The way we perceive and respond to physical pain is more than just a physical sensation – it also carries an emotional weight. This emotional discomfort can motivate us to take action and helps us learn to associate negative feelings with situations so we can avoid them in the future. However, when our ability to tolerate pain becomes too sensitive or lasts too long, it can result in chronic and affective pain disorders such as fibromyalgia, migraines, and post-traumatic stress disorder (PTSD).

Researchers at the Salk Institute have now identified a brain circuit that gives physical pain its emotional tone. Published in the Proceedings of the National Academy of Sciences, the study reveals a group of neurons in the central brain area called the thalamus that appears to mediate the emotional or affective side of pain in mice.

The prevailing view for decades was that the brain processes sensory and emotional aspects of pain through separate pathways. However, this new pathway challenges the textbook understanding of how pain is processed in the brain and body. The physical sensation of pain allows you to immediately detect it, assess its intensity, and identify its source, while the affective part of pain makes it unpleasant.

This distinction is crucial because most people start to perceive pain at the same stimulus intensities. However, our ability to tolerate pain varies greatly, with some individuals being more sensitive than others. The affective processing determines how much we suffer or feel threatened by pain. If this becomes too sensitive or lasts too long, it can result in a pain disorder.

The researchers used advanced techniques to manipulate the activity of specific brain cells and discovered a new spinothalamic pathway in mice. In this circuit, pain signals are sent from the spinal cord into a different part of the thalamus, which has connections to the amygdala, the brain’s emotional processing center. This particular group of neurons can be identified by their expression of CGRP (calcitonin gene-related peptide).

When these CGRP neurons were “turned off,” the mice still reacted to mild pain stimuli but didn’t seem to associate lasting negative feelings with these situations. However, when these same neurons were “turned on,” the mice showed clear signs of distress and learned to avoid that area, even when no pain stimuli had been used.

“Pain processing is not just about nerves detecting pain; it’s about the brain deciding how much that pain matters,” says first author Sukjae Kang. Understanding the biology behind these two distinct processes will help us find treatments for the kinds of pain that don’t respond to traditional drugs.

Many chronic pain conditions, such as fibromyalgia and migraine, involve long, intense, unpleasant experiences of pain often without a clear physical source or injury. Some patients also report extreme sensitivity to ordinary stimuli like light, sound, or touch which others would not perceive as painful.

Han says overactivation of the CGRP spinothalamic pathway may contribute to these conditions by making the brain misinterpret or overreact to sensory inputs. In fact, transcriptomic analysis of the CGRP neurons showed that they express many of the genes associated with migraine and other pain disorders.

Several CGRP blockers are already being used to treat migraines. This study may help explain why these medications work and could inspire new nonaddictive treatments for affective pain disorders. Han also sees potential relevance for psychiatric conditions that involve heightened threat perception, such as PTSD. Quieting this pathway with CGRP blockers could offer a new approach to easing fear, avoidance, and hypervigilance in trauma-related disorders.

Importantly, the relationship between the CGRP pathway and the psychological pain associated with social experiences like grief, loneliness, and heartbreak remains unclear and requires further study.

“Our discovery of the CGRP affective pain pathway gives us a molecular and circuit-level explanation for the difference between detecting physical pain and suffering from it,” says Han. “We’re excited to continue exploring this pathway and enabling future therapies that can reduce this suffering.”

The recent study published in the Journal of Neuroscience sheds light on the brain’s decision-making process when individuals feel mentally exhausted. Researchers at Johns Hopkins University used functional MRI imaging to examine how two areas of the brain, the right insula and dorsal lateral prefrontal cortex, work together to react to and possibly regulate mental fatigue.

The experiments involved 28 healthy adult volunteers who performed memory tasks while undergoing subsequent MRI scans of their brains. The participants were given feedback on their performance and opportunities to receive increasing payments based on their performance and choices. The test results found increased activity and connectivity in both brain areas when participants reported cognitive fatigue, with activity levels more than twice the level of baseline measurements taken before starting the tests.

The study’s lead researcher, Vikram Chib, Ph.D., associate professor of biomedical engineering at Johns Hopkins University School of Medicine, notes that the findings may provide a way for physicians to better evaluate and treat people who experience overwhelming mental exhaustion, including those with depression and post-traumatic stress disorder (PTSD).

Chib and his research team found that financial incentives need to be high in order for participants to exert increased cognitive effort, suggesting that external incentives prompt such effort. The two areas of the brain may be working together to decide to avoid more cognitive effort unless there are more incentives offered.

The study’s findings have implications for understanding fatigue-related conditions and developing treatments. Chib notes that it may be possible to use medication or cognitive behavior therapy to combat cognitive fatigue, and the current study using decision tasks and functional MRI could be a framework for objectively classifying cognitive fatigue.

Overall, the study provides new insights into the brain’s decision-making process when individuals feel mentally exhausted, highlighting the importance of understanding the neural circuits involved in cognitive effort and fatigue.

A groundbreaking new study has shed light on the surprising link between hearing loss, loneliness, and lifespan. Researchers from the USC Caruso Department of Otolaryngology – Head and Neck Surgery found that adults with hearing loss who used hearing aids or cochlear implants were more socially engaged and felt less isolated compared to those who didn’t use them.

The study, published in JAMA Otolaryngology – Head & Neck Surgery, is the first to link hearing aids and cochlear implants to improved social lives among adults with hearing loss. The researchers conducted a comprehensive review of 65 previously published studies, encompassing over five thousand participants, on how hearing aids and cochlear implants affect three key measures: social quality of life, perceived social handicap, and loneliness.

The findings suggest that hearing devices can help prevent the social disconnection and broader health consequences that can follow untreated hearing loss. When left unaddressed, hearing loss can make communication difficult, leading people to withdraw from conversations and social activities. This can lead to mental stimulation reduction, increased risk of loneliness, anxiety, depression, cognitive decline, and dementia.

The researchers found that adults using hearing devices feel more socially connected and less limited in social situations. They are better able to engage in group conversations and feel more at ease in noisy or challenging listening environments. Participants also reported feeling less socially handicapped by their hearing loss, with fewer barriers and frustrations during interactions and an improved ability to stay engaged without feeling excluded.

Those with cochlear implants reported the most improvement in their social quality of life, likely because cochlear implants offer greater hearing restoration than hearing aids, especially for individuals with more severe hearing loss. As a result, they may experience more noticeable improvements in social engagement once their hearing is restored.

While it was outside the scope of the study to measure how better social lives relate to improved cognitive outcomes, the researchers believe there may be a connection. Previous research has found managing hearing loss may be key to reducing the risk of cognitive decline and dementia. The study’s lead researcher, Janet Choi, MD, MPH, an otolaryngologist with Keck Medicine, believes that by restoring clearer communication, hearing devices may help preserve cognitive health by keeping the brain more actively involved and people more connected.

This research follows a January 2024 study by Choi showing that adults with hearing loss who use hearing aids have an almost 25% lower risk of mortality, suggesting that treating hearing loss can improve lifespan as well as social quality of life. These findings add to a growing body of research showing that hearing health is deeply connected to overall well-being.