Neurotransmitters, Neuropathy, and Neuromuscular Stimulation

How Chemical Signaling Shapes Pain, Movement, and Recovery

By: Lennard M. Goetze, Ed.D  | Polina Dembe-Petaludis, Ph.D  | Edited by: Daniel Root

Neurotransmitters are the chemical messengers of the nervous system, responsible for transmitting signals between neurons, muscles, glands, and organs. Every movement, sensation, thought, and autonomic function depends on their precise release, reception, and clearance. Disruption in neurotransmitter signaling contributes to neurological disorders, chronic pain syndromes, neuropathy, muscular atrophy, fatigue syndromes, and impaired neuromuscular coordination.

In clinical and rehabilitation medicine, growing attention has been placed on technologies that interface with the nervous system—such as Electrical Muscle Stimulation (EMS)—to support neuromuscular recruitment, circulation, pain modulation, and functional recovery. Understanding how neurotransmitters operate at the synaptic and neuromuscular junction level provides a scientific foundation for evaluating how such technologies may assist recovery, movement retraining, and symptom management in patients with neuropathy, cancer treatment–related nerve damage, metabolic disorders, and inflammatory conditions.

This review examines what neurotransmitters are, how they relate to neuropathy, how they affect the body, whether they “die” or become dormant, and how neuromuscular technologies such as EMS interact with neurotransmitter signaling to restore functional activity.

---

What Are Neurotransmitters and What Do They Do?

Neurotransmitters are endogenous chemical messengers released from presynaptic neurons into synapses, where they bind to specific receptors on postsynaptic neurons, muscle fibers, or glandular cells. Their role is to convert electrical nerve impulses into chemical signals that carry information across synaptic gaps.

 

Major neurotransmitter classes include:

·        Acetylcholine (ACh) – essential for muscle contraction at the neuromuscular junction

·        Glutamate – primary excitatory neurotransmitter in the central nervous system

·        GABA (gamma-aminobutyric acid) – primary inhibitory neurotransmitter

·        Dopamine – involved in movement regulation, motivation, reward, and executive function

·        Serotonin – regulates mood, sleep, pain perception, and autonomic balance

·        Norepinephrine – modulates alertness, vascular tone, and stress response

At the neuromuscular junction, acetylcholine plays a dominant role. When a motor neuron fires, acetylcholine is released into the synaptic cleft, binding to receptors on muscle fibers and triggering contraction. Any disruption in this signaling pathway—whether through nerve damage, receptor dysfunction, inflammatory injury, or metabolic toxicity—can impair strength, coordination, and sensory function.

---

Neurotransmitters and Neuropathy

Neuropathy refers to damage or dysfunction of peripheral nerves, commonly caused by diabetes, chemotherapy, autoimmune disease, infections, vitamin deficiencies, toxic exposure, or chronic inflammation. Neuropathic injury alters both electrical conduction and chemical neurotransmission.

 

In neuropathy:

· Sensory neurotransmitters involved in pain signaling (such as glutamate and substance P) may become dysregulated, leading to chronic burning or tingling pain.

· Motor neurotransmission may be impaired, reducing acetylcholine release or receptor sensitivity, resulting in weakness, muscle wasting, and reduced reflexes.

· Autonomic neurotransmitters that regulate circulation and temperature may be disrupted, leading to poor microvascular perfusion and delayed tissue repair.

Importantly, neuropathy is not solely a problem of “dead nerves.” In many cases, nerve fibers remain structurally present but functionally impaired. Reduced neurotransmitter release, altered receptor sensitivity, impaired mitochondrial energy production, and inflammatory signaling cascades all contribute to functional nerve failure without complete nerve death.

Myelin, the lipid-rich sheath insulating peripheral and central nerve fibers, plays a critical role in the speed and fidelity of neural signal transmission. In many neuropathies—particularly diabetic, chemotherapy-induced, and autoimmune forms—demyelination and myelin thinning impair conduction velocity and disrupt signal timing at the neuromuscular junction. This degradation does not necessarily indicate neuronal death, but rather compromised signal efficiency. As myelin integrity declines, neurotransmitter release may become dysregulated and motor unit recruitment less coordinated. Neuromuscular activation strategies, including EMS, do not repair myelin directly, but may help preserve functional pathways, support circulation, and reduce secondary degeneration by maintaining patterned neural activation during periods of compromised conduction.

