Chronic Pain: A Neurological Approach
Chronic pain that persists beyond tissue healing is not a musculoskeletal problem. It is a neurological one. When the central nervous system learns to amplify, sustain, and generate pain signals independent of peripheral input, the diagnosis belongs in neurology—and so does the treatment. We evaluate chronic pain as a disorder of the brain and spinal cord, not as a billing code for more injections.
Central Sensitization: When the Brain Becomes the Pain Generator
In a healthy nervous system, pain is a proportional response to a noxious stimulus. Tissue damage activates peripheral nociceptors, the signal travels through the dorsal horn of the spinal cord, and the brain registers the experience at a level that matches the severity of the input. When the injury heals, the signal stops. That is how the system is supposed to work.
Central sensitization is what happens when it doesn’t. In this state, the dorsal horn neurons become hyperexcitable. NMDA receptors upregulate, lowering the threshold for activation. Wind-up occurs—a progressive increase in action potential firing from repeated C-fiber input that leaves second-order neurons in a state of sustained depolarization. The result is pain that persists after the peripheral stimulus has resolved, pain that spreads beyond the original injury site, and pain triggered by stimuli that should not hurt at all.
Clifford Woolf described this mechanism in his landmark 2011 review in Pain, identifying central sensitization as a distinct clinical entity driven by altered synaptic processing in the spinal cord and brain. Latremoliere and Woolf (2009, The Journal of Pain) further characterized the molecular cascades involved: phosphorylation of NMDA and AMPA receptor subunits, activation of intracellular kinase pathways including PKC and ERK, and loss of GABAergic and glycinergic inhibitory tone in the dorsal horn. These are not abstract laboratory findings. They explain why a patient’s MRI can look normal while their experience of pain is devastating.
Descending inhibition failure compounds the problem. Under normal conditions, brainstem nuclei—the periaqueductal gray, the rostral ventromedial medulla—send inhibitory signals down the spinal cord that modulate incoming pain transmission. In centrally sensitized patients, this top-down brake weakens or reverses, allowing pain signals to pass through the dorsal horn with less filtering. The patient doesn’t just feel more pain. Their nervous system has lost the capacity to turn the volume down.
This is why opioids fail in central sensitization. Opioids act primarily on mu receptors in the peripheral and central nervous system to suppress nociceptive transmission. But when pain is being generated by NMDA-driven synaptic plasticity and disinhibited spinal circuits, mu-receptor agonism does not address the mechanism. Escalating opioid doses in these patients produces tolerance and dependence without resolving the underlying neuroplastic changes that maintain the pain state.
CRPS and Neuroinflammatory Pain
Complex regional pain syndrome is among the most severe chronic pain conditions a neurologist encounters. It typically develops after an injury—a fracture, a surgery, a soft tissue trauma—and presents with pain that is wildly disproportionate to the inciting event. The affected limb may show edema, color changes, temperature asymmetry, trophic changes to the skin and nails, and motor dysfunction. In advanced cases, the pain spreads to contralateral limbs or becomes generalized.
The Budapest criteria, codified by Harden et al. (2010, Pain Medicine), established the current diagnostic framework for CRPS. Diagnosis requires continuing pain disproportionate to the inciting event, plus signs and symptoms across at least three of four categories: sensory (allodynia, hyperalgesia), vasomotor (temperature or color asymmetry), sudomotor/edema (swelling, sweating changes), and motor/trophic (weakness, tremor, dystonia, skin or nail changes). The criteria were designed to balance sensitivity and specificity, but in practice, CRPS remains underdiagnosed because many clinicians are unfamiliar with the full spectrum of its presentation.
The pathophysiology of CRPS involves a convergence of peripheral and central mechanisms. Neurogenic inflammation mediated by substance P and CGRP produces the vasomotor and sudomotor changes. Sympathetic-afferent coupling creates a loop in which sympathetic nervous system activity drives nociceptor activation. And central sensitization, the same NMDA-driven process described above, amplifies and sustains the pain signal long after the original injury has healed. Autoimmune mechanisms have also been implicated: antibodies against autonomic nervous system receptors have been identified in a subset of CRPS patients, suggesting that the immune system can directly attack the neural infrastructure that regulates blood flow and pain in the affected limb.
Evaluating CRPS properly requires a neurologist who understands both the peripheral and central components. Treating only the limb while ignoring the brain’s role in maintaining the pain state is why so many CRPS patients cycle through nerve blocks, sympathectomies, and spinal cord stimulators without meaningful relief.
