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 devastating effects of spinal cord injuries have left millions without hope for recovery. However, groundbreaking research at Waipapa Taumata Rau, University of Auckland, has sparked new possibilities. Scientists have successfully used an implantable electronic device to restore movement in rats with spinal cord injuries, offering a glimmer of hope for humans and their pets.

Spinal cord injuries disrupt the communication between the brain and body, resulting in a loss of function. Unlike cuts on the skin, which typically heal on their own, the spinal cord does not regenerate effectively, making these injuries currently incurable. However, researchers have harnessed the same electrical guidance system that naturally occurs before birth to encourage nerve tissue growth along the spinal cord.

Lead researcher Dr. Bruce Harland explains, “We developed an ultra-thin implant designed to sit directly on the spinal cord, precisely positioned over the injury site in rats.” The device delivers a carefully controlled electrical current across the injury site, aiming to stimulate healing and restore lost functions.

In a 12-week study, rats that received daily electric field treatment showed improved movement and responded more quickly to gentle touch compared to those who did not. This indicates that the treatment supported recovery of both movement and sensation, with no signs of inflammation or damage to the spinal cord.

The new study, published in Nature Communications, is a result of a partnership between the University of Auckland and Chalmers University of Technology in Sweden. Long-term, the goal is to transform this technology into a medical device that could benefit people living with life-changing spinal-cord injuries.

“This study offers an exciting proof of concept showing that electric field treatment can support recovery after spinal cord injury,” says doctoral student Lukas Matter from Chalmers University. The next step is to explore how different doses and treatment regimens affect recovery, to discover the most effective recipe for spinal-cord repair.

The skin serves as our body’s first line of defense against external threats. As we age, however, the epidermis – the outermost layer of skin – gradually becomes thinner and loses its protective strength. Research has long emphasized the benefits of vitamin C (VC) in maintaining skin health and promoting antioxidant properties.

Recently, a team of researchers in Japan made an exciting discovery: VC helps thicken the skin by directly activating genes that control skin cell growth and development. Their findings, published online in the Journal of Investigative Dermatology, suggest that VC may restore skin function by reactivating genes essential for epidermal renewal.

Led by Dr. Akihito Ishigami, Vice President of the Division of Biology and Medical Sciences at Tokyo Metropolitan Institute for Geriatrics and Gerontology, the study used human epidermal equivalents – laboratory-grown models that closely mimic real human skin. In this model, skin cells are exposed to air on the surface while being nourished from underneath by a liquid nutrient medium.

The researchers applied VC at concentrations comparable to those typically transported from the bloodstream into the epidermis and found that VC-treated skin showed a thicker epidermal cell layer without significantly affecting the stratum corneum (the outer layer composed of dead cells) on day seven. By day 14, the inner layer was even thicker, and the outer layer was found to be thinner, suggesting that VC promotes the formation and division of keratinocytes.

Importantly, the study revealed that VC helps skin cells grow by reactivating genes associated with cell proliferation. This process occurs through DNA demethylation – a process in which methyl groups are removed from DNA, allowing for gene expression and promoting cell growth.

The researchers further identified over 10,138 hypomethylated differentially methylated regions in VC-treated skin and observed a 1.6- to 75.2-fold increase in the expression of 12 key proliferation-related genes. When a TET enzyme inhibitor was applied, these effects were reversed, confirming that VC functions through TET-mediated DNA demethylation.

These findings reveal how VC promotes skin renewal by triggering genetic pathways involved in growth and repair. This suggests that VC may be particularly helpful for older adults or those with damaged or thinning skin, boosting the skin’s natural capacity to regenerate and strengthen itself.

“We found that VC helps thicken the skin by encouraging keratinocyte proliferation through DNA demethylation, making it a promising treatment for thinning skin, especially in older adults,” concludes Dr. Ishigami.

This study was supported by grants from the Japan Society for the Promotion of Science (JSPS) KAKENHI: grant number 19K05902.