November 29, 2023

On a Mission To Alleviate Chronic Pain: Finding the Brain’s “Off Switch” for Pain

Fan Wangs research studies of how the brain controls pain might one day cause new treatments that might help countless people. Credit: M. Scott Brauer
Fan Wangs research studies of how the brain manages pain might one day cause new treatments that could assist millions of people.
About 50 million Americans experience chronic discomfort, which interferes with their every day life, social interactions, and ability to work. MIT Professor Fan Wang desires to develop brand-new methods to help ease that discomfort, by studying and potentially customizing the brains own pain control mechanisms.
Her recent work has actually recognized an “off switch” for discomfort, situated in the brains amygdala. She hopes that discovering ways to control this switch might cause new treatments for persistent pain.

Individuals are more anxious, and they look for drugs to reduce such mental pain,” Wang says. Utilizing this technique in mice, she identified neurons that become active in action to discomfort, but so lots of nerve cells across the brain were activated that it didnt provide much useful details. As a way to indirectly get at how the brain manages discomfort, she chose to utilize CANE to explore the results of drugs utilized for basic anesthesia. Throughout basic anesthesia, drugs render a patient unconscious, but Wang assumed that the drugs may likewise shut off discomfort understanding.
They likewise are measuring the neurons electrical activity and how they connect with other nerve cells in the brain, in hopes of determining circuits that could be targeted to tamp down the perception of discomfort.

” Chronic discomfort is a major social issue,” Wang says. “By studying pain-suppression nerve cells in the brains main amygdala, I wish to produce a new therapeutic approach for easing discomfort.”
Wang, who joined the MIT faculty in January 2021, is likewise the leader of a new initiative at the McGovern Institute for Brain Research that is studying drug addiction, with the goal of developing more reliable treatments for dependency.
” Opioid prescription for persistent pain is a major factor to the opioid epidemic. Individuals are more anxious, and they look for drugs to reduce such mental discomfort,” Wang states.
Sensory circuits
Wang, who grew up in Beijing, explains herself as “a nerdy kid” who liked books and mathematics. In high school, she took part in science competitors, then went on to study biology at Tsinghua University.
After completing her PhD, Wang decided to change gears. As a postdoc at the University of California at San Francisco and after that Stanford University, she began studying how the brain perceives touch.
In 2003, Wang joined the professors at Duke University School of Medicine. There, she started developing methods to study the brain circuits that underlie the sense of touch, tracing circuits that bring sensory information from the whiskers of mice to the brain. She also studied how the brain incorporates movements of touch organs with signals of sensory stimuli to produce perception (such as using extending movements to pick up elasticity).
As she pursued her sensory understanding studies, Wang ended up being thinking about studying pain understanding, however she felt she needed to develop new methods to tackle it. While at Duke, she developed a technique called CANE (recording triggered neural ensembles), which can recognize networks of neurons that are activated by a specific stimulus.
Utilizing this approach in mice, she identified nerve cells that end up being active in response to pain, however many nerve cells across the brain were triggered that it didnt provide much helpful information. As a method to indirectly get at how the brain manages discomfort, she decided to utilize CANE to check out the impacts of substance abuse for basic anesthesia. Throughout general anesthesia, drugs render a client unconscious, however Wang assumed that the drugs may also turn off pain perception.
” At that time, it was just a wild idea,” Wang remembers. “I believed there might be other systems– that rather of just a loss of consciousness, anesthetics may do something to the brain that in fact turns discomfort off.”
Support for the existence of an “off switch” for pain came from the observation that wounded soldiers on a battleground can continue to fight, essentially shutting out discomfort in spite of their injuries.
In a study of mice treated with anesthesia drugs, Wang discovered that the brain does have this kind of switch, in an unforeseen location: the amygdala, which is included in managing emotion. She showed that this cluster of nerve cells can switch off discomfort when triggered, and when it is reduced, mice end up being highly conscious normal gentle touch.
” Theres a baseline level of activity that makes the animals feel regular, and when you trigger these nerve cells, theyll feel less pain When you silence them, theyll feel more pain,” Wang states.
Switching off pain.
That finding, which Wang reported in 2020, raised the possibility of in some way regulating that switch in human beings to try to treat chronic discomfort. They also are determining the nerve cells electrical activity and how they communicate with other nerve cells in the brain, in hopes of determining circuits that could be targeted to tamp down the perception of pain.
One way of regulating these circuits might be to utilize deep brain stimulation, which involves implanting electrodes in particular areas of the brain. Focused ultrasound, which is still in early stages of advancement and does not need surgical treatment, might be a less intrusive option.
Another approach Wang has an interest in exploring is combining brain stimulation with a context such as taking a look at a smartphone app. This kind of pairing might help train the brain to shut off discomfort utilizing the app, without the requirement for the initial stimulation (deep brain stimulation or ultrasound).
” Maybe you do not require to constantly stimulate the brain. You may just require to reactivate it with a context,” Wang says. “After a while, you would most likely need to be restimulated, or reconditioned, however at least you have a longer window where you do not require to go to the medical facility for stimulation, and you just need to utilize a context.”
Wang, who was drawn to MIT in part by its focus on fostering interdisciplinary partnerships, is now dealing with a number of other McGovern Institute members who are taking various angles to try to figure out how the brain generates the state of craving that occurs in drug addiction, consisting of opioid addiction.
“Were going to concentrate on trying to understand this craving state: how its developed in the brain and how can we arrange of remove that trace in the brain, or at least control it. And after that you can neuromodulate it in genuine time, for instance, and provide people a possibility to get back their control,” she states.