Diagnosing Centralized Pain After Peripheral Nerve Injury: The 2026 Raasveld-Eberlin Framework

By Dr. Chris Lakhiani, MD, FACS · August 2026

1. The Clinical Problem

1.1 Prevalence and impact of chronic pain after PNI

Chronic pain following peripheral nerve injury is common and undertreated. Depending on injury mechanism and surgical context, persistent neuropathic pain occurs in a substantial minority to majority of patients, with rates approaching 30–50% after nerve transection, iatrogenic injury, or major limb trauma, and lower but still clinically significant rates after elective decompression.^2,3 A meaningful subset of these patients develop pain that is disproportionate to residual peripheral pathology, extends beyond the injured nerve's territory, and does not respond as expected to further peripheral treatment. Recognizing this centralized phenotype is a prerequisite to appropriate care.

1.2 Historical terminology and its costs

The literature has used overlapping and sometimes conflicting labels for this phenomenon: centralized pain, central sensitization, nociplastic pain, chronic post-surgical pain (CPSP), and complex regional pain syndrome (CRPS).^4,5,6 Each term captures part of the picture. Central sensitization refers to a defined neurophysiological process — an increase in the responsiveness of central nociceptive neurons to normal or subthreshold afferent input.^7,8 Nociplastic pain is a mechanistic IASP descriptor for pain arising from altered nociception without clear evidence of tissue damage or lesion of the somatosensory system.^9,10 Centralized pain is a broader clinical construct describing pain whose primary driver has shifted from peripheral to central. The lack of a shared, surgically operationalized definition has contributed to variable identification, inconsistent research inclusion criteria, and — most importantly for the practicing surgeon — inconsistent selection of patients for further peripheral intervention.

1.3 The surgeon's dilemma

Surgeons evaluating a patient with persistent pain after nerve injury or nerve surgery are asked to decide whether additional peripheral treatment — revision decompression, neurolysis, neuroma excision, targeted muscle reinnervation, or regenerative peripheral nerve interfaces — is likely to produce meaningful, durable relief. The stakes of misclassification are high in both directions. Missing a treatable peripheral generator commits a patient to years of unnecessary suffering; operating on a patient whose pain is now primarily centrally maintained risks a technically successful operation with a clinically disappointing outcome and, at times, a worsened pain state. A shared diagnostic framework that identifies centralization does not replace clinical judgment, but it constrains it usefully. For a related discussion of the limits of a normal electrodiagnostic study in peripheral nerve pain, see the earlier professional article, Peripheral Nerve Decompression for Pain with Normal Electrodiagnostics.

2. Neurophysiological Basis

2.1 NMDA-mediated wind-up and dorsal horn plasticity

Repetitive C-fiber input to the spinal dorsal horn produces temporal summation and progressive facilitation of second-order neuron responses — the classical wind-up phenomenon.^7,8 NMDA-receptor activation, removal of the magnesium block, and downstream intracellular signaling produce lasting increases in synaptic efficacy and neuronal excitability. Clinically, the result is allodynia (pain from normally innocuous input), primary and secondary hyperalgesia, aftersensations, and an expanded receptive field. These are properties of the central nervous system, not the injured peripheral tissue.

2.2 Loss of descending inhibition

Pain transmission is continuously modulated by descending projections from the periaqueductal gray, rostral ventromedial medulla, and locus coeruleus, using serotonergic, noradrenergic, and endogenous opioidergic pathways.^8,11 In chronic pain, endogenous inhibition is often impaired and descending facilitation may become disproportionate. This shift in top-down modulation is a mechanistic basis for the observed efficacy of serotonin-norepinephrine reuptake inhibitors (SNRIs) and tricyclic agents in centralized pain, and it explains why interventions targeting attention, appraisal, sleep, and mood can produce meaningful analgesic effects.

2.3 Glial activation and neuroinflammation

Microglia and astrocytes in the dorsal horn respond to peripheral nerve injury with morphologic activation, cytokine release, and altered neuronal-glial signaling.¹² The resulting neuroinflammatory cascade contributes to persistent central hyperexcitability even after the peripheral trigger has resolved. This mechanism is one reason that time-since-injury alone does not reliably predict whether continued peripheral treatment will be effective.

