Neuroplasticity in chronic pain: insights into diagnosis and treatment
Updated: 5 days ago
April 1, 2025
Korean Journal of Pain
Author: Sahar M. Jaffal
TLDR: Researchers have identified changes in the brain, spinal cord and peripheral nervous system that are associated with chronic pain and may, in turn, help maintain or worsen it. The affected areas are involved in how pain feels—including its sensitivity, intensity and characteristics—as well as how we process emotions and think while in pain. Treatments that support helpful changes in the nervous system may improve chronic pain and, in some studies, have been associated with partial reversal of some nervous-system changes.
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This article is a review of recent chronic pain neuroscience, published in 2025. Over time, chronic pain is associated with changes in neural networks throughout the nervous system. These changes can occur in the central nervous system—the brain and spinal cord—and in the peripheral nervous system, which includes the nerves extending outside the brain and spinal cord.
Chronic pain can involve nociceptive pain, related to actual or threatened injury to non-neural tissue; neuropathic pain, related to a lesion or disease of the nervous system; or nociplastic pain, in which pain processing is altered even when the pain is not fully explained by tissue damage or a lesion of the somatosensory system. More than one type of pain mechanism can be present at the same time. Changes in the nervous system can alter how pain is experienced, making a person more sensitive to painful sensations or causing pain in response to stimulation that would not normally be painful.
Chronic pain is also associated with changes at the level of individual neurons and in the structure and function of parts of the brain and spinal cord. This is possible because the nervous system can change and adapt—a process called neuroplasticity. Some of the areas commonly affected help regulate pain sensitivity. Others are involved in attention, thinking and emotional responses to pain.
Some brain regions help us distinguish between different types of sensory information related to pain. One area may help identify the location and intensity of a painful event or stimulus. Another affects how intensely we experience pain and how we respond emotionally to it. Together, these areas contribute to the sensory and emotional experience of pain.
Pain is complex and involves networks of signals travelling through many parts of the nervous system. Some pathways involving the spinal cord can either increase or decrease pain. Researchers have studied these pathways in animals, through brain imaging and while testing pain medications. These same networks can also interact with motivation, emotions and thinking when a person is in pain.
Researchers have identified patterns of brain activity associated with how people perceive pain. One of these is called the Neurologic Pain Signature, or NPS. It was identified using a special type of MRI called functional MRI, or fMRI, while applying similar painful stimuli to multiple participants. Researchers found a pattern of brain regions that frequently became more active during acute pain. This has helped them investigate how pain is processed in the brain, although brain imaging is not currently a stand-alone diagnostic test for an individual person’s pain.
In a region called the ventromedial prefrontal cortex, or vmPFC, researchers have found changes related to emotion, thinking and pain. Researchers can also examine whether activity in pain-related brain networks changes after a participant receives pain medication. For example, studies discussed in the review found brain-imaging changes associated with the response of osteoarthritis pain to naproxen.
Using fMRI and other research methods, researchers have found functional and structural differences involving both the central and peripheral nervous systems in people with chronic pain. Many of the affected regions contribute to the sensory, emotional and cognitive aspects of pain. These findings show that chronic pain can involve widespread nervous-system changes that may affect how pain is experienced and managed.
Humans have white matter and grey matter in the brain and spinal cord. Some studies have found lower grey-matter volume in particular brain regions in people with chronic pain. These differences have been associated with longer-lasting or more intense pain. Researchers have also identified spinal-cord changes associated with increased sensitivity. These findings describe relationships between pain and nervous-system changes; they do not mean that grey-matter differences alone cause a person’s pain.
Pain does not arise from grey-matter changes alone. Glial cells—the cells surrounding and supporting neurons—can also influence whether and how chronic pain develops. In addition, some systems in the brain and spinal cord normally help control or reduce pain. Pain may persist when these pain-inhibiting systems are not functioning effectively.
Changes in brain and spinal-cord pathways may also affect cognitive, emotional and self-awareness responses to pain. Related changes have been observed in conditions such as chronic fatigue syndrome. They may affect working memory, decision-making and the ability to work toward goals. As a result, chronic pain can interfere with thinking and emotional regulation while also changing how pain is experienced.
Glial cells may also contribute to inflammation around neurons, changing how neurons communicate and send signals. Inflammatory processes can increase the activity of neurons involved in pain and may contribute to longer-lasting changes in the nervous system.
At the level of gene activity, changes in the spinal cord may contribute to central sensitization and pain-related inflammation. Early research suggests that altering some of this activity could reduce pain sensitivity and affect connections between circuits in the brain and spinal cord. This research may eventually contribute to new therapies and medications for chronic pain, although much of it remains experimental.
Studies have found lower grey-matter volume in particular brain regions in people with conditions such as fibromyalgia, chronic back pain and migraine. These differences have been associated with pain duration or intensity, emotional regulation and cognitive difficulties. Researchers are continuing to study whether these changes contribute to persistent pain, result from it, or reflect a combination of both.
The parts of the brain that help regulate emotions around pain may themselves be affected when pain persists. As pain becomes more frequent, it may become harder to manage the thoughts and emotions connected with it, which can further affect the pain experience. Anxiety, depression, immune activity and pain can also influence one another through overlapping biological and psychological pathways. This can create a cycle in which pain affects the nervous system and those changes may then help maintain the pain.
Various chronic-pain treatments have been associated with improvements in symptoms and with changes in nervous-system function or structure. In some studies, changes in brain volume have moved toward patterns seen in people without chronic pain as pain and function improved. This does not mean that treatment simply “regrows” the brain, but it does provide evidence that at least some pain-related nervous-system changes may not be permanent.
These findings have opened possibilities for new treatments. Some emerging approaches use technologies that act through the skull to influence brain activity or use EEG-based feedback and brain-modulation strategies. Many remain available mainly through research studies. More accessible treatments discussed in the review include cognitive behavioural therapy, exercise, stretching and movement-based programs.
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
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