Blue Portance Expert Guides

Understanding Pain

The biological, mechanical, and neurophysiological mechanisms that explain how sitting-related pain develops and why it persists.

This article is part of the Expert Guide “Understanding Pain”.

Nociceptive, Neuropathic, and Nociplastic Pain: Three Mechanisms That Can Combine

Epistemic note — This article belongs to the “Understanding Pain” Expert Guide of the Blue Portance Knowledge Base: the concepts defined here form the foundation used throughout the Expert Guides, frequently asked questions, lived experiences, and case studies. It also distinguishes between knowledge established in the scientific literature, the biomechanical model proposed by Blue Portance, and hypotheses or clinical observations that are not yet the subject of an established consensus. Finally, it aims to explain general mechanisms and does not constitute a medical diagnosis or prescription.

Pain can arise from three main mechanisms: the activation of nociceptors by an actual or potential threat to tissues (nociceptive mechanism), a lesion or disease of the somatosensory nervous system (neuropathic mechanism), or altered nociception that cannot be sufficiently explained by the two previous mechanisms (nociplastic mechanism). These mechanisms are not three sealed boxes: they can coexist, change over time, and contribute in different proportions to the same pain experience.

Why this article matters

The foundational article “Why Do I Hurt?” described the general chain linking a mechanical stress, a tissue, nociceptionNociceptionNociception is the process by which the nervous system detects and encodes stimuli that are potentially damaging to tissues. It is not the same as pain, which is an experience.Read the full entry : Nociception, nerve transmission, brain integration, and the pain experience. This chain explains how a signal can arise and why pain can never be reduced to a simple snapshot of a lesion.

One essential question remains, however: which mechanism is mainly driving this experience? The signal may come from tissues under threat, from the somatosensory system itself when it is injured or diseased, or from profoundly altered nociception without sufficient evidence of either of these mechanisms. These distinctions now structure the international terminology of pain (IASP; Raja et al., 2020), and they are also part of the chronic painChronic painPain is called chronic when it persists or recurs for more than three months. It may accompany an identified disease or be a condition in its own right.Read the full entry : Chronic pain classification proposed by the IASP for the 11th revision of the International Classification of Diseases (Treede et al., 2019).

On their own, they are not enough to make a diagnosis. They do, however, provide an essential framework for avoiding several errors: believing that intense pain necessarily proves significant damage, labeling as neuropathic any pain felt along the course of a nerve, or reducing nociplastic painNociplastic painNociplastic pain is pain arising from altered nociception, without clear evidence of tissue damage activating nociceptors, or of a lesion or disease of the somatosensory system sufficient to explain the pain.Read the full entry : Nociplastic pain to “psychological” pain.

Three different questions

Nociceptive: are nociceptors being activated by an actual or potential threat to non-neural tissues?
Neuropathic: is there a lesion or disease of the somatosensory nervous system that could explain the distribution and the signs observed?
Nociplastic: does nociception appear altered, without peripheral nociceptive activation or somatosensory involvement being sufficient to explain the pain?

1. Three mechanisms, not three levels of pain intensity

The terms nociceptive, neuropathic, and nociplastic do not describe how intense a pain is. Nociceptive painNociceptive painNociceptive pain is pain related to actual or threatened damage to non-neural tissue, resulting from the activation of nociceptors. The somatosensory nervous system is functioning normally.Read the full entry : Nociceptive pain can be extremely intense; neuropathic painNeuropathic painNeuropathic pain is pain caused by a lesion or disease of the somatosensory nervous system.Read the full entry : Neuropathic pain can remain intermittent; nociplastic pain can be localized or widespread. In reality, these terms primarily describe the biological mechanism considered to explain the pain.

The IASP also points out that pain and nociception are two distinct phenomena: the activity of sensory neurons alone is not enough to demonstrate or measure what a person actually experiences (IASP Terminology; Raja et al., 2020). All pain is therefore integrated by the central nervous system, but not all pain originates in the same process.