Do Neurotransmitters Die or Become Dormant?

Neurotransmitters themselves do not “die.” They are synthesized, released, recycled, and degraded in continuous cycles. What can deteriorate is:

·        The neuron producing the neurotransmitter

·        The synapse’s structural integrity

·        The receptor’s responsiveness

·        The metabolic environment needed to sustain neurotransmitter production

In neuropathy and neurodegenerative conditions, signaling pathways may become functionally “dormant” due to reduced neural firing, impaired circulation, mitochondrial dysfunction, oxidative stress, or inflammatory injury. This creates a state where nerves and muscles exist anatomically but are under-stimulated and under-recruited.

This dormant-like state is reversible in some cases, particularly when neural pathways remain intact but inactive. Rehabilitation strategies aim to re-engage these pathways through mechanical loading, sensory input, neuromuscular activation, circulation enhancement, and metabolic support.

 

---

Electrical Muscle Stimulation (EMS) and Neurotransmitter Activation

Electrical Muscle Stimulation (EMS) applies controlled electrical impulses to peripheral nerves and muscle fibers, bypassing voluntary motor pathways to induce muscle contraction. At a physiological level, EMS:

·        Activates motor neurons, triggering acetylcholine release at the neuromuscular junction

·        Enhances neuromuscular recruitment patterns

·        Improves local blood flow and oxygen delivery

·        Stimulates proprioceptive feedback to the central nervous system

·        Engages neuroplastic mechanisms through repeated activation

EMS does not replace neurotransmitters—it leverages them. The electrical impulse initiates neural firing, which then triggers normal chemical neurotransmission. This is particularly relevant in patients with partial nerve dysfunction, post-surgical atrophy, cancer-related deconditioning, diabetic neuropathy, and immobilization-related muscle loss.

By repeatedly activating dormant neuromuscular pathways, EMS may help preserve receptor sensitivity, maintain synaptic integrity, and support neurovascular coupling. However, EMS is not a cure for neuropathy. Its role is supportive: maintaining neuromuscular engagement, preventing disuse atrophy, enhancing circulation, and supporting rehabilitation protocols under clinical guidance.

---

Managing Neurotransmitter Function to Restore Performance

Optimizing neurotransmitter function is not about “boosting chemicals” but restoring the biological environment that allows signaling to function properly. Evidence-based supportive strategies include:

1.     Metabolic and Nutritional Support
Neurotransmitter synthesis depends on amino acids, B vitamins (B1, B6, B12), magnesium, and iron. Deficiencies impair nerve conduction and synaptic function.

2.     Circulatory and Microvascular Support
Adequate blood flow delivers oxygen and substrates necessary for neurotransmitter production and nerve repair. Imaging of microvascular compromise (e.g., Doppler, thermal imaging) can help guide intervention strategies.

3.     Neuromuscular Activation
Movement therapies, EMS, vibration platforms, and physical rehabilitation retrain neural circuits through repeated activation.

4.     Inflammation Control
Chronic inflammation degrades synaptic health and neurotransmitter balance. Anti-inflammatory strategies (clinical nutrition, metabolic stabilization, and physical conditioning) protect signaling pathways.

5.     Neuroplastic Stimulation
Repeated sensory and motor activation promotes synaptic remodeling, preserving functional neural networks even in damaged systems.

---

Conclusion

Neurotransmitters represent the biochemical language of movement, sensation, and repair. In neuropathy and chronic disease states, neurotransmitter signaling is disrupted not because the system “dies,” but because metabolic, vascular, and inflammatory conditions impair neural function. Technologies such as Electrical Muscle Stimulation operate within this biological framework by activating neuromuscular circuits, preserving synaptic signaling, and supporting rehabilitation in patients with partial neural compromise.

When integrated into a clinically guided, evidence-based model—including imaging validation, metabolic support, circulation enhancement, and movement retraining—neuromuscular stimulation technologies serve as functional tools for preserving performance, restoring activity, and supporting recovery. The future of neurorehabilitation lies not in isolated devices, but in image-guided, physiologically grounded protocols that respect the complex chemical–electrical language of the nervous system.

