Deafferentation Pain
Deafferentation pain is a distinct and challenging category of neuropathic pain. Its defining characteristic is the partial or complete interruption (deafferentation) of normal afferent sensory input from a specific body part to the central nervous system (CNS). It arises from dysfunction within the nervous system itself, rather than from the activation of nociceptors by tissue damage or inflammation.[1]
Deafferentation pain syndromes represent a significant clinical challenge for pain and musculoskeletal physicians due to their complex pathophysiology, often severe and persistent nature, and frequent refractoriness to conventional treatments.
Terminology
Neuropathic Pain: The term "neuropathic pain," as defined by the International Association for the Study of Pain (IASP), is the preferred overarching classification: "An unpleasant sensory and emotional experience associated with, or resembling that associated with, actual or potential tissue damage".
Deafferentation pain: The term "deafferentation pain" is used more specifically within this category to emphasize the critical pathophysiological element of sensory input loss.
Deafferentation vs neurectomy: Considering neuropathic pain following limb amputation is useful in thinking about the differences between neurectomy and deafferentation. While limb amputation does involve nerve transection (neurectomy), the resulting pain syndrome is classically considered examples of deafferentation pain.
- Deafferentation (Phantom Limb Pain): This type of pain arises as a consequence of the loss (partial or complete interruption) of normal sensory input from a body part to the central nervous system. Limb amputation inherently causes a loss of sensory input from the missing limb, and this lack of normal input triggers maladaptive plastic changes within the CNS (both the brain and spinal cord). These central changes include neuronal hyperexcitability, central sensitization, and cortical reorganization. Thus PLP, the pain perceived as originating from the missing limb, is considered the archetypal example of deafferentation pain resulting from these central changes driven by the loss of input.
- Neurectomy (Residual Limb Pain): Patients can also get Residual Limb Pain (RLP) from the neurectomy, also called neuroma pain.This type of pain is primarily driven by peripheral mechanisms resulting directly from the nerve transection itself. When a peripheral nerve is cut, the proximal end attempts to regenerate, often forming a disorganized mass of nerve sprouts called a neuroma. These neuromas, along with the damaged nerve endings at the stump, can become hyperexcitable and generate spontaneous, abnormal electrical signals (ectopic discharges). This peripheral activity is thought to be the main driver of pain localized to the residual limb (stump), often referred to as RLP or neuroma pain. It's typically characterized by localised tenderness, sharp or shooting pain, and may be exacerbated by pressure on the stump or neuroma.
Your point about the DRG is important. Deafferentation pain can result from damage or loss of the DRG, as seen in conditions like brachial plexus avulsion where the nerve roots (including the DRG) are torn from the spinal cord.
However, the definition of deafferentation pain hinges on the interruption of afferent signal flow, not necessarily the destruction of the DRG itself. In a typical limb amputation, the peripheral axon is severed distal to the DRG, and the DRG cell body often survives. Despite the DRG remaining largely intact, the cessation of normal sensory input from the limb constitutes deafferentation, leading to the central nervous system changes that underlie PLP. Furthermore, deafferentation pain can also arise from central lesions like stroke or spinal cord injury, where the DRGs are unaffected but central somatosensory pathways are damaged.
The Paradox of Pain with Sensory Loss
A central and often perplexing clinical feature of deafferentation pain is its paradoxical presentation: patients experience significant, often spontaneous, pain that is localized to a body region exhibiting markedly reduced or entirely absent sensation (hypoesthesia/anesthesia, hypoalgesia/analgesia) to external stimuli. This contrasts sharply with nociceptive pain, where pain intensity generally correlates with stimulus intensity and relies on intact sensory pathways. Patients may describe severe burning, shooting, or aching sensations in an area that feels numb or has diminished sensitivity to touch, pinprick, or temperature.[2]
An extreme manifestation of this paradox is Anesthesia Dolorosa (AD), literally "painful numbness". AD is characterized by constant, severe, often burning or aching pain felt within an area that is completely numb to all sensory modalities. It most commonly occurs as a complication following surgical or traumatic injury to the trigeminal nerve.
