CRPS II: When Injury Triggers a Body-Wide Storm of Pain, Inflammation, and Neurovascular Chaos

 THE FIRE IN THE NERVES:
Why CRPS II Is Not Just Pain—and How Modern Diagnostics Are Rewriting Outcomes

By: Lennard Goetze, Ed.D, Carolina DeSouza, Ph.D, Joraine Viray, DO, Robert Bard, MD and Phil Koekstra, Ph.D

Introduction – When Pain Becomes a Disease
There is ordinary pain—the kind that fades as tissues heal. And then there is pain that refuses to let go. Pain that lingers, intensifies, spreads, and begins to rewrite the body’s internal signals. Complex Regional Pain Syndrome Type II (CRPS II), historically called causalgia, belongs to this second category. It is not simply a lingering injury—it is a neurovascular disorder in which trauma to a specific nerve ignites a cascade of inflammation, immune activation, vascular dysregulation, and central nervous system sensitization. For patients, CRPS II can feel like fire running through the limb: burning, stabbing, electric sensations paired with swelling, color changes, temperature shifts, and loss of function. For clinicians, it represents one of the most complex intersections of neurology, immunology, vascular physiology, and pain medicine.

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What Is CRPS II—and How Is It Different from CRPS I?

CRPS is divided into two types:

·        CRPS I: Occurs without a confirmed nerve injury

·        CRPS II (Causalgia): Follows a documented injury to a specific peripheral nerve

In CRPS II, nerve trauma—whether from surgery, fracture, crush injury, injection, or penetrating trauma—sets off an abnormal healing response. The nervous system remains locked in a hyper-alert state. Blood vessels lose normal tone regulation. Immune mediators remain elevated. The brain begins to amplify pain signals long after the initial injury has healed.

CRPS II is therefore not just “nerve pain.” It is a systems-level disorder involving:

·        Peripheral nerves

·        Microvasculature and blood flow

·        Inflammatory cytokines

·        Autonomic nervous system dysfunction

·        Central nervous system pain processing

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How Do You Get CRPS II?

CRPS II rarely appears spontaneously. It is most often the consequence of a specific moment when the integrity of a peripheral nerve is disrupted and the body’s repair response becomes dysregulated. What makes CRPS II clinically challenging is that the severity of the initiating event does not reliably predict the severity of the disease that follows. In some patients, a major traumatic injury clearly precedes the onset. In others, CRPS II develops after procedures or exposures that would normally be expected to heal uneventfully. This unpredictability reflects individual differences in neuroinflammatory sensitivity, vascular reactivity, and immune signaling.

Equally important is the fact that many initiating events are not initially recognized as “nerve injuries” at all. Subtle trauma to small peripheral nerves, procedural irritation, or transient ischemic stress to nerve tissue may not produce immediate neurological deficits, yet can still trigger a prolonged pathological response. In clinical practice, this leads to delayed recognition of the causal link between the original insult and the emerging CRPS II symptoms.

For patients, this can feel bewildering—how a seemingly routine injury or medical intervention could ignite a complex neurovascular condition. The following categories highlight the range of known initiating events, from common orthopedic and surgical scenarios to less obvious or overlooked sources of nerve trauma that clinicians are increasingly learning to recognize.

CRPS II typically follows a clear nerve insult, including:

Common triggers:

·        Orthopedic trauma (fractures, dislocations)

·        Surgical nerve injury

·        Crush injuries

·        Deep lacerations

·        Nerve compression syndromes

·        Iatrogenic injury (catheter placement, injections)

Uncommon or overlooked triggers:

·        Dental or facial nerve injury

·        Post-viral neuropathy

·        Peripheral nerve biopsy

·        Vascular access trauma

·        Military or industrial injuries

·        Rarely, post-radiation nerve damage

Notably, CRPS II can arise even after “routine” procedures. The severity of the original injury does not predict the severity of CRPS. Minor trauma can trigger catastrophic neuroinflammatory responses in susceptible individuals.

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Why Does CRPS II Happen?