 

 

PART 2:

Diagnostic Imaging, Neuropathy Detection, and Neuromuscular Activation

A Clinical Perspective from Dr. Robert L. Bard, MD, DABR, FAIUM, FASLMS

From a diagnostic imaging perspective, neuropathy and neuromuscular dysfunction are not abstract neurological events—they manifest as measurable, observable changes in tissue perfusion, nerve-adjacent inflammation, muscular architecture, vascular integrity, and biomechanical performance. Dr. Robert L. Bard’s clinical approach emphasizes that pain, weakness, numbness, and functional decline must be documented, quantified, and monitored through imaging before and after any intervention intended to influence neuromuscular recovery.

Rather than relying solely on symptom reports or performance claims, Dr. Bard’s diagnostic model integrates ultrasound, Doppler flow studies, thermal imaging, and fluorescence-based inflammatory mapping to characterize neuropathic patterns and monitor physiological response to neuromuscular activation protocols. This approach frames technologies such as Electrical Muscle Stimulation (EMS) not as standalone solutions, but as functional tools whose value must be validated through measurable tissue response and neurovascular change.

---

Imaging Neuropathy: What Can Be Seen and Measured

Peripheral neuropathy often presents clinically as sensory loss, burning pain, paresthesia, weakness, and impaired coordination. However, these symptoms are downstream effects of physiological changes that can be imaged.

From Dr. Bard’s diagnostic framework, key observable features include:

·        Microvascular compromise
Doppler ultrasound frequently reveals reduced arterial flow, venous congestion, or perfusion asymmetry in neuropathic regions. Compromised circulation impairs neurotransmitter synthesis, mitochondrial energy production, and nerve repair capacity.

·        Inflammatory signaling patterns
Thermal imaging and fluorescence-based inflammation mapping may demonstrate regional heat signatures or inflammatory patterns corresponding to nerve irritation, entrapment zones, or post-treatment tissue stress.

·        Muscle quality and architecture
High-resolution ultrasound can document muscle thinning, fiber disorganization, and fascial changes associated with denervation, disuse atrophy, or chronic pain avoidance patterns.

·        Sentinel organ responses
Distal regions such as the feet, hands, and dermal tissue often serve as sentinel zones for systemic neuropathy, toxic burden, metabolic disease, or inflammatory stress. These peripheral changes frequently precede overt neurological decline.

Dr. Bard emphasizes that neuropathy should be documented as a neurovascular and tissue-level disorder, not solely as a nerve conduction abnormality. This broader view supports integrated rehabilitation strategies that address circulation, inflammation, and neuromuscular recruitment simultaneously.

---

Neurotransmission, Muscle Activation, and Imaging Correlates

At the neuromuscular junction, acetylcholine-mediated signaling drives muscle contraction. When neuropathy disrupts neural signaling, muscles become under-recruited, leading to progressive atrophy, vascular stagnation, and connective tissue stiffening. Imaging reveals these downstream effects long before severe functional loss is clinically apparent.

 

Dr. Bard’s approach links imaging findings to neurotransmitter function indirectly:

· Poor perfusion correlates with impaired metabolic support for neurotransmitter synthesis.

· Chronic inflammation correlates with receptor dysregulation and synaptic inefficiency.

·  Structural muscle changes correlate with prolonged under-stimulation of motor units.

Neuromuscular activation protocols, including EMS-based technologies reintroduce patterned stimulation to dormant neuromuscular pathways. From a diagnostic standpoint, the question is not whether a muscle contracts during stimulation, but whether measurable physiological changes occur over time—including improved perfusion, reduced inflammatory signatures, and improved muscle architecture.

---

EMS as a Functional Input, Not a Therapeutic Endpoint

Dr. Bard’s diagnostic model places EMS within a validation framework rather than a marketing narrative. EMS is understood as a neuromuscular input that triggers physiological responses, which must then be verified through imaging and functional metrics.