The three biological mechanisms of pain: nociceptive, neuropathic, and nociplastic. — Figure 1 — The 3 mechanisms of pain The nociceptive, neuropathic, and nociplastic mechanisms correspond to three distinct biological processes that can contribute, alone or in combination, to the same pain.

2. The nociceptive mechanism: when a threat to tissue activates nociceptors

IASP terminology

Nociceptive pain is associated with actual or potential damage to non-neural tissue and results from the activation of nociceptors. This definition, by contrast, distinguishes it from neuropathic pain, which implies a lesion or disease of the somatosensory system.

Nociceptors are specialized sensory endings capable of transducing potentially threatening mechanical, thermal, or chemical stimuli. Their activation then produces signals transmitted to the spinal cord and supraspinal structures, where they are modulated and integrated (Basbaum et al., 2009; Julius, 2013).

In sitting-related pain, the stimulus is often mechanical: compression, traction, shearShearShear is a deformation produced by forces parallel or tangential to a surface, which cause neighboring layers or regions of a tissue to slide relative to one another.Read the full entry : Shear, friction, sustained deformation, or repeated stress. It may also involve a joint capsule, a ligament, an enthesis, a muscle, a tendon, fasciaFasciaFascia are connective tissue structures that envelop, connect or separate certain parts of the body. The "fascial system" refers to a broader set of connective tissues considered in their functional continuity.Read the full entry : Fascia, the periosteum, or other innervated tissues. Local inflammation or ischemia can then sensitize nociceptors and lower their response threshold (Basbaum et al., 2009; Gold & Gebhart, 2010).

Diagram showing the nociceptive mechanism from mechanical stress and tissue loading to nociceptor activation, neural transmission, and pain perception. — Figure 2 — Nociceptive pain: how does it work? When a mechanical stress exceeds a tissue’s adaptive capacity, it can activate nociceptors. The signal is then transmitted to the spinal cord and brain, where it is modulated and integrated before pain is perceived.

Nociception does not mean visible damage

The term nociceptive does not necessarily mean that a tear, a fracture, or an imaging abnormality must be visible. A potential threat, local inflammation, sustained deformation, or a functional disturbance can activate or sensitize nociceptors without producing a detectable macroscopic lesion. Conversely, a visible anatomical abnormality may remain painless.

This is where the notion of tissue adaptive capacity, developed in the foundational article, comes in: the effect of a mechanical stress depends on its intensity, but also on its duration, its repetition, the recovery available, and the condition of the tissue receiving it. This formulation is a biomechanical way of organizing the problem. It does not, however, replace the international definition of the nociceptive mechanism.

3. The neuropathic mechanism: when the somatosensory system is affected

Reference clinical definition

Neuropathic pain is pain caused by a lesion or disease of the somatosensory nervous system (Finnerup et al., 2016; IASP).

This definition sets an important requirement: pain felt in a nerve’s distribution, pain described as burning, or pain triggered by a posture is not, on its own, proof of a neuropathic mechanism. In practice, one must look for a compatible history, an anatomically plausible distribution, and positive or negative signs suggesting somatosensory involvement (Finnerup et al., 2016).

When a nerve is injured or diseased, several phenomena can contribute to pain: ectopic discharges in sensory fibers or ganglia, changes in ion channel expression, abnormal activity at the lesion site, reorganization of spinal connections, and a reduction in certain inhibitory controls (Baron et al., 2010; Finnerup, Kuner & Jensen, 2021). In concrete terms, an ectopic discharge is an electrical signal fired spontaneously by an injured nerve fiber — a bit like a stripped wire giving off sparks without any external stress being applied.

Why nerve compression does not automatically mean “neuropathic pain”

A peripheral nerve is not just a cable made of axons. It includes connective sheaths, blood vessels, and a mechanical environment. Compression or tensioning may first load the sheaths and neighboring tissues, alter blood supply, or disrupt gliding. These elements can generate a nociceptive component. A neuropathic component, for its part, appears when the mechanical stress is associated with a lesion or disease of the somatosensory system that meets the accepted definition.

