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Clinical Features and Mechanisms of Phantom Limb Pain

Original Editor - Jess Bell based on the course by Inger Brueckner
Top Contributors - Jess Bell and Stacy Schiurring

Introduction

Phantom limb pain (PLP) is "a painful sensation in a portion of the body that has been amputated".[1] PLP is common in individuals with amputation,[2][3] with a lifetime prevalence of 76%-87%.[4] However, there is a lack of reliable data on the mechanisms of phantom limb pain and its treatment.[5]

Distinguishing Phantom Limb Pain from Residual Limb Pain and Non-painful Phantom Limb Sensations

PLP is distinct from other pain issues or sensations after amputation, such as residual limb pain and non-painful phantom limb sensations.

This optional video briefly introduces the differences between PLP, residual limb pain and non-painful phantom limb sensations:

[6]

Phantom Limb Pain

As stated, PLP is defined as a painful sensation that occurs in an amputated body part. While we typically think of pain in amputated limbs, it is "also described after loss of an eye, breast, or tooth."[3]

Each person’s experience of PLP is unique and they may report different pain sensations. It may be described as dull, squeezing, crushing, etc. (i.e., more of a nociceptive-type pain) or as sharp, shooting, burning, stabbing, prickling, electric-shock-like, etc. (i.e., more of a neuropathic-type pain).[3]

Ortiz-Catalan[7] distinguishes between nociceptive and neuropathic PLP.

Neuropathic PLP = “pain perceived as arising from the missing limb due to sources other than stimulation of nociceptive fibers that used to innervate the missing limb"[7]

Nociceptive PLP = “pain perceived as arising from the missing limb deterministically by stimulation of nociceptive fibers”[7]

It is important to make this distinction as management approaches vary depending on the type of pain.[7]

Residual Limb Pain

Residual limb pain is “defined as pain felt in the remaining part of the amputated limb”.[8] Most individuals with amputations differentiate between residual limb pain and PLP.[5] It usually occurs near the amputation site[5] and can be described as sharp or burning. Residual limb pain tends to be an issue immediately after surgery, but it can persist for years.[9][10]

Residual limb pain can be categorised as post-surgical, neurogenic, prosthesis-related, arthrogenic, ischaemic / vascular, sympathetically maintained, referred, and secondary to tissue issues (e.g., scar tissue, wounds or skin breakdown, myofascial pain, heterotopic ossification).[10][11]

Non-painful Phantom Sensations

"Phantom sensations are defined as any sensation, excluding pain, of the missing limb".[12]

The majority of individuals with amputation, around 80%,[5] report experiencing non-painful phantom sensations.[12] These sensations are often described as a feeling that the missing limb or body part is still present, even though it is physically gone. Individuals with amputation may report a range of sensations in their phantom limb, including tingling, itching, paraesthesia or numbness.[5]

Non-painful phantom limb sensations can be kinetic (i.e., a sense of movement in the missing limb), kinaesthetic (i.e., an ongoing awareness of the missing limb’s position in space, form, etc.) or exteroceptive (i.e., a sense of touch, pressure, temperature, tingling, tightness, itching, etc. in the missing limb).[5][12]

The "boundary between non-painful and painful sensations in amputees can be blurry, including the adjectives used to describe them [...] painful and non-painful phantom sensations have been suggested to exist on a continuum of intensity, with the former more intense than the latter."[5]

Challenges with Phantom Limb Pain Research

"A major challenge with studying PLP is that, as a pain condition, it is a multifaceted experience which reflects the combined sensory, emotional and cognitive domains."[5]

Each individual has a different experience of pain that is modulated by a range of factors unique to them, including their genetics, psychological factors (stress, anxiety, etc.), pain-related cognitions, and social, environmental and cultural factors.[5]

There are a number of challenges specific to PLP research.[5] For instance, the pain is located in a part of the body that has been removed, and this pain rarely occurs without other sensations (i.e., residual limb pain and non-painful phantom sensations). The nature of the pain experience is unique to each person (i.e., quality, intensity, frequency of pain, etc.), and there are different reasons for amputation (i.e., trauma, infection, vascular disease, cancer, etc.). In addition to these differences, there are methodological challenges within PLP research.[5]

If you would like a detailed discussion of these issues, please see: Making sense of phantom limb pain.[5]

Phantom Limb Pain Risk Factors and Timelines

Various factors are associated with PLP. The most strongly associated factors include residual limb pain, pre-amputation pain and non-painful phantom limb sensations.[2][5][9][12] Boomgaardt et al.[12] note that pre-operative pain may be a factor in early PLP, but not later PLP (i.e., PLP assessed at 6 months).

