Phantom Pain
Author(s): Thiru M. Annaswamy, MD, Brigid S Deck, BS, Annie Du, BA Originally published: November 11, 2011 Last updated: April 29, 2026
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Patho-anatomy/physiology Essentials of Assessment Rehabilitation Management and Treatments Cutting Edge/emerging and Unique Concepts and Practice Gaps in the Evidence-Based Knowledge Gaps in the Evidence-Based Knowledge References
Definition
Phantom sensation is any non-painful perception originating from the missing limb. Specifically, phantom limb pain is a noxious sensory perception of pain in the limb that is physically not present.
It is important to distinguish phantom limb pain and residual limb pain. Residual limb pain, previously called stump pain, is pain localized to the actual residual limb, which can be caused by intrinsic (e.g., nerve entrapment, neuroma formation, infection, edema) and/or extrinsic factors (e.g., poorly fitted prosthesis).
Etiology
Phantom limb sensation may be present because of spinal cord injury, amputation, or congenital deficiency. Phantom pain is almost exclusively experienced after amputation. It has also been observed after surgical removal of organs such as the breast, eye, penis, and tongue. Phantom limb pain is rarely reported in individuals with congenital limb absence.7
Epidemiology including risk factors and primary prevention
Over 2 million people in the United States are estimated to currently live with limb loss, with 91% having lower extremity amputation and 9% having upper extremity amputation. Over half of amputations are due to micro- and macro-vascular complications from diabetes and peripheral vascular disease, followed by traumatic injury and cancer, respectively..1
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Phantom limb pain is experienced by up to 80% of post-amputation patients, often starting within the first week after amputation. Children and congenital amputees reportedly experience phantom pain much less frequently. In the adult population, age, gender, side, and cause of amputation do not influence the occurrence of phantom limb pain.
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There is a greater incidence of phantom limb pain in shorter residual limbs, lower extremity amputations, and in bilateral amputations.2 Evidence shows that patients with history of infection/gangrene experienced greater phantom limb pain and increased interval between amputation and prosthesis fitting.3 This phenomenon is also especially prevalent in patients experiencing pain in the amputated limb prior to its amputation..2 Phantom limb pain has been reported to have severe pain related functional impairment and diminished quality of life in 25% to 50% of patients.4
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Pre-amputation care should involve a multidisciplinary team to set expectations around post-amputation pain, evaluate physical and psychosocial status, and optimize comorbidities that may affect healing.
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Evidence for pharmacologic prevention of phantom limb pain is limited.Guidelines from the Department of Veteran Affairs, for example, do not clearly support or refute modalities such as gabapentin, pregabalin, ketamine (NMDA antagonists), or calcitonin, though they are sometimes used as part of multimodal perioperative regimens.21,22
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Regional techniques for prevention of phantom limb pain may involve providing perioperative analgesia, including perineural catheters for continuous local anesthetic infusion or epidural analgesia (particularly for lower-extremity amputations).21
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Surgical strategies may play a role in primary prevention. Prophylactic regenerative peripheral nerve interface (PRPNI) is a surgical technique that involves providing transected nerves with muscle grafts to innervate at the time of amputation. This approach is thought to reduce neuroma formation and may help mitigate the peripheral and central mechanisms that contribute to phantom limb pain.5
Patho-anatomy/physiology
The pathophysiology of phantom limb pain is not completely understood. While phantom limb pain has previously been classified as a psychiatric diagnosis, it is now hypothesized that peripheral factors, spinal plasticity, and cerebral reorganization all contribute to the development of phantom limb pain.6
Peripheral Factors
Sprouting, in which Aβ and C fiber endings expand in an unstructured manner, occurs after nerves are resected. Unstructured axon regeneration during sprouting may lead to neuromas, driving hyperexcitability of nociceptive neurons. Nerve fibers within neuromas may exhibit increased ectopic, or spontaneous, activity as well as become hypersensitive to mechanical and chemical stimuli.7,8
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Upregulation of voltage-gated sodium channels within neuromas may also contribute to nerve hyperexcitability.7
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Dorsal root ganglion may also exhibit ectopic activity from the neuroma and further pain sensations by depolarizing neighboring neurons,7,8
