Neuroplasticity in chronic pain: insights into diagnosis and treatment

April 1, 2025

Korean Journal of Pain

Author: Sahar M. Jaffal

Link: https://doi.org/10.3344/kjp.24393

TLDR: Researchers have found specific changes in the brain and spinal cord that seem to be caused by chronic pain, and in turn make chronic pain worse. These areas are related to how pain feels (sensitivity, intensity, characteristics of pain), how we emotionally process while in pain and how we think when in pain. Treatments that influence the nervous system to change may be helpful in the treatment of chronic pain and even reverse some of these changes in the brain and spinal cord.

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This article is a review of recent chronic pain neuroscience, published in 2025. Chronic pain over time can change the neural networks in the nervous system. This can happen in the central nervous system (brain and spinal cord) or the peripheral nervous system (nerves that leave the central nervous system).

Chronic pain can be the result of nociceptive pain (injury to the tissues) or neuropathic pain (injury to nervous system tissue like a nerve or the spinal cord itself) which over time causes changes to the central nervous system (nociplastic pain). Often, these changes are not helpful for living life as we want to. These changes can alter how pain is felt, such as over sensitive to painful sensations, or cause the sensation of pain to non-painful stimulation.

Chronic pain can cause changes at the neuron-level, meaning the structures of the brain and spinal cord can change in tiny (but important) ways. This happens because human brains can update their own wiring, called neuroplasticity. There are certain areas in the brain where this tends to happen more when chronic pain occurs. Some of these areas of the brain help keep pain from the extremes, meaning not under sensitive or over sensitive. These can also happen in areas of the brain that control emotions related to pain.

Some areas of the brain help us discriminate sensory information related to pain. One area can record the location and severity of the painful event, or stimuli. Another area changes how intense we feel that pain and how our emotions respond to it. Together, these areas help our bodies understand some of the feelings and emotions related to pain.

Pain is complex, and is the result of a relay chain amongst many areas of the body. In one chain that involves the spinal cord, pain can be increased or decreased through the same chain. This has been studied in animals and using brain imaging techniques and can be seen when researching pain management drugs. And in turn, these chains can alter motivation, emotions and cognitive ability when related to pain.

There are also patterns within brain activity that are related to how we perceive pain. These are sometimes called “Neurological Pain Signature” (NPS). This was discovered by using special MRI machines (called fMRI) and using the same painful stimuli on multiple subjects. By doing this, they found specific brain regions that frequently became more active during acute pain. This has helped researches discover where and how pain in processed in the brain.

In one region called the ventromedial prefrontal cortex (vmPFC), they found patterns which make managing emotions and thinking clearly while in pain ore difficult. When researches watch these specific areas in the brain when a participant takes a pain medication, they can see how much of a change it makes in those pain patterns. For example, they have found that pain from osteoarthritis is often more sensitive to Naproxen.

Using these fMRI research techniques, researchers have also found significant changes in both the central (brain and spinal cord) and peripheral (nerves that extend outside of the brain and spinal cord). These areas were then mapped to certain areas in the brain that influence sensory, emotional and cognitive aspects of pain. This shows the CNS and PNS can have a lot of changes which are not beneficial to our nervous systems.

Humans have “white matter” and “grey matter” in our brain and spinal cord. With chronic pain, the grey matter can get smaller, which correlates to longer and more intense episodes of pain. Researchers have found changes in the spinal cord can lead to a state of oversensitivity.

Pain doesn’t come from grey matter changes alone. The connective cells around the neurons can impact if and how chronic pain develops. Some of the systems in the brain or spinal cord that usually help keep pain in check, but when they have reduced function pain can persist longer.

These changes in pathways in the brain and spinal corder can also change the way humans respond to pain in cognitive, emotional and self-awareness responses. These changes are seen in chronic fatigue syndrome. They can affect the working memory, decision making, and working towards our goals (big or small). The end result is chronic pain impairing cognitive function, ability to regulate our emotions and changes how we feel pain.

In addition to neurons in the central nervous system, there are cells around the neurons. Some of these cells can suggest there is inflammation around the neurons which can change how the neurons talk with each other and send signals. These inflammatory factors can increase the activity of neurons that process pain, and may eventually change the structure to generate more persistent pain.

At the DNA level, parts of DNA in the spinal cord can contribute to the central sensitization (over sensitive) and inflammation with pain. Researchers are also starting to recognize that reducing some parts can also reduce the sensitivity to pain, even normalizing the connections between circuits in the brain and spinal cord. Some of these discoveries pay eventually lead to new therapies and medications to treat chronic pain.

The grey matter in the brains of people with chronic pain has been shown to decrease in specific areas of the brain. The structures in these areas shrink with longer duration of pain. These findings suggest that changes in the brain can worsen with prolonged pain, making it more difficult for managing pain. This has been noted especially in patients with fibromyalgia, chronic back pain and migraines. These changes also show a relationship to pain intensity, ability to regulate emotions and cognitive difficulties. Knowing these changes means researchers may one day be able to evaluate the effects of pain therapies.

Interestingly, the parts of the brain that help us regulate emotions around pain can be altered by pain, so that the frequency of pain occurs more, we have difficulty controlling our emotions related to it and this further impacts our pain control. For example, studies have found that emotions like anxiety and depression can worsen the immune system through these same pathways. It’s a vicious cycle, pain changes how the nervous system works, and these changes from pain make the pain itself worse.

Various treatments have shown positive results when treating chronic pain, including positive changes in the nervous system structure and brain volume in specific areas. In particular, therapies that focus on regaining lost brain volume can see positive changes in pain management.

These findings in brain, spinal cord and nervous system changes have opened possibilities into new treatments. Some new treatments are more difficult to access, and may include technology aimed at crossing the skull to promote changes in the brain, or EEG with brain modulation strategies. Unfortunately, most of these are only available in research studies. More readily available treatments like CBT, exercise, stretching and movement programs are also available.

Jaffal SM. Neuroplasticity in chronic pain: insights into diagnosis and treatment. Korean J Pain 2025;38:89-102. https://doi.org/10.3344/kjp.24393