The coexistence of pain and sensory loss is more than just a clinical curiosity; it serves as a crucial diagnostic pointer. It strongly suggests that the pain mechanism is not driven by ongoing peripheral nociception but rather by pathological changes within the somatosensory pathways themselves, consequent to the loss of normal input. The nervous system, deprived of its usual sensory signals, undergoes maladaptive changes that generate aberrant pain signals centrally.[1]
Aetiology
Injuries or diseases primarily affecting the peripheral nervous system are common causes of deafferentation pain.
Peripheral Causes
Injuries or diseases primarily affecting the peripheral nervous system are common causes of deafferentation pain.
Limb Amputation: This is perhaps the most widely recognized cause, leading to Phantom Limb Pain (PLP), where pain is perceived as originating from the missing limb. PLP is a classic example of deafferentation pain, occurring in a high percentage of amputees.
Peripheral Nerve Injury/Avulsion: Traumatic injuries causing complete or partial severance, stretching, or avulsion (tearing away from the spinal cord) of peripheral nerves or plexuses are significant causes. Brachial plexus avulsion (BPA), often resulting from high-velocity trauma, is particularly notorious for causing severe, intractable deafferentation pain in the affected arm. Painful traumatic mononeuropathies can also have a deafferentation component.
Postherpetic Neuralgia (PHN): Following an outbreak of herpes zoster (shingles), the varicella-zoster virus can damage sensory nerves and ganglia, leading to persistent neuropathic pain in the affected dermatome. This often involves significant sensory loss, classifying it as a deafferentation syndrome.
Painful Polyneuropathies: While many polyneuropathies (e.g., diabetic neuropathy) involve ongoing nerve dysfunction and inflammation, severe forms with significant axonal loss can lead to substantial sensory deficits. When pain coexists with this sensory loss, a deafferentation mechanism likely contributes to the overall pain picture.
Post-Surgical Pain/Neurectomy: Surgical procedures can inadvertently damage peripheral nerves. Furthermore, intentional nerve transection (neurectomy) or ablation procedures, sometimes performed to treat other pain conditions (like trigeminal neuralgia), can themselves result in deafferentation pain. Anesthesia Dolorosa, severe pain in a numb area of the face, is a dreaded complication specifically associated with procedures targeting the trigeminal nerve or ganglion. Phantom tooth pain following dental extraction or root canal treatment is another example.[3]
Central Causes
Lesions within the brain or spinal cord that disrupt somatosensory pathways are major causes of central deafferentation pain.
Spinal Cord Injury (SCI): SCI is a very frequent cause of chronic pain, much of which is neuropathic. Deafferentation pain following SCI typically occurs below the level of the lesion, resulting from the interruption of ascending sensory tracts (e.g., spinothalamic tract). Individuals with SCI have the highest risk of developing central neuropathic pain (CNP).[4]
Stroke: Cerebrovascular accidents causing damage to central somatosensory structures are a leading cause of CNP globally.[4] Lesions involving the thalamus (particularly the ventral posterior nucleus) can lead to the classic "thalamic pain syndrome" (Dejerine-Roussy syndrome), but lesions in the brainstem, internal capsule, or somatosensory cortex can also result in Central Post-Stroke Pain (CPSP) with deafferentation features.
Multiple Sclerosis (MS): This autoimmune disease causes demyelinating plaques within the CNS. When these lesions affect somatosensory pathways (e.g., spinal cord tracts, brainstem, thalamus), they can produce central neuropathic pain, often with associated sensory loss, consistent with a deafferentation mechanism.
Brain Injury: Traumatic brain injury (TBI) or damage from neurosurgical procedures affecting central sensory processing areas can also lead to deafferentation pain.[4]
Syringomyelia: The formation of a fluid-filled cavity (syrinx) within the spinal cord can disrupt crossing spinothalamic fibers and other sensory pathways, causing pain and sensory loss, sometimes manifesting as deafferentation pain.