CRPS II does not arise from a single malfunctioning pathway—it emerges when multiple protective systems that normally coordinate healing become locked in a state of overdrive. After nerve injury, the body initiates a complex repair response involving immune signaling, vascular regulation, and neural recalibration. In most injuries, this response resolves as tissues recover. In CRPS II, however, the “off switch” fails. The result is a self-sustaining loop in which inflammation, impaired blood flow, and heightened neural signaling continuously reinforce one another.

This maladaptive healing response alters how the affected limb is supplied with oxygen and nutrients, how nerves transmit sensory information, and how the brain interprets those signals. Over time, these disruptions extend beyond the original injury site, influencing regional circulation, tissue metabolism, and motor control. The condition becomes less about the original trauma and more about a system-wide failure of regulation between nerves, vessels, and immune mediators.

Understanding CRPS II through this systems lens is essential for effective care. It reframes the condition away from being perceived as a subjective pain disorder and toward recognition as a biologically driven neurovascular disease—one that can be observed, monitored, and therapeutically guided through objective clinical and imaging-based assessment.

 

CRPS II occurs when the body’s repair systems fail to shut off. Several mechanisms converge:

1.     Neuroinflammation – Injured nerves release inflammatory mediators that persist

2.     Microvascular dysfunction – Blood vessels lose normal constriction/dilation control

3.     Autonomic dysregulation – Abnormal sweating, temperature asymmetry, color changes

4.     Central sensitization – The brain amplifies pain signals

5.     Immune activation – Elevated cytokines maintain tissue inflammation

6.     Ischemia-reperfusion injury – Poor blood flow causes metabolic stress in tissues

CRPS II is therefore not “in the patient’s head.” It is a measurable neurovascular disease with visible tissue changes.

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Who Gets CRPS II More Often? Is There Data?

Understanding who is most affected by CRPS II has been challenging, not because patterns do not exist, but because the condition is frequently misdiagnosed, inconsistently coded, and unevenly tracked across healthcare systems. Much of what is known comes from a convergence of hospital registries, post-surgical outcome studies, pain clinic cohorts, trauma databases, military injury records, and longitudinal follow-ups in neurology and rehabilitation settings. These datasets tend to capture patients who have already entered specialty care, meaning mild or early-stage cases are often missed—contributing to underestimation of true prevalence.

Epidemiologic insights are therefore built from patterns observed after fractures, nerve injuries, and surgical interventions, rather than from population-wide screening. This makes CRPS II particularly difficult to quantify, as its diagnosis requires confirmed nerve trauma and careful clinical correlation over time. As awareness improves and diagnostic criteria become more standardized, incidence reporting continues to evolve.

Importantly, demographic patterns should be interpreted as trends rather than rigid rules. Risk appears to reflect a complex interaction between biological vulnerability, injury type, immune reactivity, and access to early intervention. The following patterns summarize what current clinical and population-level data suggest—while also underscoring how much remains to be clarified as surveillance methods improve.

CRPS overall is considered rare, but likely underdiagnosed. Epidemiologic patterns show:

·        Women are affected more often than men (approximately 2–4:1 ratio)

·        Most common onset: ages 40–60, though it occurs in children and older adults

·        Higher risk following fractures and surgery

·        Occurs across all ethnicities and nationalities

·        No strong racial predisposition has been established

·        Psychological stress does not cause CRPS, but chronic stress may worsen severity

·        Genetic susceptibility is suspected but not yet clearly defined

CRPS II is less common than CRPS I, accounting for a smaller percentage of cases because it requires confirmed nerve injury.

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How Is CRPS II Linked to the Rest of the Body?

CRPS II is not isolated to the injured limb. It is increasingly understood as a neurovascular and immune disorder with systemic effects:

 

Associated or overlapping conditions may include:

·        Diabetes (neuropathy increases susceptibility)

·        Autoimmune disorders

·        Vascular insufficiency

·        Chronic inflammatory states

·        Post-infectious syndromes

·        Central sensitization syndromes (fibromyalgia-like patterns)

CRPS II does not cause cancer, but nerve injury from cancer treatment (surgery, radiation, chemotherapy-induced neuropathy) can trigger CRPS II in vulnerable patients. Likewise, diabetic neuropathy may predispose individuals to exaggerated neuroinflammatory responses after injury.

