Beyond Tissue Damage: How Nociplastic Pain Is Reshaping Pain Medicine

nociplastic pain

Understanding Nociplastic Pain

Chronic pain is no longer understood simply as a direct signal of tissue damage.

In modern pain medicine, we increasingly see patients whose pain intensity, distribution, and disability are far out of proportion to structural findings on imaging. Many of them have undergone multiple injections or even surgeries with little sustained benefit. These “mismatch” cases force us to move beyond a purely damage-centred model towards a mechanism-based understanding of pain. Beyond_Tissue_Damage_Nociplasti…

This article summarises how the concept of nociplastic pain and the Daradia Nociplastic Pain Checklist can help clinicians recognise these patterns, and how the Daradia EXPLAIN–MOVE–CALM protocol offers a pragmatic framework for management. Nociplastic pain-Daradia Protoc…

The Modern Definition of Pain

The International Association for the Study of Pain (IASP) defines pain as:

“An unpleasant sensory and emotional experience associated with, or resembling that associated with, actual or potential tissue damage.” Beyond_Tissue_Damage_Nociplasti…

This definition emphasises that:

  • Pain is always both sensory and emotional.
  • Pain can be present even without ongoing tissue damage.
  • Pain is an experience, shaped by biological, psychological, and social factors.

This shift in definition lays the foundation for understanding neuropathic and nociplastic pain, where ongoing tissue damage may be absent or insufficient to explain the patient’s experience.

Three Mechanistic Types of Pain: Nociceptive, Neuropathic, Nociplastic

Modern pain medicine uses three mechanistic descriptors that often overlap in the same patient:

1. Nociceptive Pain – “Signal from the Tissues”

  • Driven by actual or threatened non-neural tissue damage (inflammation, mechanical overload, trauma).
  • Examples: acute ankle sprain, osteoarthritis flare, acute myofascial strain.
  • Typically localised, mechanical or inflammatory pattern, proportional to tissue load.
  • Usually responds well to rest, NSAIDs, joint protection, and appropriately targeted structural interventions.

2. Neuropathic Pain – “Injury to the Wiring”

  • Definition: Pain caused by a lesion or disease of the somatosensory nervous system.
  • Examples: diabetic neuropathy, post-herpetic neuralgia, radiculopathy, phantom limb pain.
  • Features: burning, electric shocks, shooting pain, paresthesias, sensory loss or gain.
  • Requires evidence of nerve lesion on examination and/or investigations; treatment focuses on the underlying lesion plus neuropathic pain medications.

3. Nociplastic Pain – “Altered Processing”

  • Definition: Pain arising from altered nociception despite no clear evidence of actual or threatened tissue damage activating nociceptors, or of disease or lesion of the somatosensory system, that would explain the degree of pain. Nociplastic pain-Daradia Protoc…
  • Typical presentations: fibromyalgia, chronic widespread musculoskeletal pain, some chronic low back and neck pain.
  • Maintained by central sensitisation and disturbed pain modulation.
  • Often accompanied by sleep disturbance, fatigue, cognitive “fog,” mood symptoms, and sensory hypersensitivity.

In real life, patients often have mixed mechanisms. The key clinical task is to identify the dominant mechanism at a given time, so that treatment can be tailored appropriately.

Clinical Vignettes: When Tissue Damage Does Not Explain the Pain

Case 1: Phantom Limb Pain – Pain from a Missing Limb

A 55-year-old man, one year after above-knee amputation, reports severe burning and crushing pain in his “missing” foot. The stump is well healed, imaging is normal, yet pain is intense and disabling. Beyond_Tissue_Damage_Nociplasti…

  • There is no non-neural tissue in the painful area – the foot no longer exists.
  • There is a clear neural lesion: severed peripheral nerves, dorsal horn reorganisation, cortical remapping.
  • Pain is generated by abnormal activity and reorganisation within the nervous system itself.

This is classic neuropathic pain, and it dramatically challenges the old assumption: “No tissue – no pain.”

Case 2: Fibromyalgia-Like Presentation – Normal Tests, Severe Pain

A 42-year-old woman presents with 3-year history of widespread musculoskeletal pain, fatigue, poor sleep, “brain fog,” and low mood. X-rays, MRI, and labs are repeatedly normal. Multiple injections and analgesics have given only transient benefit.

  • No clear ongoing tissue damage.
  • No definite neuropathic lesion.
  • Pain is widespread and disproportionate to any subtle structural findings.
  • Central symptom cluster is prominent.

This pattern strongly suggests nociplastic pain.