2.4 Extraterritorial spread as the hallmark

The single most useful bedside sign of central rather than peripheral amplification is sensory disturbance extending beyond the anatomic territory of the injured nerve.^13,14 A patient with an ulnar-nerve injury who now has hyperalgesia across the volar forearm and hand, or a patient after saphenous neuroma excision who now has widespread lower-extremity allodynia, cannot be fully explained by residual peripheral pathology alone. Extraterritorial spread is the anatomic fingerprint of central amplification and forms the third criterion of the Raasveld-Eberlin framework discussed below.

3. The Raasveld-Eberlin Systematic Review (2026)

3.1 Citation and scope

Raasveld FV, Tiems MRA, Johnston BR, Moussa O, Valerio IL, Hao D, Coert JH, Eberlin KR. Diagnostic Criteria for Centralized Pain Following Peripheral Nerve Injury: A Systematic Review. Clin J Pain. 2026;42(1):e1326. DOI: 10.1097/AJP.0000000000001326. PMID: 40977364.¹ The senior authorship (Eberlin) originates from the Hand & Arm Service, Division of Plastic and Reconstructive Surgery, Massachusetts General Hospital / Harvard Medical School and represents the first systematic effort to identify and synthesize diagnostic approaches to centralized pain specifically in the PNI population.

3.2 Methodology

The authors performed a PRISMA-guided systematic search of MEDLINE, Embase, Web of Science, and the Cochrane Central Register of Controlled Trials (CENTRAL). Screening began with 950 candidate citations; after title, abstract, and full-text review with predefined criteria, 28 studies were included in the qualitative synthesis, together encompassing 6,189 patients.¹ Exclusion criteria removed studies limited to acute pain (<3 months), pediatric populations, and non-English publications. The purpose of the synthesis was explicitly to standardize identification of centralized pain in the PNI population and to inform surgical decision-making.

3.3 Output

The review produced a five-criterion diagnostic framework derived from the recurring clinical features and diagnostic anchors reported across the included studies. Four criteria are required and one is optional but decisive when performed. The framework is offered as a clinical, not a research, tool; it is designed for use at the point of surgical consultation.

4. The Five Proposed Criteria

4.1 Documented peripheral nervous system injury or compression

The entry gate. The criterion establishes that centralization is a downstream state following an identifiable peripheral event — traumatic, iatrogenic, compressive, or otherwise. This distinguishes centralized pain following PNI from primary central pain syndromes (post-stroke central pain, spinal cord injury central pain, fibromyalgia, or centrally maintained pain without a clear peripheral trigger).¹ In practical terms, the surgeon must have anatomic or historical evidence of a peripheral event: imaging, operative history, electrodiagnostic findings, or a documented compression or injury.

4.2 Neuropathic pain persisting ≥3 months

Aligns with the IASP definition of chronic pain and excludes the acute or subacute phase during which peripheral recovery may still occur.^9,10 The three-month threshold is not magical, but it captures the observation that pain persisting beyond expected peripheral healing timelines is more likely to reflect central processes and warrants a broader diagnostic frame. The pain quality should carry neuropathic features (burning, electric, shooting, cold-hyperalgesia, paresthesia) rather than pure nociceptive characteristics.

4.3 Hyperalgesia, allodynia, or hypersensitivity extending beyond the primary zone of injury

The cardinal sign. Extraterritorial spread — sensory disturbance outside the anatomic territory of the injured nerve — implies central amplification because it cannot be explained by residual peripheral pathology alone.^13,14 Standard bedside testing should include pinprick hyperalgesia mapping, static and dynamic mechanical allodynia (brush, cotton swab), pressure algometry when available, and cold/warm perception outside the injury dermatome. A structured quantitative sensory testing (QST) evaluation is more sensitive but often impractical in a surgical clinic; a careful and consistent bedside examination is usually sufficient to identify clinically relevant spread.

4.4 Associated mood or cognitive disturbances

Depression, anxiety, sleep disturbance, and cognitive dysfunction that travel with the pain — consistent with the S.P.A.C.E. symptom cluster (Sleep, Pain, Affect, Cognition, Energy) described by Williams and colleagues in the fibromyalgia and centralized-pain literature.¹⁵ These features reflect shared neuroanatomic substrates including the limbic system, prefrontal cortex, and descending modulatory pathways. Their presence does not mean the pain is psychogenic; it means the same central circuits generating the pain are also involved in mood, sleep, and cognition, and that treating one domain without the others is unlikely to succeed.

