Discovery points to novel pain-control strategy

It may be possible to turn down pain signals at the source

While it’s not yet a practical answer for chronic pain, a discovery announced Sept. 29 by researchers at The University of Texas Health Science Center at San Antonio holds out hope for a novel, safe and effective way to control pain at its source.

If translated into a therapy, this approach would be completely different from current pain-control methods, which frequently lead to addiction and overdoses, said Mark S. Shapiro, Ph.D., professor of physiology in the School of Medicine at the Health Science Center.

Pain therapy could even be tailored to each patient using the strategy. Dr. Shapiro is senior author of the research, which is reported in the journal, Neuron.

How would the new approach work? Charged salt atoms (called ions) such as calcium and sodium pass in and out of cells through protein pores called ion channels. The Health Science Center 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 heat or cold.

“One ion channel we studied, called TRPV1, starts the signal that tells the brain something hurts,” Dr. Shapiro 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. We observed that proteins of these ion channels interact with each other and function in tandem, which isn’t supposed to happen because it was thought that those two processes occurred in different parts of the neuron.”

Ion channels are in the outer membranes of all cells including neurons, the cells of the nervous system. The finding that these two ion channels are coupled has important implications for all neurons. This includes both sympathetic neurons, which control autonomic 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 ramifications for pain control are especially exciting to Dr. Shapiro and his colleagues.

“The most unexpected, exciting and provocative result of this work,” he said, “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. 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 reinforcing pain cycle that is often so debilitating for people. 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 some 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, which is 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.”

Dr. Shapiro and his team used a technique called super-resolution microscopy, which gained worldwide acclaim in 2014 when three scientists shared the Nobel Prize in Chemistry for its discovery. This powerful approach enables scientists to see individual protein molecules with visible light at a resolution nearly 100 times greater than traditional approaches.



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