Case 3: Chronic Low Back Pain “Mismatch”

A 60-year-old office worker has chronic low back pain for 5 years, some intermittent leg symptoms, and high disability. MRI shows age-related degenerative changes but no major stenosis or instability. He has undergone multiple injections and even surgery with little lasting relief. Beyond_Tissue_Damage_Nociplasti…

Again, we see a mismatch between structural pathology and the severity and spread of pain. This is a hallmark of nociplastic mechanisms.

Concept and Clinical Features of Nociplastic Pain

Nociplastic pain conceptually lies between “pure” nociceptive and “pure” neuropathic pain, though in practice many patients have overlapping components. Nociplastic pain-Daradia Protoc…

Common Clinical Features

Typical features include: Nociplastic pain-Daradia Protoc…

  • Disproportionate pain relative to observable structural changes.
  • Multifocal or widespread distribution, often crossing joint/dermatomal boundaries.
  • Central symptom cluster:
    • Non-refreshing sleep
    • Daytime fatigue
    • Cognitive difficulties (“brain fog”)
    • Anxiety and/or low mood
    • Sensory hypersensitivity (light, sound, touch)
  • Poor or short-lived response to peripherally targeted treatments (NSAIDs, local injections, surgery).
  • Frequent coexistence of central sensitivity syndromes such as:
    • Fibromyalgia
    • Irritable bowel syndrome
    • Temporomandibular disorder (TMD)
    • Chronic pelvic pain
    • Tension-type headache/migraine
    • Chronic widespread pain

These patterns reflect changes in the pain system rather than ongoing damage in a particular structure.

Mechanisms: Central Sensitisation and Altered Pain Modulation

The best studied mechanism underlying nociplastic pain is central sensitisation – an increased responsiveness of nociceptive neurons in the central nervous system to normal or subthreshold inputs. Nociplastic pain-Daradia Protoc…

Key features of central sensitisation include:

  1. Amplification of Incoming Signals
    • Hyperalgesia: increased pain from a normally painful stimulus.
    • Allodynia: pain from a normally non-painful stimulus.
  2. Expansion of Receptive Fields
    • Neurons respond to inputs from larger body areas.
    • Pain spreads beyond the original site of injury or pathology.
  3. Altered Descending Modulation
    • Reduced descending inhibition and/or increased facilitation from brain to spinal cord.
    • Net result: a nervous system that is “turned up” rather than “balanced.” Nociplastic pain-Daradia Protoc…
  4. Interaction with Psychosocial Factors
    • Stress, poor sleep, mood disturbances, fear-avoidance, and adverse life events can all intensify central sensitisation.

Because central sensitisation is not directly measurable at the bedside, clinicians rely on:

  • Symptom-based tools (e.g., Central Sensitization Inventory in research).
  • Bedside testing for widespread tenderness, mechanical allodynia, and temporal summation (increasing pain with repeated light tapping or pressure, and after-sensations). Nociplastic pain-Daradia Protoc…

Why Pain Physicians Must Actively Look for Nociplastic Pain

Failing to recognise nociplastic mechanisms in chronic pain has real consequences. Nociplastic pain-Daradia Protoc…

1. Avoiding Low-Value and Harmful Interventions

If nociplastic-dominant pain is mislabelled as purely nociceptive or neuropathic, patients often undergo:

  • Repeated injections and blocks
  • Escalating NSAIDs or opioids
  • Multiple surgeries

with minimal or short-lived benefit. Identifying a nociplastic pattern early allows clinicians to limit such low-value interventions.

2. Guiding Mechanism-Based Multimodal Care

Nociplastic pain responds best to:

  • Pain neuroscience education
  • Graded activity and exercise
  • Cognitive-behavioural and other psychological interventions
  • Carefully chosen centrally acting medications

These are underused when clinicians keep searching for a structural cause.

3. Improving Communication and Reducing Stigma

Giving patients a clear, respectful explanation – “Your pain is real, and your pain system has become sensitised” – helps move away from phrases like “nothing is wrong” or “it is all in your head.” Nociplastic pain-Daradia Protoc…

4. Supporting Documentation, Research, and Quality Improvement

Mechanistic labels (nociceptive, neuropathic, nociplastic) improve:

  • Documentation in records
  • Risk stratification
  • Research on which phenotypes respond to which treatments

The Daradia Nociplastic Pain Checklist: 10 Clinical Items with a 3/7 Rule

To bridge the gap between concepts and daily practice, Daradia developed a 10-item Nociplastic Pain Checklist specifically designed for busy pain clinics and interventional practice.