The two mechanisms can therefore coexist. This coexistence explains why it would be simplistic to contrast an entirely nociceptive “irritated nerve” with an entirely neuropathic “injured nerve” as two states that are always easy to tell apart.

Diagram showing neuropathic pain arising from a lesion or disease of the somatosensory nervous system and its possible coexistence with nociceptive pain. — Figure 3 — Neuropathic pain: how does it work? Neuropathic pain implies a lesion or disease of the somatosensory nervous system. A nociceptive component may nevertheless coexist when the nerve’s sheaths, its blood vessels, or the surrounding tissues are also under load.

4. The nociplastic mechanism: when nociception is altered

IASP terminology

Nociplastic pain arises from altered nociception, without clear evidence of actual or potential damage to non-neural tissue activating nociceptors, or of a lesion or disease of the somatosensory system explaining the pain.

The term nociplastic was introduced to address a persistent difficulty: some pain could not be adequately classified as nociceptive or neuropathic, even though the pain experience, the functional limitations, and the changes in sensitivity were real. The term was proposed in the IASP taxonomy in 2016–2017, and clinical criteria were subsequently developed for certain chronic musculoskeletal pain conditions (Kosek et al., 2016; Kosek et al., 2021).

Nociplastic pain should not be summed up as “the brain inventing pain.” On the one hand, pain is always an experience produced by the nervous system; on the other, the expression altered nociception does not refer exclusively to a brain phenomenon. It may involve changes in information processing at several levels of the nociceptive system. Central sensitizationCentral sensitizationCentral sensitization refers to an amplification of the central nervous system's response to sensory signals: pain can then be more intense, more widespread or longer-lasting than the state of the tissues would suggest.Read the full entry : Central sensitization is an important mechanism, but it is not a perfect synonym for nociplastic pain (Woolf, 2011; Fitzcharles et al., 2021; Nijs et al., 2023).

Diagram showing altered nociception, increased nervous system sensitivity, signal amplification, and nociplastic pain. — Figure 4 — Nociplastic pain: how does it work? Nociplastic pain corresponds to altered nociception that is not sufficiently explained by peripheral nociceptive activation or by a lesion of the somatosensory system. It may also be accompanied by amplification, spreading, or insufficient modulation of pain-related information.

A useful category, but not a diagnosis by default

Normal imaging or the absence of an obvious lesion is not enough to conclude that a mechanism is nociplastic. Instead, the proposed criteria rely on a set of clues: chronicity, regional or multifocal distribution, hypersensitivity, associated symptoms, and the inability of nociceptive or neuropathic mechanisms to explain the overall clinical picture (Kosek et al., 2021).

Some conditions, such as fibromyalgiaFibromyalgiaFibromyalgia is a chronic pain syndrome combining persistent widespread pain, fatigue, sleep disturbances and often difficulty concentrating, with no tissue damage that could on its own explain the intensity of the symptoms.Read the full entry : Fibromyalgia, are models frequently associated with this mechanism. Other situations may show a variable nociplastic component, in combination with inflammation, tissue damage, or neuropathy. The mechanism should therefore not be confused with the name of a disease.

5. Why can’t symptoms alone classify pain?

Verbal descriptions are valuable, but they are not specific. Burning can occur in neuropathic pain, but also with skin inflammation or tissue irritation. Diffuse pain may suggest a nociplastic component, but it can also result from several peripheral pain generators or from referred pain. Finally, allodyniaAllodyniaAllodynia is pain caused by a stimulus that is normally not painful: a light touch, the contact of clothing, gentle pressure. It is a descriptive clinical term: it describes what the person feels, without by itself designating a mechanism.Read the full entry : Allodynia can accompany different forms of sensitization.

That is why clinical classification systems combine several dimensions: pain history, location, anatomical distribution, triggering factors, sensory examination, available objective findings, and the overall consistency of the presumed mechanism (Finnerup et al., 2016; Kosek et al., 2021).

