St. Louis, June 18, 1998 -- The brain can teach cells in the spinal cord to feel pain, scientists have discovered. Once receptors on these cells are activated, they continue to transmit pain signals even if there is no injury, so blocking them may lead to better treatments for persistent pain.
"Nerve fibers from the brain can help control pain, just like medications," explains Min Zhuo, Ph.D., assistant professor of anesthesiology and neurobiology at Washington University School of Medicine in St. Louis. "Now, we have shown that those fibers also can enhance the transmission between the painful stimulus and the neuron in the spinal cord."
The researchers report their findings in the June 18 issue of the journal Nature. The study was funded, in part, by a grant from the National Institute on Drug Abuse.
When we encounter a painful event, receptors on the skin, muscle or internal organs trigger an electrical impulse that travels along a nerve fiber to the dorsal horn of the spinal cord. That fiber connects with a nerve cell, which passes the pain signal up the spinal cord to the brain. Because the signals cross junctions -- synapses -- on their way to the brain, they can be modified en route. For example, opioids prevent signals from getting across synapses, thus preventing patients from feeling pain.
The brain also can block pain by preventing signals from crossing synapses. That may be why some soldiers can continue to fight even though they are gravely wounded. The investigators found that the brain also can enhance pain by activating silent synapses, however. A brain region called the rostroventral medulla (RVM) sends a chemical signal to cells in the dorsal horn of the spinal cord, they discovered. The neurotransmitter serotonin activates silent synapses in dorsal horn neurons.
Inefficient, or silent synapses were proposed more than 20 years ago, but technical limitations prevented detailed studies of how and why they are activated. Using whole cell patch-clamp recording techniques to monitor the electrical responses of individual neurons, Zhuo and colleagues found that after silent synapses are awakened, they tend to remain active and transmit pain signals.
These synapses can be activated by both strong pain signals and messages from the RVM. Zhuo found that spinal cord neurons, much like those in the brain's hippocampus, become more efficient at transmitting signals through a process called long-term potentiation (LTP).
LTP in the hippocampus is associated with learning and memory. Zhuo suggests that pain learning also is accomplished through LTP. After intense or persistent pain, dorsal horn neurons and the RVM learn to anticipate pain, and they continue to transmit pain signals back to the conscious part of the brain.
Just as we can't forget an old phone number or the truth about Santa Claus, silent synapses can't forget how to transmit pain, Zhuo says. Once activated by extreme or chronic pain, they remain open and transmit signals that either increase the severity of pain or the length of time we perceive it. That may be why cancer pain can persist, even after treatment.
"When you have a tumor, the several weeks or months of pain may induce a change in your pain response, so even after the tumor is removed, you're likely to continue to have pain," Zhuo says.
The good news is that silent synapses provide a potential target for pain blockers. As opioids and other drugs target normal pain pathways, other treatments might target these secondary pain pathways, interrupting the passage of inappropriate signals to the brain.
Journal
Nature