Why Chronic Pain is Often a Brain Condition - Not a Tissue Problem

Chronic Pain Is Often a Brain Condition, Not Just a Physical Injury

Chronic pain—defined as pain lasting longer than three months—affects over 20% of adults worldwide and remains one of the most misunderstood medical conditions. While acute pain usually reflects tissue injury or inflammation, chronic pain often persists even after the original injury has healed. Modern neuroscience now recognizes that chronic pain is often a brain condition, not caused by ongoing tissue damage, but by alterations in how the brain and spinal cord process pain signals (Nijs et al., 2021).

This shift in understanding reframes chronic pain as a central nervous system disorder, sometimes referred to as nociplastic pain, in which the nervous system itself becomes hypersensitive and continues to produce pain in the absence of clear peripheral damage (IASP, 2021).

How This Happens

Central Sensitization

One of the best-supported mechanisms underlying chronic pain is central sensitization—a state in which neurons in the brain and spinal cord become hyperresponsive to sensory input. Over time, repeated pain signaling lowers the nervous system’s threshold for danger, such that even mild or non-painful stimuli can elicit significant pain (Woolf, 2021).

Instead of pain reflecting injury severity, it begins to reflect neural amplification.

Neuroplastic Changes in the Brain

Functional neuroimaging studies show that chronic pain is associated with measurable changes in brain structure and connectivity. Regions involved in pain perception, emotional regulation, and threat detection—such as the insula, anterior cingulate cortex, and prefrontal cortex—demonstrate altered activity patterns in people with persistent pain (Kuner & Flor, 2017; Martucci & Mackey, 2021).

These changes do not mean pain is imagined. They suggest that the brain has learned to perceive pain as a protective strategy.

Neuroinflammation and Stress Hormones

Chronic stress, trauma, and prolonged illness can activate neuroimmune responses. Elevated inflammatory mediators and dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis further sensitize pain pathways, reinforcing the pain-stress loop (McEwen & Akil, 2020; Burke et al., 2021).

How Can This Be Diagnosed?

Unlike fractures or arthritis, chronic pain driven by central mechanisms does not appear clearly on imaging studies.

Diagnosis relies on:

• Clinical history (pain persisting beyond tissue healing)

• Pain disproportionate to exam or imaging findings

• Widespread, fluctuating, or stimulus-sensitive pain

Validated tools may include:

• Central Sensitization Inventory (CSI) — identifies symptom clusters associated with nervous system sensitization (Nijs et al., 2021)

• Quantitative Sensory Testing (QST) — assesses abnormal sensory processing patterns (Backonja et al., 2021)

Importantly, the absence of structural findings does not invalidate pain. It indicates a different biological driver.

What Makes Chronic Pain Better or Worse

Factors That Worsen Pain

• Psychological stress and emotional threat

• Poor sleep quality

• Repeated fear-based avoidance of movement

• Ongoing uncertainty or invalidation

These factors heighten nervous system arousal and reinforce pain signaling (Finan et al., 2021).

Factors That Improve Pain

• Pain neuroscience education

• Graded, consistent movement

• Stress-regulation strategies

• Trauma-informed care

  
  

Treatments that address nervous system regulation—rather than targeting only tissues—yield better long-term outcomes for many patients with chronic pain (Moseley et al., 2022).

Clinical Scenario

A patient sustains a lower-back injury that resolves structurally within months. Imaging shows no ongoing damage, yet pain persists and spreads. Sitting, stress, or even a light touch provoke discomfort.

This presentation reflects central nervous system sensitization rather than ongoing injury. The brain continues to interpret sensory input as dangerous, maintaining pain as a learned protective response (Nijs et al., 2021).

Conclusion

Chronic pain is not a failure of healing—it is often a misfiring of protection. Advances in neuroscience demonstrate that persistent pain frequently reflects changes in the brain and spinal cord rather than unresolved tissue damage.

Recognizing chronic pain as a nervous system condition:

• Validates patient experiences

• Explains why scans may appear normal

• Shifts treatment toward regulation, education, and neural retraining

Pain is real—whether its origin is tissue, nerve, or brain. Understanding this distinction is essential for compassionate, effective care.

References

Backonja, M. M., Attal, N., Baron, R., Bouhassira, D., Drangsholt, M., Dyck, P. J., … Wallace, M. S. (2021). Value of quantitative sensory testing in neurological and pain disorders. Neurology, 97(2), 61–71. https://doi.org/10.1212/WNL.0000000000012194

Burke, N. N., Finn, D. P., McGuire, B. E., & Roche, M. (2021). Psychological stress in chronic pain: Implications for neuroimmune modulation. Brain, Behavior, and Immunity, 87, 16–30. https://doi.org/10.1016/j.bbi.2020.11.001

Finan, P. H., Goodin, B. R., & Smith, M. T. (2021). The association of sleep and pain: An update and a path forward. Journal of Pain, 22(1), 1–14. https://doi.org/10.1016/j.jpain.2020.08.007

IASP. (2021). IASP terminology and pain definitions. International Association for the Study of Pain.

Martucci, K. T., & Mackey, S. C. (2021). Neuroimaging of pain: Human evidence and clinical relevance. Neuroscience, 338, 2–20. https://doi.org/10.1016/j.neuroscience.2016.07.009

McEwen, B. S., & Akil, H. (2020). Revisiting the stress concept: Implications for affective disorders. Journal of Neuroscience, 40(1), 12–21. https://doi.org/10.1523/JNEUROSCI.0733-19.2019

Moseley, G. L., Stanton, T. R., & Vlaeyen, J. W. S. (2022). The neuroscience of pain education. Clinical Journal of Pain, 38(3), 147–155. https://doi.org/10.1097/AJP.0000000000001000

Nijs, J., Lahousse, A., Kapreli, E., Bilika, P., Saraçoğlu, I., Malfliet, A., Coppieters, I., & Meeus, M. (2021). Nociplastic pain criteria or recognition of central sensitization? Pain Reports, 6(1), e912. https://doi.org/10.1097/PR9.0000000000000912

Woolf, C. J. (2021). Central sensitization: Implications for the diagnosis and treatment of pain. Pain, 162(S1), S2–S15. https://doi.org/10.1097/j.pain.0000000000002099