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What Are the Worst-Case Scenarios?

CRPS II is not inherently a degenerative disease, but when it is missed, minimized, or undertreated, the biological processes driving it can progressively reshape both tissue and function. What begins as localized nerve injury and vascular instability can evolve into sustained inflammation, impaired circulation, and disordered motor signaling. Over time, these changes alter how muscles receive instruction, how joints maintain mobility, how bones sustain mineral density, and how skin and connective tissues receive nutrients and oxygen. The longer this cascade continues unchecked, the more the affected limb becomes biologically and neurologically “miswired,” making reversal increasingly difficult.

Importantly, these outcomes are not inevitable. They represent the far end of a spectrum—most often seen when diagnosis is delayed, movement is avoided due to pain, or care remains fragmented. The goal of outlining potential severe outcomes is not to alarm patients, but to underscore the urgency of early recognition and coordinated care. When CRPS II is identified early and managed with active rehabilitation, vascular support, neuroinflammatory modulation, and careful monitoring, the trajectory can be altered. The following complications reflect what can emerge when the condition is allowed to progress without timely intervention—and why early detection dramatically improves outcomes.

In severe or untreated CRPS II, progression may include:

·        Severe muscle atrophy

·        Joint contractures

·        Bone demineralization

·        Chronic edema and trophic skin changes

·        Loss of limb function

·        Spread to other limbs

·        Long-term disability

·        Severe psychological burden secondary to chronic pain

·        Rare cases of functional limb loss

 

Early detection dramatically improves outcomes.

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Treatment and Management: Can CRPS II Be Helped?

There is no single cure for CRPS II, but early, coordinated, and multimodal intervention can dramatically alter its trajectory. The opportunity to reverse or stabilize disease progression is often greatest within the first weeks to months following nerve injury, before neuroinflammation, microvascular dysfunction, and central sensitization become biologically entrenched. When treatment is delayed, pain pathways become reinforced at both peripheral and central levels, circulation patterns remain dysregulated, and motor avoidance accelerates functional decline. Effective care therefore depends on rapid recognition, interdisciplinary coordination, and continuous reassessment of tissue response.

Core strategies include early physical and occupational therapy to preserve movement and prevent contracture, combined with targeted neuropathic pain modulation and anti-inflammatory protocols to quiet ongoing nerve irritation. Sympathetic nerve blocks may help interrupt maladaptive autonomic signaling and improve regional blood flow in selected patients. In refractory cases, neuromodulation approaches such as spinal cord stimulation may offer functional pain reduction by altering aberrant signal transmission at the central level. Mirror therapy and graded motor imagery support cortical re-mapping, helping the brain re-establish non-painful motor representations. Psychological support is included not because pain is psychological, but because prolonged pain reshapes neural networks and coping systems.

Adjunctive, non-invasive technologies are also being explored as supportive tools within a comprehensive care model. Pulsed Electromagnetic Field (PEMF) therapy is under investigation for its potential effects on microcirculation, inflammation modulation, and tissue repair signaling, while neurofeedback may assist selected patients in regulating maladaptive cortical pain amplification patterns. These modalities are best positioned as complementary supports rather than stand-alone treatments, and their use should be guided by clinical monitoring and patient response.

Across all approaches, treatment is most effective when guided by objective monitoring of vascular patterns, inflammatory activity, and nerve integrity—allowing care teams to move beyond symptom suppression toward image-guided, response-driven management.

Core strategies include:

·        Early physical and occupational therapy

·        Neuropathic pain modulation

·        Sympathetic nerve blocks

·        Anti-inflammatory protocols

·        Neuromodulation (spinal cord stimulation in refractory cases)

·        Mirror therapy and graded motor imagery

·        Psychological support (not because pain is psychological—but because chronic pain reshapes the brain)

Treatment is most effective when guided by objective monitoring of tissue and vascular changes.

