Reduce brain pain

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Four Chinese characters in calligraphy—寧靜致遠 (ning jing zhi yuan) are framed on the wall of Yuanyuan “Kevin” Liu’s office. Words from ancient Chinese literature became Liu’s motto. Translated into English, they say that great achievements are not achieved by pursuing fame and fortune, but by devoting oneself to one’s calling.

Liu discovered his calling for neuroscience as an intern at the Institute of Neuroscience in China. His interest was sparked by his mentor at the time. “He would say to you, ‘Neuroscience is a subject where a brain studies a brain; that’s why it’s so special,” says Liu. “I was so fascinated by science that I decided to devote myself to this field, and now it is my career.”

Liu, who recently joined NIDCR as a tenure-track researcher for Earl Stadtman, studies a bundle of nerves called the corticospinal tract, which originates in the outer layers of the brain (cortex) and projects into the spinal cord. . The corticospinal tract is well known for carrying signals that govern voluntary movements like walking and fine motor skills like grasping in monkeys and humans. But Liu’s research reveals that the tract controls more than movement, it also appears to regulate the body’s pain signals. These findings, Liu says, “could open up possibilities for how we might manipulate our minds to control pain. Imagine volume control for pain.

Liu’s first insight into a broader role for the corticospinal tract came during his postdoctoral studies at Boston Children’s Hospital of Harvard Medical School. In monkeys and humans, nerves from the corticospinal tract project to an area in front of the spinal cord called the ventral horn, which relays signals to skeletal muscles to initiate movement. But in recent decades, scientists have discovered that certain corticospinal nerves also project to the dorsal horn of the spinal cord, which receives information about touch and sensation from the body. These projections are common to all mammals. Liu wondered why part of a so-called motor apparatus was projecting into a sensory region. Could this mean that the tract also plays a role in sensation?

Upon further investigation, Liu found out that was the case. His research has shown that mice with impaired corticospinal projections to the dorsal horn have reduced responses to light touch. These animals are slow to detect tape stuck to their paws and they are less sensitive to gentle brush strokes. By tracing signals in nerve fibers, Liu confirmed that tactile signals travel through nerves in the spinal cord and activate corticospinal neurons in the brain, which then relay messages back to the spinal cord. This back and forth between the brain and the spinal cord amplifies incoming light tactile sensations.

Liu and his colleagues also found that this bundle of nerves plays a crucial role in mechanical allodynia, neuropathic pain where light touch is perceived as painful. For people with mechanical allodynia, simple tasks like changing clothes can be difficult due to the pain triggered by the friction of the tissue against the skin. Liu’s team showed that eliminating certain corticospinal neurons alleviated mechanical allodynia in animal models.

According to Liu, these results open up new possibilities for the treatment of mechanical allodynia and other types of neuropathic pain, such as trigeminal neuralgia, which is caused by damaged or irritated facial nerves.

At NIDCR, Liu continues her work on the corticospinal tract and other neural pathways to better understand the brain’s mechanisms for perceiving sensory information. His lab at NIDCR focuses on two-way communication between mind and body, deciphering how the body sends sensory information to the brain and how the mind controls pain. For example, in life or death situations, the brain temporarily excludes pain from injury to help us survive. Liu wants to know how our mental state can amplify or suppress the perception of sensation, which can help uncover potential targets for pain treatment.

“As a scientist, the idea that I could do something new in the world excites me every day,” Liu says. This kind of excitement can inspire new generations of scientists, as it did for Liu as a university mentee. As a mentor now himself, Liu draws on lessons learned from his mentors, as well as the teachings of Chinese philosopher Confucius, to guide young researchers in his lab.

“Confucius’ teaching is really about diversity, where everyone is unique and different,” Liu said. “He seeks strength and virtue in everyone to help them reach their full potential. I’m a big fan of that idea as a mentor.

References

Touch and sensitivity to tactile neuropathic pain are fixed by corticospinal projections. Liu Y, Latremoliere A, Li X, Zhang Z, Chen M, Wang X, Fang C, Zhu J, Alexandre C, Gao Z, Chen B, Ding X, Zhou JY, Zhang Y, Chen C, Wang KH, Woolf CJ , He Z. Nature. 2018 Sep;561(7724):547-550. doi: 10.1038/s41586-018-0515-2. Published online September 12, 2018. PMID: 30209395; PMCID: PMC6163083.

Deconstruction of corticospinal circuits for goal-directed motor skills. Wang X, Liu Y, Li X, Zhang Z, Yang H, Zhang Y, Williams PR, Alwahab NSA, Kapur K, Yu B, Zhang Y, Chen M, Ding H, Gerfen CR, Wang KH, He Z. Cell. 2017 Oct 5;171(2):440-455.e14. doi:10.1016/j.cell.2017.08.014. Published online September 21, 2017. PMID: 28942925; PMCID: PMC5679421.

“Dialing Down Brain Pain was originally published by the National Institute of Dental and Craniofacial Research.”

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