“The factors that predict early phantom limb pain may not be related to more chronic or late phantom limb pain [...] it may be a different type of pain.” -- Inger Brueckner

Other factors have been associated with PLP. For instance, women are more likely to have PLP and residual limb pain - they also report higher levels of pain.[13] PLP is also reported to be more common in the upper limb than in the lower limb.[9] Various situational, economic, emotional, or physical stresses can cause PLP to worsen,[9] but it's important to note that stress and depression don’t appear to cause PLP.[7] Interrupted sleep affects PLP, with poor sleep quality decreasing pain tolerance.[7] A passive coping style prior to amputation and catastrophising can also impact PLP.[3]

PLP usually starts soon after surgery. For some individuals, it might start as soon as the anaesthetic has worn off,[12] but for some, its onset is delayed:[3]

  • PLP starts within 24 hours of surgery for 50% of individuals with amputation
  • PLP starts within one week for 85% of individuals with amputation
  • there may be a second peak of onset at around 12 months after surgery

PLP tends to decrease in frequency and length in the first 6 months after amputation:[3]

  • 30-40% of patients report severe pain and 25% report moderate pain in the early stages (i.e., days / weeks after surgery)
  • around 10% of individuals will experience ongoing severe pain at six months post-amputation and beyond

It is important to note that the percentage of PLP, residual limb pain and non-painful phantom limb sensations is low in individuals with congenital limb absence and early acquired limb amputation (i.e., before 5 years). While PLP can occur in individuals with congenital amputation, it is often after limb correction surgery.[14]

Proposed Mechanisms of Phantom Limb Pain

Pain is a complex phenomenon and “no single theory can account for all of pain’s complexity.”[7]

A number of theories have been proposed to explain the origins of PLP, but our understanding is still evolving. As our knowledge improves, our treatment approaches may shift. The following sections provide a brief overview of previous and current theories of PLP mechanisms.

Peripheral Factors and Nociception

Neuromas

It has been suggested that neuroma formation is involved in residual limb pain and PLP. Neuromas form when injured or severed nerves attempt to reconnect, resulting in disorganised nerve masses. Neuromas can become overactive, causing spontaneous firing or heightened sensitivity to low-threshold mechanical or chemical stimulation.[12]

However, phantom sensations and PLP often begin before neuromas have the chance to form. Moreover, some individuals with amputation experience pain without visible neuroma or after the removal of a neuroma. This indicates that other factors are involved in PLP.[12]

Dorsal Root Ganglia

Dorsal root ganglia arise from the dorsal root of the spinal nerves and they carry sensory information from the peripheral to the central nervous system.[15] It has been proposed that the dorsal root ganglia become overactive after amputation, causing abnormal discharges and “cross-talk” between neurons.[12]

Sympathetic System

It has also been suggested that, after amputation, sympathetic nerves form pathological connections with sensory nerves and that this “coupling” contributes to PLP.[12]

Central Factors

Central Sensitisation

Another theory is that peripheral nerve injury leads to changes in the central nervous system, resulting in increased activation of dorsal horn neurons, structural changes in primary sensory neurons, decreased inhibition in the spinal cord and "rewiring" of the nervous system, which alters pain transmission.[12]

Cortical Reorganisation

Neuroimaging has demonstrated that, after amputation, cortical reorganisation of the sensorimotor cortex can occur. Thus, areas of the cortex that once received input from the amputated limb may start receiving input from other body parts. For example, areas that used to process sensations from the hand might start processing sensations from the face. This reorganisation, or maladaptive brain plasticity, has been proposed as a possible neurophysiological explanation for PLP.[12][7]

However, this theory has been challenged as it's been found that individuals with PLP can have “preserved cortical representations”.[7]

Stochastic Entanglement

More recently, the theory of stochastic entanglement has been proposed.[16]

It is suggested that, after amputation, there is a mismatch between what the brain expects to feel and what it actually experiences. This is called sensory-motor incongruence. This mismatch or deprivation of somatosensory and motor input "may explain the development of PLP in patients without findings of cortical reorganization."[12]

In the following optional video, Professor Ortiz-Catalan discusses the proposed mechanisms of PLP. See from around 18:12 for his explanation of stochastic entanglement:

[17]

Psychological Factors

While psychological factors have been implicated in various forms of chronic pain, the “interaction between pain and psychological variables is less well documented”[18] in PLP. It has been found that there is a relationship between stress and the onset / exacerbation of PLP.[12] Moreover, psychological factors may impact an individual’s ability to cope with PLP and, thus, affect their function.[12]

Fuchs et al.[18] note that catastrophising appears to worsen PLP.[18] In this study, Fuchs et al.[18] define catastrophising as "a maladaptive cognitive coping style that is characterized by an exaggerated, negative orientation towards pain and anticipation of negative outcomes".[18] However, while emotional factors might modulate PLP, this is less pronounced than in other causes of persistent pain.[12] If you would like a more detailed discussion of the proposed mechanisms of phantom limb pain, please see:

Summary

PLP is a common and complex issue experienced by many individuals after amputation. We still don’t fully understand the mechanisms of PLP - there are probably many factors involved, which may vary between individuals.[12]

"If we don't know the cause [of PLP], that's probably impacting our ability to determine the best treatment for that patient." -- Inger Brueckner[9]