Why Standard Pain Management Falls Short
The typical pain clinic operates on a procedural model. Patients arrive with pain. They receive an MRI of the relevant spine segment. If a structural abnormality is found, an injection is offered. If the injection fails, a different injection is tried, or a stimulator is discussed, or opioids are prescribed at escalating doses. The neurological workup that should precede any of these interventions is rarely performed.
This model works for acute, nociceptive pain with a clear structural generator—a herniated disc pressing on a nerve root, an inflamed facet joint, a torn rotator cuff. It fails badly when the pain is being driven by central sensitization, neuroinflammation, autonomic dysfunction, or post-traumatic neuroplastic changes. In those cases, the MRI may be unremarkable, the injections may provide only days of relief, and the patient is gradually reclassified as a chronic pain patient who “needs to manage expectations.”
The missing step is the neurological evaluation. No one has assessed whether the dorsal horn is hyperexcitable. No one has tested descending inhibition. No one has measured whether the patient’s pain thresholds have shifted in a pattern consistent with central sensitization. No one has checked autonomic function for the sympathetic dysfunction that drives CRPS. Without these data, every treatment is empirical—a guess informed by anatomy rather than by the actual mechanism producing the pain.
Post-concussive persistent pain deserves particular attention in this context. Patients with traumatic brain injury frequently develop chronic headaches, neck pain, and widespread body pain that does not respond to the musculoskeletal interventions their primary care doctors prescribe. The reason is straightforward: the pain is neurological. It is generated or amplified by injured cortical and brainstem circuits, not by damaged muscles or joints. Treating these patients in a pain clinic without a concurrent neurological evaluation is treating the symptom while ignoring the organ that produces it. Learn more about our approach to brain injury on our traumatic brain injury page.
Treatments We Use for Neurological Chronic Pain
Each therapy targets a specific mechanism in the chronic pain pathway. The combination and sequencing are determined by diagnostic findings, not by a standard protocol.
Occipital Nerve Block
Targeted peripheral nerve blocks silence specific pain generators and reduce afferent input to sensitized central circuits. Diagnostic blocks also help identify which peripheral structures are contributing to the overall pain state.
NAD+ IV Therapy
NAD+ restores mitochondrial function in neurons stressed by chronic inflammatory signaling. Adequate NAD+ levels support sirtuin-mediated anti-inflammatory pathways and cellular repair mechanisms that are depleted in persistent pain states.
NeuroCoaching
Chronic pain rewires behavior, sleep, and cognition. Dr. Edwards works with patients on pain catastrophizing, sleep hygiene, activity pacing, and the cognitive patterns that reinforce central sensitization through fear-avoidance and hypervigilance.
Our Diagnostic Approach
Before we treat chronic pain, we identify the mechanism producing it. Each diagnostic tool answers a specific question about where the signal is being generated or amplified.
Advanced Neuroimaging
Functional MRI and PET scanning reveal pain-processing abnormalities that structural imaging misses. We assess cortical thickness in somatosensory and insular cortex, connectivity between the pain matrix and prefrontal regulatory regions, and metabolic activity in brainstem pain-modulation centers.
Quantitative Sensory Testing
QST maps thermal and mechanical detection and pain thresholds across dermatomes. Shifted thresholds and temporal summation patterns provide objective evidence of central sensitization and help distinguish neuropathic from nociceptive pain mechanisms in patients with ambiguous presentations.
Autonomic Testing
Sympathetic skin response, heart rate variability, and sudomotor testing evaluate the autonomic nervous system dysfunction that drives vasomotor and trophic changes in CRPS and that contributes to pain amplification through sympathetic-afferent coupling.
Inflammatory & Neuroinflammatory Panels
Blood panels measuring high-sensitivity CRP, IL-6, TNF-alpha, and neurofilament light chain identify systemic and neuroinflammatory contributions to the pain state. These markers guide anti-inflammatory components of the treatment protocol and provide objective measures for tracking response over time.
Frequently Asked Questions
How is a neurological approach to chronic pain different from a pain clinic?+
What conditions do you treat under chronic pain?+
What diagnostic tests do you use for chronic pain evaluation?+
Do you prescribe opioids for chronic pain?+
How long does the chronic pain evaluation take?+
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Chronic Pain Deserves a Neurological Workup
If you’ve been through pain clinics, opioid tapers, and injections that don’t hold—the problem may not be where anyone has been looking. Dr. Orr evaluates chronic pain as a disorder of the central nervous system and builds a treatment plan around what the diagnostics actually show. The Neurogenesis Project is accepting new patients in St. Marys, Georgia.