4.5 Limited response to peripheral nerve blocks (<50% pain reduction)

Optional but decisive. Criterion #5 is functionally a physiologic test of whether peripheral input remains the dominant driver of pain. A well-placed, anatomically appropriate diagnostic block that fails to reduce pain by at least 50% argues strongly against isolated peripheral intervention on that target.¹ In the surgical setting, this is the single most operationally useful criterion, because it can convert a difficult qualitative judgment (is the pain still peripheral?) into a testable clinical observation. The criterion is optional because a block is not always necessary — some patients meet the other four criteria unambiguously — but where diagnostic uncertainty remains, the block clarifies it.

4.6 How Raasveld-Eberlin compares to existing tools

The Raasveld-Eberlin framework is not intended to replace CSI, painDETECT, DN4, or QST. It complements them by providing a surgical-population-specific, clinically brief construct that anchors the diagnosis to an anatomically appropriate diagnostic block — a maneuver already familiar to peripheral nerve surgeons and pain specialists.

5. Operational Implications for the Peripheral Nerve Surgeon

5.1 Preoperative screening for the reoperative or persistent-pain patient

Any patient presenting for consideration of revision nerve decompression, neuroma revision, repeat neurolysis, or targeted muscle reinnervation for pain should be screened against the five criteria. In practice, this can be embedded in intake as a structured checklist: (i) is there a documented peripheral event; (ii) has neuropathic pain persisted ≥3 months; (iii) is sensory disturbance limited to the injured nerve's territory or does it extend beyond; (iv) are there significant mood, sleep, or cognitive symptoms traveling with the pain; and (v) if a diagnostic block has been performed, what percentage relief was obtained and for how long. The higher the criterion count, the stronger the case for pausing before further peripheral surgery and involving pain psychology, physical therapy, and medication optimization concurrently.

5.2 The value of the diagnostic block

An anatomically appropriate peripheral block — ultrasound-guided where feasible, at a location that predictably captures the suspected target — is the most powerful tool available for distinguishing dominant peripheral from dominant central drivers.^1,20 Practical guidance:

• Anatomic accuracy is paramount. Ultrasound or fluoroscopic confirmation reduces false-negatives from technical failure. A patient who did not receive an accurate block cannot be said to have failed one.
• Document expected motor and sensory effect. Confirm that the block took effect in the appropriate distribution before interpreting the pain response.
• Quantify relief and duration. Use a numerical rating scale before, at expected peak effect, and at 30–60 minute intervals. Duration of relief should be consistent with the local anesthetic used.
• Correlate with symptom domains. Did the block relieve the burning component but not the widespread allodynia? Did it affect resting pain, movement-evoked pain, or both? Domain-specific responses inform combined treatment planning.
• Interpret with the criteria in mind. <50% pain reduction with an anatomically accurate block is the operationally decisive finding for criterion #5.

5.3 Integrating surgical and non-surgical care

Meeting the Raasveld-Eberlin criteria does not preclude surgery. When a clear peripheral generator remains — a demonstrable neuroma, an anatomically confirmed compression, an identifiable end-neuroma amenable to targeted muscle reinnervation or regenerative peripheral nerve interfaces — surgery may still be indicated. What changes is how the operation is framed and what adjunctive care is planned. The sequence I typically use:

1. Address the peripheral generator when a discrete, anatomically appropriate target exists and the block response supports it.
2. Concurrent pain-focused physical therapy: graded exposure, desensitization, restoration of movement without threat.
3. Concurrent behavioral pain intervention (pain reprocessing therapy, EAET, CBT-CP, or ACT depending on availability and patient fit).^23,25 Pain neuroscience education alone can produce meaningful shifts in threat appraisal and function when integrated with graded activity.²⁴
4. Medication adjustment: SNRIs (duloxetine, venlafaxine) and/or gabapentinoids (gabapentin, pregabalin) as first-line for neuropathic and centralized pain, tricyclic agents (nortriptyline, amitriptyline) where tolerated, avoidance of chronic opioid escalation.^21,22

For a full discussion of pain reprocessing therapy, referral pathways, and digital adjuncts appropriate to this population, see the earlier professional article, Neuroplastic Pain and the Referring Surgeon: Adjunctive Resources for Central Sensitization.