Question	Nociceptive mechanism	Neuropathic mechanism	Nociplastic mechanism
Core process	Activation of nociceptors by an actual or potential threat to non-neural tissues.	Lesion or disease of the somatosensory nervous system.	Altered nociception not sufficiently explained by peripheral nociceptive activation or somatosensory involvement.
Possible clues	Notably, a reproducible link with a load, pressure, movement, inflammation, or a plausible tissue area.	In particular, a neuroanatomically plausible distribution, positive or negative sensory symptoms, or signs compatible with somatosensory involvement.	More widespread hypersensitivity, disproportion or variability, associated symptoms, nociceptive and neuropathic mechanisms insufficient to explain the overall picture.
What is not enough	Pain that is localized or provoked by movement.	Burning, radiating pain, or the anatomical proximity of a nerve.	Normal imaging, how long the pain has lasted, or the presence of psychological stress.
Overlap	All three mechanisms can contribute simultaneously to the same pain situation.

6. Can the mechanisms combine?

Yes. Publications on pain mechanisms emphasize that the categories are useful for reasoning, but that real-world clinical presentations are often mixed (Fitzcharles et al., 2021; Finnerup, Kuner & Jensen, 2021).

Diagram showing that nociceptive, neuropathic, and nociplastic mechanisms can coexist and contribute in different proportions to the same pain. — Figure 5 — The 3 mechanisms are not separate boxes The same pain can involve several biological mechanisms. Their relative contribution may therefore vary depending on the person, the context, and the stage of its course.

Osteoarthritis may combine nociceptive activation from joint tissues with more widespread changes in sensitivity. Likewise, radiculopathy may bring together a nociceptive component arising from spinal structures and a neuropathic component related to nerve root involvement. Finally, chronic pelvic pain may combine tissue stress, documented nerve involvement, and progressively altered nociception.

The example of pudendal neuralgia

Pain felt in the pudendal distribution illustrates particularly well the need to distinguish between levels. Pressure or traction in the pelvic region can load muscles, ligaments, fascia, the nerve’s sheaths, and its blood vessels: these structures may contribute to a nociceptive component. If a lesion or disease of the somatosensory system is established, a neuropathic component may be considered. If the pain persists with hypersensitivity that goes beyond what these mechanisms explain, a nociplastic component may also be discussed.

This interpretation does not mean that every case of pudendal neuralgiaPudendal neuralgiaNeuropathic pain in the territory of the pudendal nerve (perineum, external genitalia, anal region), often made worse by sitting.Read the full entry : Pudendal neuralgia necessarily follows this sequence. It simply shows that the same clinical diagnosis can encompass different mechanistic contributions, which partly explains the diversity of experiences and of reactions to sitting.

7. Can pain evolve over time?

The three mechanisms are not three fixed compartments: in certain documented situations, prolonged mechanical stress can, step by step, shift the respective contribution of each mechanism. For example, persistent nociception can promote peripheral sensitizationPeripheral sensitizationPeripheral sensitization is increased responsiveness and reduced threshold of peripheral nociceptive neurons to the stimulation of their receptive fields (IASP definition).Read the full entry : Peripheral sensitization of nociceptors; if the nerve structure itself eventually becomes affected, a neuropathic component may appear; prolonged central sensitization may, in some cases, contribute to the development of a nociplastic component (Woolf, 2011; Latremoliere & Woolf, 2009).

Diagram showing a possible evolution from repeated mechanical stress to persistent nociception, nerve involvement, sensitization, and a nociplastic component. — Figure 6 — Pain can evolve: a dynamic continuum In some situations, the contribution of each mechanism may change over time. This trajectory is, however, neither systematic nor linear: each stage may be absent, stabilized, or partially reversible.

This dynamic reading complements, without replacing, the classification by dominant mechanism presented above: it explains why the same pain can be described differently depending on the point in its course, and why the rest of this guide devotes separate articles to each of these mechanisms.

Current controversies and limitations

The boundaries between mechanisms remain imperfect. There is no single biomarker that can automatically assign a pain to a category. Clinical criteria therefore provide levels of probability and must be interpreted in context.