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The Role of Diagnostic Imaging in CRPS II

CRPS II is increasingly viewed as an image-guidable disease. Modern imaging provides objective markers of progression and response to therapy:

 

Thermal Imaging (Infrared Thermography)

·        Detects asymmetrical temperature patterns

·        Identifies neurovascular dysregulation

·        Tracks inflammatory shifts during recovery

·        Non-invasive monitoring tool

 

Doppler Ultrasound

·        Assesses blood flow abnormalities

·        Identifies microvascular compromise

·        Monitors reperfusion patterns

 

High-Resolution Ultrasound (Peripheral Nerves)

·        Visualizes nerve thickening, entrapment, or structural changes

·        Monitors nerve recovery

·        Identifies secondary nerve compression from edema

 

Fluorescence Imaging (Inflammatory Mapping)

·        Highlights superficial inflammatory activity

·        Tracks tissue perfusion and vascular response

 

Sentinel Organ Scanning

·        Emerging concept: assessing systemic vascular stress in eyes, skin, or extremities

·        Provides insight into whether CRPS reflects broader neurovascular dysregulation

Imaging transforms CRPS II from a “symptom-based diagnosis” into a measurable disease process, supporting earlier intervention and objective treatment tracking.

Conclusion – Seeing the Fire Before It Burns the System

CRPS II is not rare pain. It is a disorder of broken signaling—where injured nerves ignite inflammation, vascular instability, and neurological amplification across the body. Left unseen, it becomes disabling. Seen early, it becomes treatable. Modern diagnostic imaging now gives clinicians the ability to see the fire in the nerves before it consumes the limb—to track vascular chaos, inflammatory patterns, and nerve compromise in real time. CRPS II demands a shift from symptom management to image-guided care. The earlier we see the storm forming, the more likely we are to calm it—before pain becomes the disease.

 

 

PART II – IPHA NEWS: Diagnostic Insider

ADVANCING THE STUDIES & THE BIOLOGY OF PAIN

CRPS: From “Rare Disorder” to Measurable Neurovascular Disease (2019–2025)

Dr. Robert Bard approaches chronic pain disorders not as abstract symptom clusters, but as measurable biological processes unfolding within nerves, vessels, and tissues. In the past, conditions like Complex Regional Pain Syndrome (CRPS) were described primarily through patient-reported pain scales and clinical observation, often dismissed as rare anomalies. However, between 2019 and 2025, advances in neuroimaging, microvascular assessment, and inflammatory biomarker research have reframed CRPS as a neurovascular-inflammatory disorder with identifiable physiological signatures. What was once categorized as “rare” is increasingly recognized as underdiagnosed, particularly in post-surgical, post-fracture, and neuropathic injury populations.

Recent population-based analyses (2020–2024) continue to report CRPS incidence in the range of 5.5 to 26.2 per 100,000 person-years, with higher prevalence observed in trauma centers and rehabilitation populations. CRPS remains coded under ICD-10 classifications for Type I and Type II, yet Dr. Bard emphasizes that coding alone obscures biological nuance. The modern challenge is not classification, but detection—identifying which injured patients are entering a maladaptive neuroinflammatory loop before irreversible tissue and neural changes take hold.

CRPS as a Disorder of Measurable Dysfunction

Research from 2021–2024 increasingly supports CRPS as a disorder involving:

·        Small fiber nerve injury

·        Persistent neuroinflammation

·        Microvascular instability

·        Autonomic dysregulation

·        Central nervous system amplification

What distinguishes CRPS from routine post-injury pain is not the presence of pain itself, but the disproportionate biological response to injury. Imaging and physiological studies during this period have shown that early CRPS often presents with “warm” inflammatory hyperperfusion patterns, while chronic CRPS frequently transitions to “cold” ischemic-vasoconstrictive states—both of which are measurable through vascular and thermal assessment. These patterns correlate with disease phase and treatment responsiveness, reinforcing the need for stage-specific intervention.

