Scientists have identified a small area in the brains of mice that is capable of turning pain off, which may one day lead to the development of drug therapies and treatments meant to target pain.
The newly dubbed CeAga is a large mass of neurons located in the amygdala of mice. In humans, this part of the brain is believed to be responsible for emotions and responses like fight-or-flight or general anxiety. Though the amygdala is larger in mouse brains, the researchers believe their findings likely translate to humans as well.
"People do believe there is a central place to relieve pain, that's why placebos work," said senior author Fan Wang, the Morris N. Broad Distinguished Professor of neurobiology in the School of Medicine, in a statement. "The question is where in the brain is the center that can turn off pain."
Wang adds that previous studies have largely focused on areas of the brain that are activated by pain.
"But there are so many regions processing pain, you'd have to turn them all off to stop pain. Whereas this one center can turn off the pain by itself,” said Wang.
The research builds on previous work that determined which brain neurons are activated by general anesthetics. When under anesthesia, the scientists found that a part of the brain known as the supraoptic nucleus located at the base of the brain in the hypothalamus promotes slow-wave sleep. General anesthesia was also shown to activate the subset of inhibitory neurons now known as CeAga.
Publishing their work in Nature Neuroscience, scientists at Duke University mapped out the areas of the brain that were active in mice when they experienced pain. Once identified, the researchers then used a technology called optogenetics to activate a small population of cells in the brain. Optogenetics uses light to target and control specific neurons in the brain that are genetically modified to be light sensitive. When triggered by light, these areas of the brain may turn off or on.
"Pain is a complicated brain response," Wang said. "It involves sensory discrimination, emotion, and autonomic (involuntary nervous system) responses. Treating pain by dampening all of these brain processes in many areas is very difficult to achieve. But activating a key node that naturally sends inhibitory signals to these pain-processing regions would be more robust."
At least 16 brain centers were shown to receive input from the CeAga. When experiencing pain, a mouse will typically lick its paw or wipe at its face. However, when these parts of the brain were “turned off”, test mice did not exhibit any such behaviors.
"It's so drastic," Wang said. "They just instantaneously stop licking and rubbing."
Next, the researchers plan to sequence associated cells in an attempt to identify a specific gene responsible for the activation of neurons.