When used appropriately and under clinical supervision, EMS protocols may demonstrate measurable correlates such as:

·        Improved microvascular flow on Doppler imaging

·        Reduction of localized inflammatory thermal signatures

·        Improved muscle density and fiber organization on ultrasound

·        Enhanced venous return and tissue oxygenation patterns

·        Improved symmetry between affected and unaffected limbs

However, EMS does not repair damaged nerves, regenerate neurons, or reverse advanced neuropathy. Its clinical value lies in:

·        Preventing disuse-related degeneration

·        Supporting circulation in compromised regions

·        Maintaining neuromuscular signaling integrity

·        Serving as a bridge during rehabilitation, recovery, and metabolic stabilization

Dr. Bard emphasizes that EMS outcomes must be documented longitudinally. Without imaging validation, any performance claims remain anecdotal.

---

Imaging-Guided Neuromuscular Activation Protocols

A central theme in Dr. Bard’s diagnostic philosophy is that neuromuscular activation protocols should be personalized based on imaging findings. A standardized EMS program applied indiscriminately to neuropathic patients may fail to address the underlying pathology driving dysfunction.

An imaging-guided framework may include:

1.     Baseline Mapping
Ultrasound and Doppler imaging to assess muscle quality, vascular supply, and structural asymmetries.
Thermal or fluorescence imaging to identify inflammatory zones or neurovascular stress patterns.

2.     Targeted Activation Planning
EMS protocols selected based on regional perfusion deficits, muscle recruitment gaps, and biomechanical imbalance patterns.

3.     Sequential Monitoring
Periodic imaging to evaluate changes in perfusion, inflammation, and tissue architecture over time.

4.     Functional Correlation
Pairing imaging findings with clinical outcomes such as pain reduction, gait stability, strength symmetry, and endurance tolerance.

This model shifts neuromuscular activation from generalized wellness intervention into a measurable, evidence-based adjunct to rehabilitation and chronic disease management.

---

Neuropathy in Chronic Disease and Oncology Populations

Dr. Bard’s imaging work frequently intersects with cancer patients, metabolic disease populations, and individuals exposed to neurotoxic treatments or environmental burden. Chemotherapy-induced neuropathy, diabetic neuropathy, and toxin-associated neural injury present overlapping imaging patterns—microvascular compromise, inflammatory stress, and progressive neuromuscular underuse.

In these populations, neuromuscular activation technologies may serve as supportive tools for:

·        Preserving muscle integrity during periods of systemic illness

·        Supporting circulation in compromised extremities

·        Mitigating secondary functional decline

·        Supporting rehabilitation when voluntary exercise tolerance is limited

Once again, Dr. Bard underscores that these interventions must be framed within diagnostic accountability—using imaging to confirm whether physiological improvement is occurring.

---

Conclusion

From Dr. Robert Bard’s diagnostic perspective, neuropathy is a measurable neurovascular and tissue-level disorder that extends beyond nerve conduction abnormalities alone. Imaging technologies provide the objective framework needed to detect early dysfunction, characterize inflammatory and circulatory contributors, and validate the physiological impact of neuromuscular activation strategies.

Technologies such as EMS, PEMF, TENS, shockwave therapy, low-level laser / photobiomodulation, vibration platforms, therapeutic ultrasound, and localized thermal or cryotherapy systems may serve as functional inputs to re-engage dormant neuromuscular pathways, support microvascular circulation, modulate inflammatory signaling, and preserve muscle integrity. However, their clinical value depends on objective verification through imaging-guided monitoring and physiological outcome measures rather than anecdotal performance claims.

The future of neuromuscular rehabilitation lies in image-guided activation protocols, where diagnostic intelligence directs intervention strategy, and physiological response—not perception alone—defines success.

 

PROOF VS. HEARSAY

 

ANECDOTAL vs. EVIDENCE-BASED CLAIMS: Why Measurable Proof Must Guide Modern Clinical Decisions

By: Lennard M. Goetze, Ed.D

In today’s health landscape, stories travel faster than science. Personal testimonials, social media endorsements, and word-of-mouth success stories often shape public perception of treatments, devices, and wellness protocols. While such anecdotes can be emotionally compelling, they are not the same as evidence. The distinction between anecdotal claims and evidence-based validation is not merely academic—it is foundational to ethical, effective, and responsible clinical care.