Prerequisites for Using the Checklist

Use the checklist only after:

  • Screening for red flags (infection, fracture, malignancy, progressive neurological deficit, active inflammatory disease).
  • Adequate evaluation for nociceptive sources (e.g., fracture, inflammatory arthritis, clear mechanical overload).
  • Assessment for neuropathic lesions (radiculopathy, peripheral neuropathy, CRPS type 2, etc.).

Nociplastic pain should be a positive diagnosis, not a default “diagnosis of exclusion.”

The 10 Items (Yes/No)

  1. Chronicity with Poor Structural Explanation
    Pain ≥ 3 months with no structural lesion that fully explains severity and spread.
  2. Disproportionate Pain/Disability
    Pain intensity and/or disability clearly disproportionate to imaging and examination.
  3. Widespread or Shifting Distribution
    Pain is multifocal, widespread, or shifting over time rather than confined to a single joint or dermatome.
  4. Generalised Hyperalgesia or Allodynia
    Widespread pressure tenderness or mechanical allodynia beyond the primary region.
  5. Central Symptom Cluster
    At least two of: non-refreshing sleep, fatigue, cognitive “fog,” anxiety/depression, sensory hypersensitivity.
  6. History of Central Sensitivity Syndromes
    Fibromyalgia, IBS, chronic pelvic pain, TMD, chronic tension-type headache, chronic widespread pain, etc.
  7. Limited or Short-Lived Response to Peripheral Treatments
    Inadequate or transient benefit from NSAIDs, local injections, or surgery despite adequate technique.
  8. Temporal Summation/After-Sensations
    Repeated light tapping or pressure produces a clear increase in pain or prolonged pain after the stimulus.
  9. Absence of a Clear Neuropathic Lesion
    No somatosensory lesion sufficient to explain a neuropathic-dominant pattern.
  10. Absence of a Clearly Dominant Nociceptive Driver
    No single major nociceptive driver (e.g., fracture, active inflammatory arthritis) that explains the whole picture. Nociplastic pain-Daradia Protoc…

The “3/7 Rule” for Interpretation

Let N = number of “Yes” answers (0–10).

  • N < 3 – Nociplastic pain unlikely
    Nociceptive or neuropathic mechanisms are more likely dominant. Treat these first and monitor.
  • N ≥ 3 – Suspected nociplastic contribution
    Start basic education and graded activity; be cautious with repeated purely structural interventions.
  • N ≥ 7 – Nociplastic-dominant pain (Daradia classification)
    No single nociceptive or neuropathic lesion fully explains the clinical picture.
    Example documentation: “Chronic low back pain with nociplastic-dominant mechanism (Daradia checklist 8/10).”

Applying the Daradia Checklist: Examples

Fibromyalgia-Type Case

  • Chronicity with mismatch: Yes
  • Widespread shifting pain: Yes
  • Central symptom cluster: Yes
  • Widespread tenderness and temporal summation: Yes
  • Poor response to structural treatments: Yes
  • No major nociceptive or neuropathic driver: Yes

Typical N ≥ 7 → nociplastic-dominant pain → start the Daradia EXPLAIN–MOVE–CALM protocol.

Chronic Low Back Pain “Mismatch”

  • Chronic pain with only mild-to-moderate degenerative changes: Yes
  • Pain/disability disproportionate to imaging: Yes
  • Some spread beyond the low back (buttocks, thighs, sometimes upper back): often Yes
  • Sleep and mood issues: often Yes
  • Multiple injections/surgeries with limited durability: Yes

If N ≥ 7 and no strong alternative driver, treat as nociplastic-dominant, rather than repeating structural procedures.

The Daradia Protocol for Nociplastic-Dominant Pain: EXPLAIN–MOVE–CALM

Once nociplastic-dominant pain is identified (N ≥ 7), management at Daradia is organised into three pillars:

  1. EXPLAIN – Pain Neuroscience Education
  2. MOVE – Graded Activity and Exercise
  3. CALM – Sleep, Mood, Stress and Rational Pharmacotherapy

Pillar 1: EXPLAIN

Goals:

  • Provide a clear, non-stigmatising explanation that the pain is real but driven by a sensitised pain system rather than ongoing damage.
  • Emphasise that nervous system sensitivity is modifiable and reversible.

Practical points:

  • Use metaphors such as a “volume knob,” “sensitive car alarm,” or “over-protective security guard”.
  • Explain why investigations appear “normal” – they look for damage, not for sensitivity.
  • Use diagrams, written material, and involve family members.

Pillar 2: MOVE

Goals:

  • Restore confidence in movement and reverse de-conditioning.