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External factors such as temperature, oxygenation, and residual limb or neuroma inflammation may also be involved in the development and severity of phantom limb pain sensations.8
Central Factors
Lamina II of the dorsal horn, corresponding to the substantia gelatinosa, is typically involved in modulating noxious stimuli, determining which incoming stimuli will be interpreted as painful or non-painful. Lamina III and IV involve non-noxious sensory information processing from Aß axons entering dorsal root fibers, which carry predominantly low-threshold, non-noxious information.7
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After injury, C fibers in lamina II are degenerated. In their place, Aβ fibers begin to sprout. As a result, neurons in lamina II, which typically receive high threshold signals from C fibers, begin to receive low threshold signals, leading to perception of non-noxious stimuli as nociceptive and release of neuropeptides such as substance P. This may therefore cause allodynia.7
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Induced inhibition from injury to GABA and glycine interneurons may also cause increased nociception and spinal hyperexcitability.8
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Brain-derived neurotrophic factor (BDNF) may also play a role in modulating excitatory effects on nociception by switching the interneurons from inhibitory to excitatory.8
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Hyperactivation of NMDA receptors may also play a role in persistent phantom limb pain.8
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Cortical reorganization of the primary somatosensory cortex occurs after amputation, and functional magnetic resonance imaging (fMRI) has shown a direct correlation between the pain level and degree of reorganization.8
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Studies have found that patients with depression are associated with more severe phantom limb pain sensation. Serotonin, which is involved in pain modulation, is decreased in depression and thus may contribute to increased severity and sensitivity of phantom limb pain.8
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Anxiety, through increased central nervous system activity, may activate the amygdala and somatosensory cortex, which may increase perception of phantom limb pain.8
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Like other chronic pain conditions, the persistence of phantom pain is most likely a multifactorial process driven by somatic, psychological, and social factors.
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Disease progression including natural history, disease phases or stages, disease trajectory (clinical features and presentation over time)
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There are no distinct stages of phantom pain. Most patients begin experiencing phantom sensation within a week of amputation.
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Phantom limb pain may gradually diminish over time without interventions. Other patients may develop chronic pain syndrome with prolonged or constant phantom limb pain despite therapy.7
Specific secondary or associated conditions and complications
Should symptoms persist or worsen, consider pain from neuromas, soft tissue infections, osteomyelitis, heterotopic ossification, radiculopathy, peripheral vascular disease, peripheral nerve injury, or if the amputation was a result of malignancy, recurrence.
Essentials of Assessment
History
Indications for amputation, pre-amputation and post-amputation pain characteristics should be elucidated. As in any evaluation of pain, it is important to consider pain intensity, location, quality, duration and timing and modulating factors.
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Phantom limb pain is generally localized in the more distal parts of the missing limb, such as wrist, palms, fingers, ankles, feet and toes. The sensations can be described as itching, burning, stabbing, prickling, shooting, twisting, telescoping, vice-like and cramping. Phantom limb pain is usually intermittent and lasts from seconds to minutes, but can last for hours, or even permanently.7
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When interviewing patients, it is advisable to include questions about how the pain has affected the patient’s activities of daily living. Since pain can both cause and exacerbate mental and physical distress, a review of psychological symptoms is also relevant.
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Differential diagnoses should include neuroma formation, arthritis, osteomyelitis, heterotrophic ossification, and septic arthritis.
Physical examination
A physical examination should first assess for any evidence of residual limb pain. Inspect the skin around and joint above the residual limb for signs of wounds or infection.
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A thorough neurological and vascular examination of all extremities is essential. The range of motion, length and circumference of the residual limb must also be measured. Assess upper extremity function if the lower extremity is the amputated site. Observe range of motion and sensory and motor function bilaterally. Evaluate prosthesis as well as fit and number of ply socks utilized.