Anecdotal evidence refers to personal accounts or individual experiences that lack systematic data collection, controls, or reproducibility. These stories may be sincere and meaningful to the individuals who share them, but they cannot reliably establish cause-and-effect relationships. One patient’s improvement does not prove a treatment’s efficacy; it may reflect placebo effects, natural disease variation, concurrent interventions, or regression to the mean. In contrast, evidence-based claims arise from structured inquiry: controlled studies, measurable outcomes, standardized protocols, and peer-reviewed validation. This approach anchors medical decision-making in reproducible findings rather than impressions.

The Limits of “I Feel Better” as Proof

Subjective improvement—“I feel good,” “my pain is less,” “my energy improved”—is an important part of patient-centered care, but it is not proof of therapeutic efficacy. Symptoms fluctuate. Chronic conditions wax and wane. Psychological factors, expectations, and supportive environments can influence perceived outcomes. Without objective metrics, it is impossible to distinguish between a true physiological change and a coincidental or placebo-driven response.

Evidence-based medicine does not dismiss patient experience; rather, it contextualizes it. The patient voice informs hypotheses, identifies unmet needs, and shapes clinical priorities. However, claims that aim to influence clinical practice, public policy, reimbursement, or widespread adoption must be supported by measurable endpoints—quantitative data, imaging correlates, biomarkers, functional outcomes, and longitudinal tracking. When claims outpace proof, credibility erodes and patients bear the risk.

Why Validation Matters in Modern Diagnostics

Contemporary diagnostics increasingly rely on technologies capable of generating quantifiable, reproducible data—advanced ultrasound, Doppler flow analysis, elastography, thermographic pattern analysis, spectrophotometry-based screening, and retinal microvascular imaging, among others. The strength of these tools lies not in novelty, but in their capacity to produce measurable signals that can be tracked over time and compared across populations.

Within this framework, the philosophy guiding clinicians like Dr. Robert Bard emphasizes disciplined interpretation of imaging and physiologic data rather than reliance on subjective impressions. The clinical value of any diagnostic modality depends on defined protocols, standardized acquisition methods, inter-reader reliability, and correlation with known disease processes. Validation is not a marketing exercise; it is a scientific obligation. Technologies must demonstrate sensitivity, specificity, predictive value, and clinical relevance through structured studies and real-world performance tracking.

Quantitative Data as a Safeguard Against Overclaiming

Evidence-based validation serves as a safeguard against overstatement and misinterpretation. Quantitative diagnostics allow clinicians to move beyond “it seems to help” toward “we can measure change.” This includes:

·   Baseline-to-follow-up comparisons: Demonstrating objective change over time.

·   Correlative findings: Linking imaging features or biomarkers with clinical endpoints.

·   Reproducibility: Showing consistent results across operators and settings.

·   Outcome relevance: Establishing that detected changes meaningfully relate to patient health, function, or risk.

When protocols incorporate blinded reads, standardized scoring, and pre-defined outcome measures, claims become testable. If findings fail to replicate, they can be refined or retired. This self-correcting nature of evidence-based practice is a strength, not a weakness. It protects patients from premature conclusions and clinicians from well-intentioned but unsupported assertions.

The Role of Validation Studies in Responsible Innovation

Innovation in diagnostics and integrative care often emerges ahead of large-scale randomized trials. Early-stage validation studies—pilot cohorts, feasibility studies, correlation analyses—play a critical role in determining whether a promising signal warrants broader investigation. Responsible clinicians advocate for incremental validation: first establishing technical reliability, then clinical correlation, and finally outcome relevance. This progression builds a bridge between exploratory innovation and accepted standards of care.

In this context, Dr. Bard’s approach underscores the importance of image-guided assessment as a complement to clinical evaluation. The emphasis is not on replacing established diagnostic pathways, but on adding objective layers of insight that can inform screening, second opinions, surveillance, and treatment planning. The credibility of such approaches rests on transparent methods, clearly defined limitations, and continuous comparison with established benchmarks.

Evidence as a Trust-Building Practice

Public trust in healthcare is fragile. Overpromising erodes confidence, especially when claims are later contradicted by rigorous studies. Evidence-based communication—clear about what is known, what is probable, and what remains unproven—builds durable trust. This means acknowledging uncertainty, reporting negative findings, and resisting the temptation to extrapolate beyond available data.

Clinicians and institutions that prioritize validation signal respect for patients’ right to informed decision-making. They also contribute to a culture where innovation is measured by outcomes rather than enthusiasm alone. In this model, patient-reported improvements are welcomed as signals to investigate further—not as endpoints that replace scientific confirmation.

