If you’ve been diagnosed with Complex Regional Pain Syndrome, you may have noticed something alarming: the pain that started in your injured hand is now affecting your entire arm, or worse, it’s begun appearing in your opposite limb. This spreading pattern is one of the most confusing and frightening aspects of CRPS. The answer lies in fundamental changes happening within your nervous system—both at the injury site and in your brain and spinal cord. Understanding these changes can help you make sense of what’s happening in your body and why early, specialized treatment matters.
The Central Nervous System Connection
For years, researchers believed CRPS was primarily a problem at the injury site. We now know that’s only part of the story. CRPS is fundamentally a central nervous system condition, meaning the brain and spinal cord undergo significant changes that amplify and spread pain signals (Jänig & Baron, 2003).
When you experience an injury—even a minor one like a sprained ankle or a fracture—your nervous system launches a normal inflammatory response. In most people, this response calms down as healing progresses. But in CRPS, something goes wrong with the shutoff switch. The inflammatory signals continue long after the original tissue has healed, and these persistent signals begin rewiring your nervous system.
Dr. Harrison Irons, founder of Southern Ketamine & Wellness in Birmingham and Auburn, Alabama, has treated numerous CRPS patients throughout his career as a double board-certified anesthesiologist and pain management physician. Having worked in the surgical ICU and operating room at the VA hospital, Dr. Irons witnessed firsthand how CRPS can develop after seemingly routine procedures. “What makes CRPS so challenging is that the pain becomes independent of the original injury,” he explains. “We’re dealing with changes in how the brain processes pain signals.”
Three Pathways That Drive CRPS Progression
Recent research has identified three primary mechanisms that explain why CRPS spreads beyond the original injury site (Ferraro et al., 2024):
1. Inflammatory Mechanisms and Neuroinflammation
When CRPS develops, your immune system doesn’t just respond at the injury site—it creates widespread inflammation throughout your nervous system. This process, called neuroinflammation, involves both your peripheral nerves and your central nervous system (Zhang et al., 2023).
Inflammatory cells infiltrate nerve tissue and release chemical messengers called cytokines. These cytokines sensitize pain receptors, making them fire more easily and more intensely. This is why something as gentle as a bedsheet touching your skin can cause severe pain—your nervous system has become hypersensitive to normal stimuli.
What’s particularly problematic is that this neuroinflammation creates a feedback loop. Pain signals traveling to your spinal cord and brain trigger more inflammation, which creates more pain signals. This cycle helps explain why CRPS can persist for months or years after the original injury has healed.
2. Vasomotor Dysfunction
You may have noticed that your affected limb changes color—sometimes it’s red and hot, other times it’s pale and cold. These aren’t just cosmetic changes; they reflect profound dysfunction in how your nervous system controls blood flow.
CRPS disrupts the autonomic nervous system, which automatically regulates functions like blood vessel dilation and constriction. In early CRPS, blood vessels often dilate excessively, causing warmth and redness. As the condition progresses, vasoconstriction may dominate, leading to coldness and color changes (Ferraro et al., 2024).
These blood flow problems aren’t limited to the originally injured area. The autonomic dysfunction can spread, affecting circulation patterns throughout the limb and even involving the opposite side of the body.
3. Maladaptive Neuroplasticity
Perhaps the most significant discovery in CRPS research is understanding how the brain itself changes. Your brain contains a “map” of your body, with specific regions dedicated to processing sensations from each body part. In CRPS, these brain maps become distorted.
Brain imaging studies show that the area representing the affected limb may shrink or become disorganized. Meanwhile, pain-processing regions become hyperactive. These changes represent maladaptive neuroplasticity—your brain is reorganizing itself, but in ways that amplify rather than reduce pain (Jänig & Baron, 2003).