Practical points:

  • Prescribe graded, enjoyable activities: walking, cycling, swimming, yoga, stretching, light strengthening.
  • Start below the flare-up threshold and progress slowly and consistently.
  • Teach pacing to avoid boom-and-bust cycles.
  • Use selected interventions (e.g., a single targeted injection) only to facilitate rehabilitation, not as repeated stand-alone “fixes.”
  • Track progress by function and participation, not only by pain scores.

Pillar 3: CALM

Goals:

  • Optimise sleep, mood, and stress to turn down the global threat and arousal signals feeding the pain system.

Practical points:

  • Address sleep with behavioural strategies; consider short-term pharmacological support if necessary.
  • Screen for anxiety, depression, PTSD; refer for CBT, ACT, or mindfulness-based therapies where available.
  • Use centrally acting medications (e.g., low-dose TCAs or SNRIs) when indicated.
  • Be cautious with gabapentinoids; avoid long-term high-dose opioids and escalating NSAIDs in clear nociplastic-dominant pain.
  • Integrate relaxation, breathing exercises, and stress-management into the care plan. Nociplastic pain-Daradia Protoc…

A Nociplastic-Dominant Patient Journey at Daradia

A typical pathway may look like this:

  1. Recognise the pattern and complete the Daradia checklist.
  2. Explain the mechanism and reframe the problem with the patient.
  3. Co-create an EXPLAIN–MOVE–CALM plan, with specific, realistic goals.
  4. Review regularly, celebrating small gains in function and quality of life, not just pain scores.
  5. Adjust the plan as mechanisms evolve; combine with targeted structural treatments if a new nociceptive or neuropathic driver appears.

Future Directions

The Daradia checklist and protocol are pragmatic clinical tools derived from contemporary literature and specialist experience. Formal validation is the next step. Priority research areas include: Nociplastic pain-Daradia Protoc…

  • Prospective validation of the 3/7 rule against IASP nociplastic criteria and expert consensus.
  • Inter-rater reliability across different clinicians and settings.
  • Treatment-response studies comparing nociplastic-dominant vs non-nociplastic phenotypes.
  • Cross-cultural adaptations for different healthcare environments, including low- and middle-income countries.

Key Take-Home Messages for Clinicians

  • Not all pain equals ongoing tissue damage. Phantom limb pain and fibromyalgia clearly illustrate this.
  • Nociplastic pain is common, under-recognised, and central to many complex chronic musculoskeletal cases.
  • The Daradia Nociplastic Pain Checklist (10 items, 3/7 rule) offers a clinic-friendly way to identify nociplastic and nociplastic-dominant pain.
  • The EXPLAIN–MOVE–CALM protocol provides a simple, mechanism-based framework for management.
  • By focusing on mechanisms rather than only on structures, pain physicians can reduce low-value interventions and offer more effective, compassionate care.

References

  1. Fitzcharles MA, Cohen SP, Clauw DJ, Littlejohn G, Usui C, Häuser W. Nociplastic pain: towards an understanding of prevalent pain conditions. Lancet. 2021;397(10289):2098-2110.
  2. Kosek E, Clauw D, Nijs J, et al. Chronic nociplastic pain affecting the musculoskeletal system: clinical criteria and grading system. Pain. 2021;162(11):2629-2634.
  3. Cho JH. Nociplastic pain. Ann Clin Neurophysiol. 2023;25(2):78-83.
  4. Yoo YM, Kim KH. Current understanding of nociplastic pain. Korean J Pain. 2024;37(2):107-118.
  5. Nijs J, Lahousse A, Kapreli E, et al. Nociplastic Pain Criteria or Recognition of Central Sensitization? Pain Phenotyping in the Past, Present and Future. J Clin Med. 2021;10(15):3203.
  6. Nijs J, George SZ, Clauw DJ, et al. Central sensitisation in chronic pain conditions: latest discoveries and their potential for precision medicine. Lancet Rheumatol. 2021;3(5):e383-e392.
  7. van Griensven H, Schmid A, Trendafilova T, Low M. Central Sensitization in Musculoskeletal Pain: Lost in Translation? J Orthop Sports Phys Ther. 2020;50(11):592-596.
  8. Neblett R, Hartzell MM, Cohen H, et al. Ability of the Central Sensitization Inventory to identify central sensitivity syndromes in an outpatient chronic pain sample. Clin J Pain. 2015;31(4):323-332.
  9. Bilika P, Nijs J, Billis E, et al. Applying Nociplastic Pain Criteria in Chronic Musculoskeletal Conditions: A Vignette Study. J Clin Med. 2025;14(4):1179.
  10. Kim KH. Nociplastic pain: conceptual and terminological considerations. Korean J Pain. 2025;38(2):87-88.

https://www.slideshare.net/slideshow/beyond-tissue-damage-how-nociplastic-pain-is-reshaping-our-understanding-of-pain/284496478

Frequently Asked Questions (FAQs) – Nociplastic Pain & Daradia Protocol

1. What is nociplastic pain?

Nociplastic pain is a type of chronic pain caused by altered pain processing in the nervous system, without clear tissue damage or nerve injury. The brain and spinal cord become overly sensitive to pain signals.