Conclusion: From Stories to Standards

Anecdotes can inspire inquiry, but they cannot define standards of care. The transition from “I feel better” to “we can measure meaningful change” is the difference between belief and evidence. Modern clinical practice demands verifiable data, reproducible methods, and transparent validation. When diagnostic and therapeutic claims are grounded in measurable outcomes and peer-informed protocols, they serve patients, clinicians, and the broader healthcare ecosystem with integrity.

The philosophy of evidence-based validation—exemplified by disciplined, image-guided diagnostic approaches—does not diminish the human story of healing. It honors it by ensuring that claims about care are supported by proof. In a world crowded with testimonials, science remains the most reliable advocate for truth.

 

SOURCE VS RESOURCE

THE CANCER DETECTIVE: Dr. Robert Bard’s 40-Year Legacy of Seeing What Others Miss

In the quiet glow of a desk lamp, a vintage photograph rests in the foreground—an earlier version of Dr. Robert L. Bard, composed, focused, unmistakably analytical. In the background, the present-day Dr. Bard gestures mid-conversation, animated and engaged, still driven by the same question that has defined four decades of clinical life: What is the body trying to tell us—and how can we learn to see it more clearly?

This image captures more than the passage of time. It reflects a rare continuity of purpose. For over 40 years, Dr. Bard has built a reputation as “The Cancer Detective,” not for chasing headlines, but for refining the art and science of diagnostic interpretation—listening to subtle signals, correlating imaging with physiology, and connecting clinical dots others often overlook.

Dr. Bard’s journey began with disciplined service in the military, where early exposure to high-pressure clinical environments shaped his diagnostic mindset: accuracy matters, context matters, and every data point has meaning when lives are at stake. That foundation carried into his civilian medical career, where he trained and practiced as a radiologist with a singular fascination for how disease reveals itself before it declares itself.

Over time, his clinical work expanded beyond conventional imaging workflows. Dr. Bard became known for reading pathology not as isolated snapshots, but as evolving patterns. In oncology, this meant helping clinicians understand tumor behavior, vascular involvement, inflammatory changes, and tissue response—often guiding decision-making in complex cancer cases. His work across breast cancer, prostate cancer, and male breast cancer has emphasized early detection, careful monitoring, and image-guided interpretation as a way to personalize care.

Yet Dr. Bard’s legacy is not confined to the reading room. He is equally recognized for his contributions to medical education and publishing—transforming technical diagnostics into accessible knowledge for clinicians, patients, and multidisciplinary teams. Through books, articles, interviews, and teaching initiatives, he has consistently translated complex imaging concepts into practical clinical insight.

That educational mission evolved into programmatic innovation. Over the years, Dr. Bard helped shape and champion multiple initiatives that connect diagnostic imaging with preventive and functional medicine. Programs such as DetoxScan, ThyroidScan, PodiatryScan, DermalScan, ProstateScan, and BreastScan reflect a unifying philosophy: the body leaves clues across organ systems, and imaging can serve as a bridge between symptoms, exposure history, and measurable physiology. These platforms encourage clinicians to use non-invasive imaging as part of baseline assessment, follow-up care, and evidence-guided prevention strategies.

His philanthropic work through the AngioInstitute extends this impact further—supporting education, research collaboration, and public awareness around diagnostic innovation and early detection. Here, Dr. Bard’s role is not only that of a clinician, but of a builder of ecosystems—bringing together physicians, technologists, educators, and advocates to strengthen how medicine sees disease.

Now, as the release of his latest biography, The Eye Within: Mastering Cancer Through the Art of Medical Imaging Interpretation, marks a new chapter, Dr. Bard’s legacy comes into sharper focus. The book is not a victory lap. It is a reflection on how diagnostic excellence is cultivated over time—through curiosity, humility, pattern recognition, and respect for the body’s signals. It documents a career spent refining the ability to see beneath the surface, reminding readers that interpretation is as vital as technology itself.

