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 genetic factors in 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). Researchers found a relationship between certain genetic factors and changes in the frontal, temporal and parietal parts of the brain. In these areas, both the thickness and total surface area tended to be lower. This suggests that genetics may influence both the pain that females feel and the structure of the brain itself. These affected areas are involved in how humans perceive and emotionally process chronic pain. The researchers therefore found that genetics may contribute to brain changes that affect how some females feel and process pain.

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Multisite chronic pain (MCP) is experienced by millions of people around the world, especially females. Typically, people experience chronic pain that persists or comes and goes in at least 3 body parts and lasts more than 3 months. They also frequently experience other complications, such as poor mobility, difficulty sleeping and difficulty regulating emotions. Overall, this can have a serious negative impact on their quality of life.

Research has shown there are many factors that may contribute to the development of this syndrome, especially in the brain and spinal cord. Chronic inflammation can cause neurons to reorganize themselves, a process called neuroplasticity. This is related to an increase in pain sensitivity throughout the body, called central sensitization. As a result, pain may be felt more intensely, triggered more easily and last longer.

MCP seems to have certain genetic characteristics that make it more likely to occur in some people than others. Researchers have found evidence of this in studies of twins and families, where pain in 3 or more sites appears more likely to run in families. Research has already identified at least 113 genes associated with a tendency to develop MCP, and MCP is slightly more likely to occur in females than males. Some of these genetic differences appear to affect how the nervous system develops and changes as people age.

Research has shown that people with MCP commonly have changes in specific brain regions. There is less grey matter in areas such as the insula, anterior and posterior cingulate, thalamus, hippocampus and basal ganglia. Some parts of the brain also have a smaller surface area. This type of research, which looks at links between genes and symptoms, is also used in research on Parkinson’s and Alzheimer’s diseases.

Researchers have found that females generally feel pain more easily and have more difficulty tolerating pain than males. This may make females more likely to experience more intense pain and greater emotional distress related to pain. It may also help explain why females tend to experience greater disability from pain than males. This, in turn, may help explain the negative impact pain has on quality of life and why females 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 ancestry. They identified 34 brain regions with changes in the thickness or surface area of the brain’s outer layer. They found changes in the frontal and parietal cortices—the front and sides of the brain—where the grey matter was thinner.

Researchers also looked for genetic changes that were shared across different traits. In females with MCP, they examined genetic associations in 136 different analyses. They found a relationship between the surface area of certain brain regions and how likely females were to develop MCP. They also found a relationship between genetic factors and the surface area and thickness of the brain’s outer layer. Together, these relationships were associated with a higher risk of MCP in females.

The researchers found specific genetic regions associated with MCP. These regions tended to be related to how cells produce energy and to oxidative stress, which may increase the likelihood of chronic pain developing. They also found changes in genes associated with obesity and inflammation, both of which can increase chronic pain.

The affected brain regions are often involved in how humans perceive and emotionally process chronic pain. The very front of the brain processes emotions and how we think about pain. Changes in this area can affect how we perceive and respond when pain is triggered. An area slightly farther back helps control how we respond emotionally and pay attention to pain. It is closely connected to our emotional processing systems.

Another area in the front of the brain affects how we perceive stress and how strongly depressive symptoms affect us. Deeper parts of the brain help process the sensory and emotional aspects of pain. Together, these brain changes can make pain easier to feel and harder to manage.

Some studies have shown that these changes may not be permanent and may be reversed. This is an important area for further research.

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