Author(s): Matthew Adamkin, MD, David Levin, DO, Katrina Slater, DO
Originally published: November 11, 2011 Last updated: June 8, 2023
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Disease/ Disorder

Definition

Phantom pain is a noxious sensory perception of pain in an organ or limb that is physically not present. Stump pain is pain localized in the residual limb, and phantom sensation is the non-painful sensation of the presence of a missing limb.

Etiology

Phantom limb sensation may be present as a result 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 breast, eye, penis, and tongue.

Epidemiology including risk factors and primary prevention

Phantom pain is experienced by up to 80% of post-amputation patients within the first week after amputation, with diminishing incidence over time. More commonly seen in patients suffering from pain in the amputated limb prior to its amputation.1 In the adult population, age, gender, side, and cause of amputation do not influence the occurrence of phantom pain. There is a greater incidence in shorter residual limbs, lower extremity amputations and in bilateral amputees.1,2 Children and congenital amputees experience phantom pain much less frequently. There is also evidence that patients with history of infection/gangrene experienced greater pain and increased interval between amputation and prosthesis fitting.3 Phantom limb pain has been reported to have severe pain related functional impairment and diminished quality of life in 25% to 50% of patients.21

Patho-anatomy/physiology

The mechanism responsible for phantom pain is not completely understood, but it is hypothesized that peripheral factors, spinal plasticity and cerebral reorganization all contribute. Peripherally cut nerves develop neuromas, which show increased sodium channel expression, causing spontaneous and abnormal evoked potentials with sensory stimulation.4 C fibers in the dorsal horn may degenerate after peripheral injury, being replaced with A fibers, leading to an increased expression of substance P, a lower threshold and persistent neuronal discharge. 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.5 Therapy focusing on limb perception (such as mirror therapy and prosthesis use) could prevent, reduce, and even reverse these changes in cortical reorganization.22 The persistence of phantom pain most likely is a multifactorial process driven by somatic, psychological, and social factors (similar to other chronic pain conditions).

Disease progression including natural history, disease phases or stages, disease trajectory (clinical features and presentation over time)

There are no distinct stages of phantom pain. Most patients have a decrease in pain over time. Patients with severe, prolonged phantom pain may develop chronic pain syndrome, with its associated multifactorial impairments.

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. Phantom 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 intermittent burning, stabbing, prickling or shooting. Painful phantom sensations are usually intermittent and last from seconds to minutes, but can last for hours, or even permanently. Generally, pain diminishes in both frequency and duration during the first 6 months after amputation.20 Include questions about symptoms and behavioral changes commonly associated with pain. Since changes in pain can be both cause and effect of affective disturbances, a review of psychological symptoms is relevant.

Physical examination

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. If lower extremity is involved, evaluate the patient’s gait. Phantom pain may be elicited by tapping over existing neuromas. 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 pain may lead the patient to decrease or discontinue the use of the prosthesis; it may also decrease mobility and affect cognitive, emotional, interpersonal and vocational status.

Laboratory studies

Complete blood count (CBC) showing elevated white cell count and neutrophils as well as 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.6 The severity of pain can also be partially predicted by preamputation scores of anxiety and depression.16

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 pain. Although phantom 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

There are no specific clinical guidelines for the management and treatment of phantom limb pain. A multidisciplinary approach to phantom limb patient care is essential. Proper stump care and management must be emphasized. Prosthetic fit and alignment should be addressed. Physical therapy is also an integral part of phantom limb management. These approaches should be integrated with all aspects of pain management, which can combine pharmacologic, physical modalities, interventional, and behavioral approaches.

Noninvasive

  • Physical modalities, such as massage, active and passive movement, and manipulation may be useful in treating the residual limb. Transcutaneous electrical nerve stimulation (TENS) and acupuncture may also be helpful.
  • Mirror box imagery has shown to significantly reduce phantom pain.27
  • Myoelectrical prosthetic use, probably based on visual feedback, can be used. Textile, electromagnetically-acting stump liners are also shown to be therapeutic.8
  • Desensitization, biofeedback, cognitive coping strategies, proper prosthetic management are important parts of treatment, as well as skin care and edema management.

Pharmacological

  • 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.9
  • Intravenous calcitonin has been studied with variable results, including were variable, with one study showing early postoperative intravenous calcitonin may be effective in reducing phantom pain.10
  • NSAIDS and Acetaminophen: Analgesic effects vary.
  • Tricyclic antidepressants, effective in treating neuropathic pain, may also be helpful in treating phantom pain. Side effects include sedation and anticholinergic effects. SNRI and SSRIs are increasing in popularity due to better side effect profile but there is limited data on its effect on phantom pain. 11
  • Anticonvulsants: Gabapentin was found to be effective in decreasing pain intensity, with limiting side effects.23 Carbamazepine and pregabalin may be helpful in reducing phantom pain.
  • Opioids, such as morphine and methadone, are effective in reducing phantom pain. Adjuvant intervention with topical agents such as Capsaicin cream may be employed but has yet to be proven effective in well-controlled trials.12

Minimally invasive

Although local steroid injections, dorsal root ganglion blocks, spinal cord stimulators, and intrathecal pumps may be used to relatively selectively block the dermatome affected by the phantom pain, 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 further research with larger patient cohorts is needed.24

Surgical

Neuromas or other causes of pain can be surgically removed; however, stump revision should be reserved for cases of obvious pathology.

