Neuron.