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If lower extremity is involved, evaluate the patient’s gait. Phantom limb pain may sometimes be elicited by tapping over existing neuromas.
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The examination should evaluate other potential sources of pain, including neuromas, wounds on the residual limb, fractures, stroke, lumbar radiculopathy, myofascial pain, and other peripheral nerve syndromes.
Functional assessment
Phantom limb pain may affect a variety of functional activities such as mobility, activities of daily living, recreational activities and sleeping. It may lead the patient to decrease or discontinue the use of the prosthesis. It may also affect cognitive, emotional, interpersonal and vocational status.
Laboratory studies
Complete blood count (CBC) may show elevated white cell count and neutrophils.
- Abnormal erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) may indicate infection.
Imaging
Plain films of the limb may be useful to evaluate the bony elements in the extremity. Plain x-ray is the preferred modality to diagnose heterotrophic ossification.
- MRI or ultrasound may be used if there is concern for a neuroma or soft tissue abscess/infection. MRI may also reveal additional sources of pain such as scar tissue or osteomyelitis. MRI with and without contrast is preferred for evaluation of osteomyelitis and soft tissue infection but without contrast can be adequate if contrast is contraindicated. Ultrasound is an economical and viable option to assess for most of the conditions in case MRI is unavailable or contraindicated.
Supplemental assessment tools
Vascular and electrodiagnostic studies may be useful in evaluating the differential diagnoses of peripheral vascular disease or nerve damage.
Early predictions of outcomes
Research suggests that duration and intensity of pre-amputation pain and perioperative pain are predictors of future phantom pain, with longer duration and greater severity leading to a greater risk of future development of phantom pain.10 The severity of pain can also be partially predicted by preamputation scores of anxiety and depression. 11
Social role and social support system
Psychosocial dysfunction and depression are seen more frequently in patients suffering from chronic pain, and this is also true with phantom limb pain. Although phantom limb pain is not considered a psychological disturbance, it may be modulated by psychosocial factors. Psychological evaluation and support may be useful.
Rehabilitation Management and Treatments
Available or current treatment guidelines
While there are no specific clinical guidelines for the management and treatment of phantom limb pain, a multidisciplinary approach to phantom limb pain patient care is essential and should include proper residual limb care and management, proper prosthetic fit and alignment, and physical therapy.
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These approaches should be integrated with all aspects of pain management and tailored to each individual, which can combine pharmacologic, physical and interventional modalities, as well as behavioral approaches.
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Current guidelines cite insufficient evidence to recommend for or against any systemic pharmacologic intervention for the management of phantom limb pain. Commonly used initial therapies can include gabapentin, morphine and amitriptyline, though evidence supporting their efficacy is limited.22 Below we list noninvasive, pharmacologic, minimally invasive and surgical interventions for phantom limb pain, noting the level of support for each.
Noninvasive
Mirror therapy, in combination with exercise therapy and neuromuscular electrical stimulation, has been shown to greatly improve severity of phantom limb pain.6
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Physical modalities, such as massage, active and passive movement, and manipulation may be useful in treating the residual limb.
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Transcutaneous electrical nerve stimulation (TENS) and acupuncture may be helpful, although published evidence is limited.
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Textile, electromagnetically acting residual limb liners are also shown to be therapeutic.12
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Desensitization, biofeedback, cognitive coping strategies, proper prosthetic management are important parts of treatment, as well as skin care and edema management.
Pharmacological
Gabapentin and pregabalin are the most prescribed pharmacological options for frequency and intensity of neuropathic phantom limb pain. However, there is conflicting evidence on their efficacy.6,13
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Opioids, such as morphine and methadone, may be effective in reducing phantom pain, but use has been limited due to side effects and potential for dependence.6
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Tricyclic antidepressants such as amitriptyline, effective in treating neuropathic pain, may also be helpful.6
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Carbamazepine may be helpful in reducing phantom pain.13
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SNRI and SSRIs are increasing in popularity due to better side effect profiles, but there is limited data on its effect on phantom pain.6
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For NSAIDS and acetaminophen, analgesic effects vary.