2. How is nociplastic pain different from neuropathic pain?

Neuropathic pain is caused by actual damage to nerves, while nociplastic pain occurs due to dysfunction in pain modulation pathways. In nociplastic pain, routine scans and nerve tests are often normal.

3. What are common conditions associated with nociplastic pain?

Common nociplastic pain conditions include:

  • Fibromyalgia
  • Chronic widespread pain
  • Chronic low back pain without structural cause
  • Chronic neck pain
  • Tension-type headache
  • Some cases of migraine and pelvic pain

4. Why do scans and MRI appear normal in nociplastic pain?

Because nociplastic pain does not arise from structural tissue damage or nerve compression, imaging studies like MRI or X-ray often do not show abnormalities. Pain originates from central nervous system sensitization.

5. Is nociplastic pain a “psychological” pain?

No. Nociplastic pain is a real biological pain condition involving abnormal pain processing in the brain and spinal cord. Psychological factors may influence pain severity but are not the cause of the condition.

6. What is central sensitization?

Central sensitization is a condition where the nervous system becomes hyper-responsive, amplifying pain signals. Even mild stimuli or normal body sensations can be perceived as painful.

7. How is nociplastic pain diagnosed?

Diagnosis is clinical and based on:

  • Detailed history
  • Pain pattern and distribution
  • Absence of clear structural pathology
  • Associated symptoms like fatigue, poor sleep, and cognitive difficulty

There is no single blood test or scan to confirm nociplastic pain.

8. What is the Daradia Protocol for nociplastic pain?

The Daradia Protocol is a structured, stepwise, multidisciplinary approach designed specifically for nociplastic pain, focusing on nervous system modulation rather than tissue-based treatment alone.

9. What are the key components of the Daradia Protocol?

The Daradia Protocol includes:

  • Patient education and pain neuroscience explanation
  • Rational pharmacotherapy targeting central pain modulation
  • Physical rehabilitation and graded activity
  • Sleep and lifestyle optimization
  • Psychological and behavioral strategies when required

10. Why do conventional painkillers often fail in nociplastic pain?

Conventional painkillers target inflammation or tissue injury. Since nociplastic pain arises from abnormal pain processing, these medicines are often ineffective or provide minimal relief.

11. Can interventional pain procedures help nociplastic pain?

Interventional procedures have a limited role in pure nociplastic pain. They may be helpful only when there is an associated nociceptive or neuropathic component. The primary focus remains central pain modulation.

12. Is nociplastic pain treatable?

Yes. Although nociplastic pain is chronic, symptoms can be significantly reduced and quality of life improved with a structured, long-term, multidisciplinary treatment approach like the Daradia Protocol.

13. How long does treatment take to show improvement?

Improvement is gradual and varies between individuals. Many patients notice meaningful improvement over weeks to months with consistent adherence to the treatment plan.

14. Can nociplastic pain worsen if untreated?

Yes. Untreated nociplastic pain can lead to further central sensitization, disability, sleep disturbances, emotional distress, and reduced quality of life.

15. Who should consult a pain specialist for nociplastic pain?

Patients with:

  • Long-standing pain without clear cause
  • Multiple pain sites
  • Poor response to routine treatments
  • Associated fatigue, sleep problems, or mood changes

should consult a pain physician experienced in nociplastic pain management.

16. Is long-term medication always required?

Not always. Medications may be needed initially, but the goal of the Daradia Protocol is functional improvement, nervous system retraining, and gradual reduction of medicine dependence whenever possible.

17. Can lifestyle changes really help nociplastic pain?

Yes. Sleep regulation, physical activity, stress reduction, and regular routines play a critical role in normalizing pain processing pathways and improving outcomes.

18. Is nociplastic pain recognized internationally?

Yes. Nociplastic pain is formally recognized by the International Association for the Study of Pain (IASP) as a distinct pain mechanism, separate from nociceptive and neuropathic pain.