The presence of peripheral nociception is difficult to measure directly in a person.
Likewise, small fiber involvement may go undetected by standard neurophysiological testing.
Central sensitization can accompany nociceptive or neuropathic pain without being sufficient to reclassify it as nociplastic.
In addition, the exact status of certain conditions varies from person to person and depending on the stage of their course.
Finally, biological, psychological, and social mechanisms interact, without this interaction invalidating the mechanistic distinction.

These limitations justify cautious wording: one often speaks of a dominant mechanism, a component, or a probability, rather than absolute and definitive membership in a category.

8. The interpretation proposed by the Blue Portance biomechanical model

The international classification mainly answers the question: which mechanism explains the pain? The Blue Portance biomechanical model, for its part, proposes adding a second question: how have mechanical stresses, tissues, and the nervous system interacted over time to produce the current situation?

This interpretation builds on the chain presented in Figure 1 of the article “Why Do I Hurt?”:

mechanical stress → tissue and adaptive capacity → nociceptive activity or nerve disturbance → transmission and modulation → integration → pain → behavior → adaptation.

From this perspective, the three mechanisms are not treated as three fixed identities, but as three possible modes of contribution:

Nociceptive contribution: mechanical stresses load tissues and activate their nociceptors.
Neuropathic contribution: the somatosensory system is itself injured or diseased and produces pathological activity.
Nociplastic contribution: nociception is persistently altered in a way that the two previous mechanisms can no longer sufficiently explain.

Persistent nociceptive pain does not automatically lead to neuropathy, and neuropathy does not automatically lead to nociplastic pain. However, sustained stimulation can promote sensitization phenomena, and several mechanisms may end up intertwined. The trajectory should therefore be studied as a conditional possibility, never as a universal sequence.

In short, the aim is less to create a new classification than to connect the existing classification to three dimensions that are often considered separately: the nature of the mechanical stress, the adaptive capacity of the structures, and time course.

9. Practical implications for understanding pain

Identifying a mechanism is not the same as assigning a definitive label. It is a way of organizing the questions.

A nociceptive hypothesis leads to asking which tissues are being loaded, by what mechanical stress, for how long, and with what possibility of recovery and variation.
A neuropathic hypothesis likewise leads to looking for somatosensory system involvement, a neuroanatomically consistent distribution, and changes in sensory function.
A nociplastic hypothesis leads to examining whether nociception appears altered beyond what the identified tissue or nerve damage explains, without drawing conclusions from the mere absence of a visible abnormality.
A mixed hypothesis helps prevent one real mechanism from masking the others: a visible lesion does not necessarily explain all the pain, but sensitization does not cancel out the existence of a peripheral mechanical stress either.

This method also helps interpret time course. Pain that appears immediately on contact, pain that gradually increases with sitting time, pain accompanied by sensory deficits, and pain that has become diffuse or unpredictable do not tell the same story. None of these profiles is enough on its own to establish a mechanism, but each one guides the investigation.

Key takeaways

The terms nociceptive, neuropathic, and nociplastic describe mechanisms, not levels of intensity.
Nociceptive pain involves the activation of nociceptors by an actual or potential threat to non-neural tissues.
Neuropathic pain, likewise, implies a lesion or disease of the somatosensory nervous system.
Nociplastic pain corresponds to altered nociception that is not sufficiently explained by the two previous mechanisms.
Burning, radiating pain, or normal imaging are not enough to classify a pain.
In addition, the mechanisms can coexist and their relative contribution may change over time, without following a mandatory sequence.
Finally, the Blue Portance model proposes connecting these mechanisms to the nature of mechanical stresses, adaptive capacity, and time course.

Frequently asked questions

Can pain be both nociceptive and neuropathic?

Yes. A mechanical stress applied near a nerve can activate the nociceptors of its sheaths, its blood vessels, or the surrounding tissues, while involvement of the somatosensory nervous system can simultaneously produce a neuropathic component.

Does a burning sensation prove neuropathic pain?

