Concordance of cortical morphological anomalies with genetic predisposition to multisite chronic pain in females

April 1, 2026

Korean Journal of Pain

Authors: Aihui Liu, Shinan Li, Yu Wang, Xiuwen Wang, Shuaijie Ding, Shiyi Wu, Zhi Ye, Ruitian Ma, Yixin Zhou, Sheng Qiu, Qiang Gao, Zhenhua Ying, Hongyang Jiang

Link: https://doi.org/10.3344/kjp.25253

TLDR: This study looked at how the genetics of females with Multisite Chronic Pain (MCP) were related to changes in the thickness and surface area of the outer layer of the brain (grey matter). A relationship was found between certain genetic factors and the frontal, temporal and parietal parts of the brain in these females. Thickness of this outer layer and the total surface area of this outer layer tended to be lower. These researchers found that genetics can influence the pain that females feel and the brain structure itself. The areas in the brain that are affected frequently relate to how humans perceive and emotionally process chronic pain. Therefore, these researchers found that genetics can influence brain changes that influence how some females feel and process pain.

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Multisite chronic pain (MCP) is a clinical symptom seen in millions of people around the world, especially in females. Typically, patients experience chronic pain that persists or comes and goes in at least 3 body parts and lasts more than 3 months. These patients also frequently experience more complications, like poor mobility, difficulty sleeping and difficulty regulating emotions. Overall, this tends to result in serious negative impact on their quality of life. Research has shown many factors that support development of this syndrome, especilally in the brain and spinal cord. In these patients, chronic inflammation can cause the neurons to reorganize themselves (neuroplasticity). This is related to an increase in pain sensitivity throughout the body (central pain sensitization). As a result, pain is felt more intensely, more easily and persists longer.

MCP seems to have certain genetic attributes that make it more likely to occur in some people than others. Researchers have found this in twins and families who are more likelyto experience pain in 3 or more sites. Already, research has identified at least 113 genes associated with inheriting MCP tendencies, and this is slightly more likely to happen in females than males. Some of these changes appear to impact how the nervous system develops and the ongoing changes as these patients age.

Research has shown that patients with MCP commonly have changes in specific brain regions. There is less grey matter in the brain in regions such as the insula, anterior and posterior cingulate, thalamus, hippocampus, and basal ganglia, and the amount of surface area on the brain. This research into genes and symptoms is similar to some research on Parkinson’s and Alzheimer’s diseases.

Researchers have found females generally feel pain easier and tend to have difficulty tolerating pain when compared to males. This naturally makes females more easily to develop a more intense feeling of pain and experiencing pain as more emotional unpleasant. This may help explain why researchers tend to find females are more disabled by pain than males. This in turn may help explain the negative changes in the quality of life in females from pain and why females tend to access healthcare more frequently for pain-related reasons.

In this study, researchers looked at 51,665 people from around the world. Most (94%) were of European background or ancestors. They were able to identify 34 brain regions where there were changes to the thickness of the outer layer of the brain (cortical thickness) and surface area of the outer layer of the brain. They found changes in the frontal and parietal cortexes (front and sides of the brain) where the thickness of the grey matter was reduced.

Researchers looked at whether there were common genetic changes among certain traits. In females with MCP they looked at genetic associations 136 different ways. They found a relationship between the brain’s surface area in certain areas and the ease at which females develop MCP. They also found a relationship between the genetics and the brains outer level surface area and thickness that showed a higher risk for females to have MCP.

These researchers found specific areas of genetics were associated with MCP, and these areas tended to be related to how cells produce energy and increase oxidative stress, which can increase the likelihood of chronic pain developing. They also found changes in areas of genes that increase chances of obesity, inflammation, which both increase chronic pain.

The areas in the brain that are affected frequently relate to how humans perceive and emotionally process chronic pain. The very front of the brain processes emotions and how we cognitively think about pain; this changes how we perceived and respond when painful is triggered. A bit farther back in the front of the brain is responsible for part of how we respond emotionally and pay attention to pain and is highly related to our emotional processing systems. Another area in the front of the brain supports how we perceive stress and how much we are impacted by depressive symptoms. In addition to those areas in the front of the brain, some parts that are deeper in the brain help us to understand the sensory and emotional parts of pain. These brain changes can increase the overall ease at which we feel pain, and the difficulty in managing it.

There are studies that have shown these changes are not permanent and may be reversed. This is a critical area for researchers to start studying.

Liu A, Li S, Wang Y, Wang X, Ding S, Wu S, Ye Z, Ma R, Zhou Y, Qiu S, Gao Q, Ying Z, Jiang H. Concordance of cortical morphological anomalies with genetic predisposition to multisite chronic pain in females. Korean J Pain 2026;39:260-271. https://doi.org/10.3344/kjp.25253