The photograph tells the story quietly: the young diagnostician captured in sepia tones, and the seasoned physician still in motion decades later. The tools have evolved. The technologies have advanced. But the mission remains unchanged. Dr. Robert Bard’s 40-year legacy is not simply about detecting cancer—it is about teaching medicine how to look again, more carefully, more compassionately, and with a deeper respect for what the body reveals when we learn how to see.

 

  

DETECTIVE WORK IN MEDICINE

INFLAMMATION: The Clinical Reality Behind the word "PAIN"

Pain is one of the most commonly reported symptoms in medicine—and one of the least precise. Patients describe pain using words like burning, stabbing, throbbing, or aching. Clinicians attempt to quantify it with subjective scales such as “rate your pain from one to ten.” While these tools are useful for understanding a patient’s experience, pain itself remains an internal sensation: personal, anecdotal, and impossible to measure directly. No clinician can see pain. No instrument can quantify it. Pain is a feeling, not a clinical marker.

What medicine can see, measure, and document is inflammation.

Inflammation is the biological process that often underlies pain. It is a visible, measurable, and evidence-reportable phenomenon reflecting tissue stress, immune activation, vascular response, and cellular injury. Unlike pain, inflammation leaves physical footprints—edema, vascular congestion, thermal changes, tissue thickening, hyperemia, and altered perfusion patterns. These changes can be documented through imaging technologies such as diagnostic ultrasound, Doppler flow analysis, and thermal imaging, offering clinicians a tangible target for investigation and intervention.

This distinction matters. Treating “pain” alone risks addressing symptoms without understanding the underlying pathology. Pain may originate from neuropathic injury, ischemia, inflammatory cascades, mechanical compression, autoimmune reactions, or toxic burden. Without objective markers, clinical decision-making is forced to rely on trial-and-error therapies and patient-reported outcomes that fluctuate with perception, tolerance, and emotional state. In contrast, identifying inflammation allows clinicians to localize dysfunction, track disease progression, monitor treatment response, and adjust care using measurable data.

Modern diagnostic imaging has reframed how inflammation is detected and followed. High-resolution ultrasound can visualize soft-tissue changes, tendon thickening, joint effusions, nerve sheath irritation, and microvascular congestion associated with inflammatory activity. Doppler imaging can demonstrate altered blood flow patterns linked to inflammatory processes. These findings provide clinicians with directional intelligence: where pathology exists, how extensive it is, and whether it is improving or worsening over time. In this context, imaging transforms a patient’s report of “pain” into a clinically actionable map of inflammation.

This approach also improves the quality of evidence in therapeutic evaluation. Claims of improvement based solely on subjective pain relief—“I feel better”—are vulnerable to placebo effects, temporary masking of symptoms, or adaptation. Objective imaging markers of inflammation offer measurable endpoints: reduction in tissue swelling, normalization of vascular flow, and restoration of structural integrity. These markers support responsible validation of treatments and guide clinicians toward precision-based care rather than anecdotal reassurance.

A persistent barrier in therapeutic development is the regulatory discomfort with the word “pain” as a primary clinical endpoint. In regulatory science, agencies such as the U.S. Food and Drug Administration prioritize measurable, objective, and reproducible outcomes. “Pain” as a claim is inherently subjective, varies widely between individuals, and lacks a direct biomarker, making it a weak foundation for validation, labeling, and approval. As a result, developers of drugs, devices, and pain-management technologies often face costly delays or rejections when their evidence is built primarily on patient-reported pain relief rather than demonstrable physiological change. Labeling something as “painful” is descriptive language—an adjective and a patient experience—not a clinical metric. Regulatory pathways increasingly demand quantifiable correlates such as reduced inflammation, improved tissue integrity, restored perfusion, or documented functional recovery. This shift reflects a broader movement in evidence-based medicine: therapies are more likely to gain approval when they demonstrate measurable biological impact rather than relying on subjective symptom reporting alone.

Reframing pain through the lens of inflammation does not diminish the patient’s experience. Instead, it strengthens clinical care by anchoring symptoms to observable pathology. Pain is real to the patient. Inflammation is real to the clinician. When medicine prioritizes what can be seen, measured, and documented, it moves closer to evidence-driven diagnosis, targeted intervention, and accountable outcomes.

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.

---

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

---

 

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.

---

SPONSORED AD:

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.

---

 

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.

---

  

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.

---

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.

---

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.

---

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