Pathophysiology
The pathophysiology of deafferentation involves a cascade of maladaptive plastic changes occurring at multiple levels of the neuraxis following the loss of normal sensory input. It is a disease of the nervous system itself. Several key processes have been identified that transform the somatosensory system from one that faithfully relays sensory information to one that generates spontaneous pain and exhibits pathologically amplified responses to stimuli.
Key Pathophysiological Changes in Deafferentation Pain
| Nervous System Level | Key Mechanisms | Consequence/Contribution to Pain Phenotype |
| Peripheral | Spontaneous pain signals; lowered firing threshold; peripheral sensitization; contribution to central sensitization | |
| Spinal Cord | Lowered pain thresholds; allodynia; hyperalgesia; expanded receptive fields; spontaneous pain; impaired pain modulation; maintenance of chronic pain state | |
| Supraspinal | Spontaneous pain; altered sensory processing; potential contribution to pain intensity (correlation); altered pain perception (sensory/affective); sensory-motor conflict; widespread network dysfunction |
PNS Contributions
Spinal Cord Contributions
Supraspinal Contributions
Maladaptive Plasticity and Cortical Reorganization
Clinical Features
References
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|date=(help) - ā 2.0 2.1 Finnerup, Nanna Brix; Kuner, Rohini; Jensen, Troels Staehelin (2021-01-01). "Neuropathic Pain: From Mechanisms to Treatment". Physiological Reviews (in English). 101 (1): 259ā301. doi:10.1152/physrev.00045.2019. ISSN 0031-9333.
- ā Marbach, Joseph J.; Raphael, Karen G. (2000-03). "Phantom Tooth Pain: A New Look at an Old Dilemma". Pain Medicine (in English). 1 (1): 68ā77. doi:10.1046/j.1526-4637.2000.00012.x. ISSN 1526-2375. Check date values in:
|date=(help) - ā 4.0 4.1 4.2 Rosner, Jan; Andrade, Daniel C. de; Davis, Karen D.; Gustin, Sylvia M.; Kramer, John L. K.; Seal, Rebecca P.; Finnerup, Nanna B. (2023 Dec 21). "Central neuropathic pain". Nature reviews. Disease primers (in English). 9 (1): 73. doi:10.1038/s41572-023-00484-9. PMID 38129427. Check date values in:
|date=(help) - ā 5.0 5.1 5.2 Costigan, Michael; Scholz, Joachim; Woolf, Clifford J. (2009-06-01). "Neuropathic Pain: A Maladaptive Response of the Nervous System to Damage". Annual Review of Neuroscience. 32 (1): 1ā32. doi:10.1146/annurev.neuro.051508.135531. ISSN 0147-006X.
- ā Cohen, Steven; Hsu (2013-02). "Postamputation pain: epidemiology, mechanisms, and treatment". Journal of Pain Research: 121. doi:10.2147/jpr.s32299. ISSN 1178-7090. Check date values in:
|date=(help) - ā Moore, Christopher I.; Stern, Chantal E.; Dunbar, Carolyn; Kostyk, Sandra K.; Gehi, Anil; Corkin, Suzanne (2000-12-12). "Referred phantom sensations and cortical reorganization after spinal cord injury in humans". Proceedings of the National Academy of Sciences. 97 (26): 14703ā14708. doi:10.1073/pnas.250348997. ISSN 0027-8424.
- ā Anderson, Keri; Stein, Sebastian; Suen, Ho; Purcell, Mariel; Belci, Maurizio; McCaughey, Euan; McLean, Ronali; Khine, Aye; Vuckovic, Aleksandra (2025-01-16). "Generalisation of EEG-Based Pain Biomarker Classification for Predicting Central Neuropathic Pain in Subacute Spinal Cord Injury". Biomedicines. 13 (1): 213. doi:10.3390/biomedicines13010213. ISSN 2227-9059.