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Intravenous ketamine and dextromethorphan reduce wind-up-like pain, hyperalgesia and phantom pain. Memantine, another NMDA receptor antagonist, was not shown to be effective in 2 separate trials.6,13
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Intravenous calcitonin has been studied with variable results, with one study showing early postoperative intravenous calcitonin may be effective in reducing phantom pain.9
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Adjuvant intervention with topical agents such as capsaicin cream may be employed to relieve residual limb pain and may ameliorate central phantom limb pain.14
Minimally Invasive
Local steroid injections, dorsal root ganglion blocks, spinal cord stimulators, and intrathecal pumps may be used to selectively block the dermatome affected by the phantom pain, but support for these treatments by clinical research is lacking.
- Percutaneous peripheral nerve stimulation of the sciatic and femoral nerves has been shown to be effective in some studies. However, adequately powered clinical trials are needed.15
Surgical
Neuromas or other causes of pain can be surgically removed. However, residual limb revision should be reserved for cases of obvious pathology.
- More invasive neuromodulation techniques are typically considered a last option for refractory phantom limb pain.16
Patient & family education
As with all chronic pain syndromes, both the patient and family should be counseled in the nature and course of the pain. Residual limb and prosthetic care, relaxation techniques, and coping skills should be emphasized.
Emerging/unique interventions
X-reality-based interventions, including virtual reality (controlling the virtual limb using the residual limb), augmented reality (superimposing the virtual limb over the image of the self), and mixed reality (immersing the image of self into virtual environment) have been used to treat phantom limb pain in a manner similar to mirror therapy. Patients who have undergone X-reality-based interventions have been found to have reduced phantom limb pain, decreased use of pharmacologic pain control, and to have an increase in overall activity level.9
Measurement of patient outcomes
Pain measurement scoring systems such as the phantom limb pain Numeric Rating Scale (NRS) and the Visual Analogue Scale (VAS) are the most common tools for measuring phantom limb pain intensity. However, they fail to capture the multidimensional nature of the condition, such as functional impact. Though multidimensional tools like the McGill Pain Questionnaire provide more detail, they can lack diagnostic clarity between phantom limb pain, phantom limb sensation and residual limb pain. Therefore, it is recommended to use a combination of unidimensional pain scales such as the NRS or VAS alongside multidimensional scales to better evaluate disease impact and to ensure proper clinical interventions aren’t missed.19,20
Cutting Edge/emerging and Unique Concepts and Practice
Neurosurgically placed deep brain stimulators are effective in reducing, but not completely eliminating, phantom limb pain. Analgesic effects and improvement of quality of life after thalamic deep brain stimulation has been demonstrated in patients three years post-amputation.17
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Peripheral neuromodulatory and neuroprosthetic approaches have been tried by utilizing a functional prosthetic with peripheral nerve stimulation in the residual limb.18
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Targeted Muscle Reinnervation (TMR) and Regenerative Peripheral Nerve Interface (RPNI) are two emerging techniques that have utility both in primary prevention and in treating established PLP. TMR is a surgical technique in which peripheral nerves that were transected during amputation are rerouted to nearby redundant motor nerves. TMR has been shown to prevent the formation of neuromas and to decrease both phantom limb pain and residual limb pain.16 RPNI involves implanting transected nerve fascicles within muscle grafts and prevents neuroma formation.5
Gaps in the Evidence-Based Knowledge
At present, no standardized approach to the treatment of phantom limb pain exists. Great advances have been made in starting to understand the roles of the peripheral and central nervous system in phantom pain; however, a conclusive, unified pathophysiology remains elusive.
Although various interventional and non-interventional treatments are currently used and show potential to reduce phantom pain, adequately powered, randomized controlled trials are needed to evaluate outcomes, especially long-term efficacy. Pharmacologic treatments, mostly based on the treatment of neuropathic pain, also require continued study.