5.4 Language and shared decision-making

How the finding is framed matters as much as the finding itself. A useful phrasing: "Your pain is real, and we have taken your symptoms seriously. The pattern of your pain — how it has spread, how it behaves, and how it has responded to the block — suggests that the primary driver of your pain is now in the central nervous system rather than at the site of the original nerve injury. That is a treatable condition, but the tools that work for it are different from the tools that work for a discrete nerve compression. Another operation on the original site is unlikely to give you the result we both want. What is likely to help is a combined plan that may include targeted medications, a specific type of physical therapy, and a form of pain-focused psychology that has strong evidence in this exact situation." Avoid "your pain is not real," "there is nothing wrong," or any implication that the patient has caused the problem.

5.5 Decision flow by criterion count

6. Limitations and Open Questions

The framework is diagnostic, not prognostic. It identifies patients whose pain is likely centralized; it does not yet predict which intervention among the central-focused options will work best for a given patient. Prospective validation in surgical decision-making cohorts is not yet available. Criterion #5 (<50% block response) depends on the block being technically well-executed; false negatives are possible when the block misses the intended target or when timing of assessment is off. The framework's applicability to compression neuropathies without a discrete injury event — for example, long-standing carpal tunnel syndrome with widespread hypersensitivity — is not fully addressed and represents an important open question. Overlap with CRPS and post-surgical pain phenotypes remains an active area of research, as does the question of how to distinguish partial centralization (where peripheral treatment may still help substantially) from advanced centralization (where it will not). The pediatric population was excluded from the systematic review and no equivalent surgical-population framework exists for children.

7. Case Illustrations

The following are illustrative composites, not real patients. They are provided to demonstrate how the criteria apply in clinical decision-making, not as case reports.

7.1 Case A — Revision decompression candidate, favorable block

A 52-year-old with persistent numbness and shooting pain in the median distribution 18 months after primary carpal tunnel release. Pain is confined to the median territory. No significant mood or sleep component. Diagnostic median nerve block at the distal forearm produces 80% pain relief for the expected duration of the local anesthetic. Criteria met: 1 and 2 (peripheral event, chronicity); not 3 (no extraterritorial spread), not 4 (no significant mood/cognitive component), not 5 (block ≥50%). Interpretation: predominantly peripheral pain; revision decompression is reasonable. Proceed with surgical evaluation and planning.

7.2 Case B — Post-neuroma excision, extraterritorial spread, poor block response

A 34-year-old with persistent burning pain 2 years after saphenous neuroma excision. Pain now involves the entire medial and anterior thigh, with brush allodynia extending well beyond the saphenous territory. Sleep is fragmented; PHQ-9 in the moderate range. Diagnostic saphenous block (ultrasound-guided, confirmed anesthetic effect) produces <30% pain relief. Criteria met: 1, 2, 3, 4, and 5. Interpretation: centralized pain; further peripheral surgery on the saphenous target is unlikely to help durably. Recommend pivot to central-focused care: pain psychology referral, PT for graded desensitization, medication optimization (SNRI first-line), and framing of the diagnosis to the patient.

7.3 Case C — Mixed picture, partial block response

A 46-year-old with persistent pain 14 months after brachial plexus traction injury with partial recovery. Pain is largely within the affected nerve distributions but with modest spread into the adjacent shoulder and scapular region. Significant sleep disturbance and anxiety about return to work. Diagnostic block yields 60% pain relief. Criteria met: 1, 2, 4; partial on 3; block is above the 50% threshold. Interpretation: mixed peripheral-central presentation with meaningful residual peripheral drivers. A combined approach is appropriate: consider a targeted surgical procedure for a well-defined generator if one is identifiable, alongside concurrent behavioral pain intervention, PT, and medication adjustment. Set explicit expectations with the patient that surgery is one component of a broader plan, not a standalone solution.

8. Conclusion

For the first time, the peripheral nerve surgical community has an evidence-derived, surgically operational vocabulary for identifying centralized pain in its own patients. The Raasveld-Eberlin framework does not resolve every diagnostic ambiguity, and it is not a substitute for careful clinical judgment. What it does provide is a shared structure — five criteria, one of which is a physiologic test the surgeon already knows how to interpret — for deciding whether an additional peripheral operation is likely to help, or whether the patient needs a different treatment approach. Appropriate patient selection is the surgeon's most consequential contribution to outcomes in this population; a common language for centralized pain makes that contribution more reliable, more defensible, and more useful to the patient.