No. The quality of the sensation is a clue, but it is not specific. Burning can also accompany inflammation or tissue irritation. The anatomical distribution, sensory examination, and clinical history must be taken into account.

Does nociplastic pain mean the pain is psychological?

No. The term describes altered nociception that is not sufficiently explained by peripheral nociceptive activation or by a lesion of the somatosensory system. Psychological and social factors can modulate any pain, but they do not make the experience imaginary.

Does a normal MRI mean the pain is nociplastic?

No. Imaging does not show every functional, tissue, or nerve phenomenon. For this reason, nociplastic pain is not a category assigned automatically when routine diagnostic testing is normal.

Are the three mechanisms three successive stages?

No. They may follow one another in some cases, but this progression is neither mandatory nor universal. Pain may remain mainly nociceptive, be neuropathic from the outset, present a nociplastic component, or combine several mechanisms.

Trying to understand what keeps your sitting-related pain going?

Analyzing pain does not rest solely on its name or location, but on the mechanical stresses, the time course, the structures involved, and the mechanisms that may combine.

Analyze my situation →

Note: this content explains general mechanisms of pain. It therefore cannot determine remotely the mechanism of an individual’s pain and does not replace the advice of a healthcare professional.

Scientific references

Terminology and classification

International Association for the Study of Pain (IASP). IASP Terminology — Pain Definition. 2020. Official terminology.
Raja SN, Carr DB, Cohen M, et al. The revised International Association for the Study of Pain definition of pain: concepts, challenges and compromises. Pain. 2020;161(9):1976–1982. doi:10.1097/j.pain.0000000000001939.
Treede RD, Rief W, Barke A, et al. Chronic pain as a symptom or a disease: the IASP Classification of Chronic Pain for the International Classification of Diseases (ICD-11). Pain. 2019;160(1):19–27.

Nociceptive and neuropathic mechanisms

Basbaum AI, Bautista DM, Scherrer G, Julius D. Cellular and molecular mechanisms of pain. Cell. 2009;139(2):267–284. doi:10.1016/j.cell.2009.09.028.
Julius D. TRP channels and pain. Annual Review of Cell and Developmental Biology. 2013;29:355–384.
Gold MS, Gebhart GF. Nociceptor sensitization in pain pathogenesis. Nature Medicine. 2010;16(11):1248–1257.
Finnerup NB, Haroutounian S, Kamerman P, et al. Neuropathic pain: an updated grading system for research and clinical practice. Pain. 2016;157(8):1599–1606. doi:10.1097/j.pain.0000000000000492.
Baron R, Binder A, Wasner G. Neuropathic pain: diagnosis, pathophysiological mechanisms, and treatment. Lancet Neurology. 2010;9(8):807–819.
Finnerup NB, Kuner R, Jensen TS. Neuropathic pain: from mechanisms to treatment. Physiological Reviews. 2021;101(1):259–301. doi:10.1152/physrev.00045.2019.

Nociplastic mechanism and central sensitization

Kosek E, Cohen M, Baron R, et al. Do we need a third mechanistic descriptor for chronic pain states? Pain. 2016;157(7):1382–1386.
Kosek E, Cohen M, Baron R, et al. Chronic nociplastic pain affecting the musculoskeletal system: clinical criteria and grading system. Pain. 2021;162(11):2629–2634. doi:10.1097/j.pain.0000000000002324.
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. doi:10.1016/S0140-6736(21)00392-5.
Woolf CJ. Central sensitization: implications for the diagnosis and treatment of pain. Pain. 2011;152(3 Suppl):S2–S15. doi:10.1016/j.pain.2010.09.030.
Latremoliere A, Woolf CJ. Central sensitization: a generator of pain hypersensitivity by central neural plasticity. Journal of Pain. 2009;10(9):895–926.
Nijs J, Malfliet A, Nishigami T. Nociplastic pain and central sensitization in patients with chronic pain conditions: a terminology update for clinicians. Brazilian Journal of Physical Therapy. 2023;27(3):100518.

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