Imaging Pain: Seeing What the Patient Feels

Dr. Bard’s work centers on translating invisible pain into visible physiology. Modern non-invasive imaging has become central to this shift:

High-Resolution Ultrasound (2019–2025)
Advanced ultrasound enables visualization of peripheral nerve thickening, fascial inflammation, edema-related nerve compression, and secondary vascular compromise. In CRPS II patients with known nerve injury, ultrasound can document evolving structural changes over time, providing objective markers for disease progression or stabilization.

Doppler Vascular Imaging (2020–2025)
Microvascular flow abnormalities are a hallmark of CRPS. Doppler studies allow clinicians to measure perfusion asymmetry, venous congestion, and arterial tone dysregulation—findings that correlate with “warm” versus “cold” CRPS phenotypes described in recent literature (2022–2024). These perfusion signatures also inform the timing of vascular-targeted interventions and rehabilitation intensity.

Infrared Thermal Imaging (Thermography) (2021–2025)
Thermal asymmetry between affected and contralateral limbs reflects autonomic dysfunction and inflammatory activity. Serial thermographic scans provide a non-invasive method to track disease activity and therapeutic response, particularly in early-stage CRPS where vascular dysregulation precedes structural deterioration.

Fluorescence Imaging for Inflammation (2022–2025)
Emerging optical imaging methods are being explored to visualize superficial inflammatory patterns and tissue perfusion shifts. While still adjunctive, fluorescence imaging supports the concept that CRPS is not merely neurological—it is a visible inflammatory disorder.

Dr. Bard emphasizes that imaging does not replace clinical judgment—it augments it, transforming CRPS from a diagnosis of exclusion into a condition that can be monitored with measurable biological endpoints.

From “Rare Disorder” to Recognized Neuroimmune Disease

Between 2020 and 2024, immunological research increasingly implicated autoimmune and inflammatory mechanisms in CRPS. Autoantibody associations, elevated cytokine profiles, and small fiber neuropathy findings reframed CRPS as a neuroimmune disorder, not simply a pain syndrome. Genetic association studies (2021–2023) involving HLA polymorphisms and ion channel-related genes further support a biological susceptibility framework.

 

Comorbidity research during this period also strengthened CRPS’s links to:

·        Fibromyalgia

·        Autoimmune disorders

·        Migraine and neurovascular syndromes

·        Autonomic dysfunction disorders

·        Connective tissue disorders

·        Metabolic and inflammatory stress states

Dr. Bard notes that these associations reinforce CRPS as part of a broader spectrum of systemic neurovascular dysregulation, where the injured limb becomes the visible site of a body-wide vulnerability.

Why Imaging Matters for Treatment Strategy

Imaging is not merely diagnostic—it is strategic. By mapping inflammation, vascular tone, and nerve integrity, clinicians can:

·        Identify early-stage reversible patterns

·        Distinguish inflammatory versus ischemic disease phases

·        Monitor response to therapy

·        Adjust rehabilitation intensity

·        Detect secondary nerve compression from edema

·        Track whether pain is resolving biologically—not just symptomatically

This image-guided approach aligns with recent clinical emphasis (2022–2025) on early intervention windows. The more precisely clinicians can identify CRPS’s physiological phase, the more targeted and effective treatment becomes.

Toward Precision-Guided Pain Care

Dr. Bard views CRPS as a model condition demonstrating why pain medicine must evolve beyond symptom scoring. Modern imaging brings accountability to chronic pain care—allowing clinicians to document disease biology, validate patient experience, and adjust treatment based on measurable tissue response. CRPS is no longer best understood as a rare mystery. It is an emerging example of how neuroinflammatory disorders can be visualized, tracked, and guided through imaging-informed care.

As imaging technologies advance and interdisciplinary research continues beyond 2025, CRPS may become one of the clearest demonstrations of how diagnostic visualization transforms pain from an invisible complaint into a biologically grounded, monitorable condition—reshaping both patient trust