This brain reorganization helps explain several puzzling CRPS symptoms:
- Why pain can spread beyond the original injury site to involve the entire limb
- Why symptoms sometimes “mirror” to the opposite limb
- Why some patients report feeling disconnected from their affected limb
- Why pain persists even after the original tissue has completely healed
Why CRPS Can Affect the Opposite Limb
One of the most distressing developments for CRPS patients is when pain and symptoms appear in the limb opposite to the original injury. This happens in approximately 10-15% of cases and reflects the centralization of the condition.
When one limb develops CRPS, the brain changes aren’t confined to just the neurons processing that specific limb. The widespread neuroinflammation and altered pain processing can affect how the entire nervous system functions. Additionally, you may unconsciously change how you move and use your body to protect the painful limb, which can stress the opposite side and potentially trigger CRPS there as well.
The Importance of Understanding These Mechanisms
You might wonder why it matters to understand these complex biological processes. There are several important reasons:
Treatment timing becomes critical. The longer CRPS persists, the more entrenched these nervous system changes become. Research consistently shows that outcomes improve when treatment begins within the first year of symptom onset (Ferraro et al., 2024). This is because it’s easier to prevent maladaptive brain changes than to reverse them once they’re established.
It explains treatment approaches. Effective CRPS treatment must address the central nervous system changes, not just symptoms at the injury site. This is why Southern Ketamine & Wellness utilizes ketamine infusion therapy—ketamine works directly on NMDA receptors in the brain and spinal cord to help “reset” the amplified pain processing that drives CRPS.
It validates your experience. Many CRPS patients have been told their pain is “out of proportion” to their injury or even that it’s psychological. Understanding that CRPS involves measurable, physical changes in your nervous system can provide validation that what you’re experiencing is real and has a biological basis.
What You Can Do This Week
While CRPS requires professional treatment, understanding these mechanisms empowers you to take active steps:
- Document your symptoms carefully. Keep a journal noting when pain spreads to new areas, changes in skin color or temperature, and any movement difficulties. This information helps healthcare providers understand your CRPS progression and adjust treatment accordingly.
- Avoid immobilization. Although movement may be painful, research shows that gentle, guided movement helps prevent the spread of CRPS symptoms. Work with a physical therapist familiar with CRPS to develop a safe movement plan. Immobilization can actually worsen the brain reorganization that drives symptom spread.
- Seek evaluation from a specialist experienced in CRPS treatment. In Alabama, specialized treatment options exist that target the central nervous system changes underlying CRPS. The sooner you connect with experienced providers, the better your chances of limiting symptom progression.
Finding Appropriate Care in Alabama
For Birmingham and Auburn area residents dealing with CRPS, access to specialized treatment is improving. Southern Ketamine & Wellness offers consultation for patients whose CRPS has not responded to standard treatments. Dr. Irons’ background in both anesthesiology and pain management provides comprehensive understanding of both the mental and physical pain components of CRPS.
Treatment approaches vary based on individual presentation, and results differ from person to person. What works well for one patient may need adjustment for another. The goal is always to work in conjunction with your existing healthcare team to provide relief and improve function.
To learn is to understand, and to understand is to heal. Learning about the nervous system changes driving your CRPS symptoms is the first step toward finding effective treatment and reclaiming your quality of life.
References
Ferraro, M.C., O’Connell, N.E., Sommer, C., Goebel, A., Schlereth, T., Bultitude, J.H., … & Birklein, F. (2024). Complex regional pain syndrome: advances in epidemiology, pathophysiology, diagnosis, and treatment. The Lancet Neurology, 23(5), 522-533. https://www.sciencedirect.com/science/article/abs/pii/S1474442224000760
Jänig, W., & Baron, R. (2003). Complex regional pain syndrome is a disease of the central nervous system. Clinical Autonomic Research, 13(2), 79-88. https://pubmed.ncbi.nlm.nih.gov/12269546/
Zhang, Y., Liu, Y., Liu, D., Zhang, H., Xie, X., Yang, Y., … & Ye, L. (2023). The Role of Neuroinflammation in Complex Regional Pain Syndrome: A Comprehensive Review. Frontiers in Immunology, 14. https://pubmed.ncbi.nlm.nih.gov/37701560/