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. Stump and prosthetic care, relaxation techniques, and coping skills should be emphasized.

Emerging/unique interventions

Virtual Reality and Augmented Reality have been used to treat phantom limb pain in a manner similar to mirror therapy. Patients utilize myoelectric controls on their residual limb to control a virtual limb. This has been demonstrated to be effective for the treatment of phantom pain associated with distorted movement and positioning of the phantom limb more so than typical neuropathic pain sensations.17

Low intensity, low frequency, surface acoustic wave ultrasound treatments is currently being investigated. Surface acoustic wave ultrasound, shown to reduce pain in trigeminal neuralgia and other pain syndromes, is currently being evaluated for treating phantom pain.13

Measurement of Patient Outcomes

Standard pain measurements and scoring systems, such as the Visual Analog Scale (VAS), may be applied to phantom limb pain. Although numerous functional outcome measurement instruments exist for amputees, none is specific for phantom pain.

Cutting Edge/ Emerging and Unique Concepts and Practice

Neurosurgically placed deep brain stimulators are effective in reducing, but not completely eliminating phantom pain.  Analgesic effects and improvement of quality of life after thalamic deep brain stimulation has been demonstrated in patients one year post-amputation.14

Peripheral neuromodulatory and neuroprosthetic approaches have been tried by utilizing a functional prosthetic with peripheral nerve stimulation in the residual limb.18

A systematic review of amputation surgical techniques demonstrated that Targeted Muscle Reinnervation (TMR) and Regenerative Peripheral Nerve Interface (RPNI) are effective at prevention of phantom limb pain development.25 TMR is a surgical technique in which amputated nerves are transferred to nearby motor nerves for neuroma prevention has been shown to decrease both phantom limb pain and residual limb pain.19 RPNI involves wrapping a transected nerve in an autologous muscle graft and placing it proximal to the surgical incision to prevent neuroma irritation.25

Gaps in the Evidence-Based Knowledge

At present no evidence-based approach to the treatment of phantom pain exists. In a review of 186 research articles on phantom pain, it was found that only 12 were strong enough to be included, and out of the 12, only 3 were randomized controlled cross-over trials.15 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, large randomized controlled trials are needed to evaluate the outcomes. Pharmacologic treatments, mostly based on the treatment of neuropathic pain, need further study.