References

  1. ↑ IASP. Current understanding of phantom pain and its treatment. Available from: https://www.iasp-pain.org/current-understanding-of-phantom-pain-and-its-treatment/ (accessed 16 October 2024).
  2. ↑ 2.0 2.1 Limakatso K, Ndhlovu F, Usenbo A, Rayamajhi S, Kloppers C, Parker R. The prevalence and risk factors for phantom limb pain: a cross-sectional survey. BMC Neurol. 2024 Feb 6;24(1):57.
  3. ↑ 3.0 3.1 3.2 3.3 3.4 3.5 3.6 Erlenwein J, Diers M, Ernst J, Schulz F, Petzke F. Clinical updates on phantom limb pain. Pain Rep. 2021 Jan 15;6(1):e888.
  4. ↑ Stankevicius A, Wallwork SB, Summers SJ, Hordacre B, Stanton TR. Prevalence and incidence of phantom limb pain, phantom limb sensations and telescoping in amputees: A systematic rapid review. Eur J Pain. 2021 Jan;25(1):23-38.
  5. ↑ 5.00 5.01 5.02 5.03 5.04 5.05 5.06 5.07 5.08 5.09 5.10 5.11 5.12 Schone HR, Baker CI, Katz J, Nikolajsen L, Limakatso K, Flor H, Makin TR. Making sense of phantom limb pain. J Neurol Neurosurg Psychiatry. 2022 May 24;93(8):833–43.
  6. ↑ Cosi Talks. Phantom Limb Pain, Phantom Limb Sensation, Residual Limb Pain. Available from: http://www.youtube.com/watch?v=XfIoHO46BXM [last accessed 16/10/2024]
  7. ↑ 7.00 7.01 7.02 7.03 7.04 7.05 7.06 7.07 7.08 7.09 Ortiz-Catalan M. The stochastic entanglement and phantom motor execution hypotheses: A theoretical framework for the origin and treatment of phantom limb pain. Front Neurol. 2018 Sep 6;9:748.
  8. ↑ List EB, Krijgh DD, Martin E, Coert JH. Prevalence of residual limb pain and symptomatic neuromas after lower extremity amputation: a systematic review and meta-analysis. Pain. 2021 Jul 1;162(7):1906-1913.
  9. ↑ 9.0 9.1 9.2 9.3 9.4 Brueckner I. Phantom Limb Pain Overview Course. Plus, 2024.
  10. ↑ 10.0 10.1 Evans AG, Chaker SC, Curran GE, Downer MA, Assi PE, Joseph JT, Kassis SA, Thayer WP. Postamputation residual limb pain severity and prevalence: A systematic review and meta-analysis. Plast Surg (Oakv). 2022 Aug;30(3):254-268.
  11. ↑ Oosterhoff M, Geertzen JHB, Dijkstra PU. More than half of persons with lower limb amputation suffer from chronic back pain or residual limb pain: a systematic review with meta-analysis. Disabil Rehabil. 2022 Mar;44(6):835-855.
  12. ↑ 12.00 12.01 12.02 12.03 12.04 12.05 12.06 12.07 12.08 12.09 12.10 12.11 12.12 12.13 12.14 12.15 12.16 12.17 Boomgaardt J, Dastan K, Chan T, Shilling A, Abd-Elsayed A, Kohan L. An algorithm approach to phantom limb pain. J Pain Res. 2022 Oct 26;15:3349-3367.
  13. ↑ Mioton LM, Dumanian GA, Fracol ME, Apkarian AV, Valerio IL, Souza JM, et al. Benchmarking residual limb pain and phantom limb pain in amputees through a patient-reported outcomes survey. Plast Reconstr Surg Glob Open. 2020 Jul 15;8(7):e2977.
  14. ↑ Diers M, Fuchs X, Bekrater-Bodmann R, Flor H. Prevalence of phantom phenomena in congenital and early-life amputees. J Pain. 2023 Mar;24(3):502-508.
  15. ↑ Ahimsadasan N, Reddy V, Khan Suheb MZ, et al. Neuroanatomy, Dorsal Root Ganglion. [Updated 2022 Sep 21]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK532291/
  16. ↑ Limakatso K, Cashin AG, Williams S, Devonshire J, Parker R, McAuley JH. The efficacy of graded motor imagery and its components on phantom limb pain and disability: a systematic review and meta-analysis. Can J Pain. 2023 May 17;7(1):2188899.
  17. ↑ NeuroBioniX. ICPLP2021 - Prof. Ortiz Catalan: Neurogenesis and treatment of PLP. Available from: http://www.youtube.com/watch?v=gNUzsjPDh1s [last accessed 17/10/2024]
  18. ↑ 18.0 18.1 18.2 18.3 18.4 Fuchs X, Flor H, Bekrater-Bodmann R. Psychological factors associated with phantom limb pain: a review of recent findings. Pain Res Manag. 2018 Jun 21;2018:5080123.
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