Scientists from the University of Berne in Switzerland have identified a mechanism in the brain they believe is responsible for chronic pain — a discovery they hope will lead toward new treatments for chronic pain.
The findings from the research are published in the journal Neuron.
“The constant perception of pain severely influences the quality of life of the patients and represents an extraordinary emotional burden,” says lead author Dr. Thomas Nevian from the Department of Physiology at the University of Bern.
Chronic pain a leading cause of disability nationwide, affecting about 100 million Americans — more than cancer, diabetes, and heart disease combined. Despite the prevalence of chronic pain, proper treatment strategies are missing in many cases, says Dr. Nevian. This is in part because the etiology of chronic pain remains poorly understood.
“Thus,” he says, “understanding the development of chronic pain is of utmost importance for neuroscience research.”
Neurons in the gyrus cinguli create a ‘pain memory’
Through their research, Dr. Nevian and colleagues’ identified a cellular mechanism in a brain region called the gyrus cinguli, which is typically associated with the emotional aspects of pain. In a mouse model, the researchers found that neurons in this region are modified by chronic pain, establishing a form of “pain memory.”
“The neurons are constantly activated by a noxious stimulus,” explains Dr. Nevian, “thus building a memory trace for pain that becomes irreversible. Our idea was to understand this mechanism better to derive potential new treatment strategies.”
Because pain is perceived by electrical impulses in neurons, the researchers looked for electrical fluctuations among neurons in the limbic system. They found such changes – “more excitable” neurons – in the gyrus cinguli.
They believe that the neurons were more excitable here due to a down-regulation of an ion channel, which instead of regulating electrical properties of cells, leads to an increased number of nerve impulses in these cells. The increase in nerve impulses is therefore perceived by the brain as pain.
Next, the researchers attempted to restore the function of the ion channel. They succeeded in doing this by activating a receptor sensitive to serotonin. Dr. Nevian explains the role serotonin plays in reactivating the ion channel:
“It has been known for some time that serotonin can modulate pain perception and the function of some drugs is based on this. Nevertheless, what is new in our study now is that we were able to identify a specific subtype of serotonin receptor that reduced the perception of pain more efficiently. This is an important result, which might help to treat chronic pain more efficiently in the future.”
An interesting additional finding of this research is that the results suggest a mechanism to explain how tricyclic antidepressants work. Previously, it has been assumed that tricyclics work by acting on the spinal cord, but the new study shows that they also work directly on pain perception in the brain.
However, as the researchers pointed out, even though the findings are an “important step forward”, it will likely be some time before novel drugs are designed based on these results.
In related research, scientists from Saint Louis University and the National Institutes of Health recently discovered an “off-switch” for chronic neuropathic pain (pain resulting from nerve damage) in the form of a receptor in the brain called A3. When activated, the receptor halted or reversed chronic pain in rodents, indicating that a drug targeting A3 — which already exists — could be effective in treating some types of chronic pain.