References

  1. Kehlet H, Jensen TS, Woolf CJ. Persistent postsurgical pain: risk factors and prevention.Lancet. 2006;367:1618-1625.
  2. Dijkstra PU, Geertzen JH, Stewart R, van der Schans CP. Phantom pain and risk factors: a multivariate analysis. J Pain Sympt Manage. 2002;24(6):578-585.
  3. Weiss SA and Lindell B. Phantom Limb Pain and Etiology of Amputation in Unilateral Lower Extremity Amputees. Journal of Pain and Symptom Management.1996 Jan;11(1):3-17.
  4. Devor M, Seltzer Z. Pathophysiology of damaged nerves in relation to chronic pain. In: Wall PD, Melzack R, eds. Wall and Melzack Textbook of Pain. 4th ed. Edinburgh, UK: Churchill Livingstone; 1999:129-164.
  5. Maclver K, Lyoyd DM, Kelly S, Roberts N, Nurmikko T. Phantom limb pain, cortical reorganization and the therapeutic effect of mental imagery. Brain.2008;131(8):2181-2191.
  6. Richardson C, Glenn S, Horgan M, Nurmikko T. A prospective study of factors associated with the presence of phantom limb pain six months after major lower limb amputation in patients with peripheral vascular disease. J Pain. 2007;8(10):793-801.
  7. Purushothaman S, Kundra P, Senthilnathan M, Sistla SC, Kumar S. Assessment of efficiency of mirror therapy in preventing phantom limb pain in patients undergoing below-knee amputation surgery-a randomized clinical trial. J Anesth. 2023 Feb 21. doi: 10.1007/s00540-023-03173-9. Epub ahead of print. PMID: 36809505.
  8. Kern U, Altkemper B, Kohl M. Management of phantom pain with a textile, electromagnetically-acting stump liner: a randomized, double-blind, crossover study.J Pain Sympt Manage. 2006;32(4):352-360.
  9. Maier C, Dertwinkel R, Mansourian N. Efficacy of the NMDA-receptor antagonist memantine in patients with chronic phantom limb pain: results of a randomized double-blinded, placebo-controlled trial. Pain. 2003;103:277-283.
  10. Erlenwein J, Diers M, Ernst J, Schulz F, Petzke F. Clinical updates on phantom limb pain. Pain Rep. 2021 Jan 15;6(1):e888. doi: 10.1097/PR9.0000000000000888. PMID: 33490849; PMCID: PMC7813551.
  11. Knotkova H, Cruiciani R, Tronnier V, Rasche D. Current and future options for management of phantom-limb Pain. Current and future options for management of phantom-limb Pain. JPR. 2012:39. Doi:10.214/jpr.s16733
  12. Rayner HC, Atkins RC, Westerman RA. Relief of local stump pain by capsaicin cream. Lancet 1989; 2: 1276–7.
  13. Krouskop, T. A pulsed Doppler ultrasonic system for making noninvasive measurements of the mechanical properties of soft tissue. Available at: http://www.rehab.research.va.gov/jour/87/24/2/pdf/krouskop.pdf.
  14. Pereira E. Thalamic deep brain stimulation for neuropathic pain after amputation or brachial plexus avulsion. National Center for Biotechnology Information. Available at: http://www.ncbi.nlm.nih.gov/pubmed/23991820.
  15. Halbert J, Crotty M, Cameron ID. Evidence for optimal management of acute and chronic phantom pain: a systematic review. Clin J Pain. 2002;18:84-92. 
  16. Larbig W, Andoh J, Huse E, Stahl-Corino D, Montoya P, Seltzer Z, Flor H. Pre- and Postoperative Predictors of Phantom Limb Pain. Neuroscience Letters. 2019; 702:44-50.
  17. Osumi M, Inomata K, Inoue Y, Otake Y, Morioka S, Sumitani M. Characteristics of Phantom Limb Pain Alleviated with Virtual Reality Rehabilitation. Pain Medicine. 2019; 20(5):1038-1046.
  18. Petersen B, Nanivadekar A, Chandrasekaran S, Fisher L. Phantom Limb Pain: Peripheral Neuromodulatory and Neuroprosthetic Approaches to Treatment. Muscle & Nerve. 2019; 59(2):154-167
  19. Valerio I, Dumanian G, Jordan S, Mioton L, Bowen J, West J, Porter K, Ko J, Souza J, Potter B. Preemptive Treatment of Phantom and Residual Limb Pain with Targeted Muscle Reinnervation at the Time of Major Limb Amputation. Journal of the American College of Surgeons. 2019; 228(3):217-226.
  20. Desmond DM, Maclachlan M. Prevalence and characteristics of phantom limb pain and residual limb pain in the long term after upper limb amputation. Int J Rehabil Res 2010;33:279–82.
  21. Ehde DM, Czerniecki JM, Smith DG, Campbell KM, Edwards WT, Jensen MP, Robinson LR. Chronic phantom sensations, phantom pain, residual limb pain, and other regional pain after lower limb amputation. Arch Phys Med Rehabil 2000;81:1039–44.
  22. Flor H. Phantom-limb pain: characteristics, causes, and treatment. Lancet Neurol 2002;1:182–9.
  23. Alviar MJ, Hale T, Dungca M. Pharmacologic interventions for treating phantom limb pain. Cochrane Database Syst Rev 2016:CD006380. 
  24. Gilmore C., Ilfeld B., Rosenow J., Li S., Desai M., Hunter C., Rauck R., Kapural L., Nader A., Mak J., et al. Percutaneous peripheral nerve stimulation for the treatment of chronic neuropathic postamputation pain: A multicenter, randomized, placebo-controlled trial. Reg. Anesth. Pain Med. 2019;44:637–645. doi: 10.1136/rapm-2018-100109. 
  25. J.W.D. de Lange, C.A. Hundepool, D.M. Power, V. Rajaratnam, L.S. Duraku, J.M. Zuidam, Prevention is better than cure: Surgical methods for neuropathic pain prevention following amputation – A systematic review, Journal of Plastic, Reconstructive & Aesthetic Surgery, Volume 75, Issue 3, 2022, Pages 948-959, ISSN 1748-6815, https://doi.org/10.1016/j.bjps.2021.11.076. (https://www.sciencedirect.com/science/article/pii/S1748681521006288)

Original Version of the Topic:

Matthew Medwick, MD. Phantom Pain. Publication Date: 11/11/2011.

Previous Revision(s) of the Topic

David Haustein, MD, Preeti Panchang, MD. Phantom Pain. 4/19/2016

Matthew Adamkin, MD. Phantom Pain. 4/19/2016

Author Disclosure

Matthew Adamkin, MD
Nothing to Disclose

David Levin, DO
Nothing to Disclose

Katrina Slater, DO
Nothing to Disclose