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Phantom pain

Vanessa Ip

Supplement №3, Volume II

Phantom pain is chronic and sporadic pain occurring after the amputation of an organ or limb. A high rate of occurrence of around 80% after limb amputation is estimated.1 It is also one of the few medical concepts that cannot be fully explained and confirmed by a single mechanism. Our inability to record actual data from the site of pain makes difficult not only the creation of a scale to quantify and compare the pain experienced, but also any justification for treatment, and further investigation.

Since the term ‘phantom pain’ was coined in the 19th century2, several attempts have been made to explain this phenomenon. Many physicians first postulated that psychological factors generated before amputation cause such pain to exist after amputation. This includes emotional distress such as fear, depression, and denial.3 The success of attempts at therapy through progressive relaxation given to amputees demonstrated a degree of correlation between stress level and pain intensity4. This is also thought to be valid as in daily life experiences, stress levels indeed affect people’s level of pain that can even result in the onset of illnesses such as cramps and migraines5.

Others suggest a biological explanation. The earliest suggested explanations of phantom pain involved nervous damage and neuroma formation. It is thought that a neuroma must arise from the irregularity of nerves fibres as they attempt to repair themselves post-injury by the proliferation of Schwann cells into a full limb’s nerves despite the part itself being physically non-existent. These lesions can cause pain, and so are a potential cause.6 On a molecular level, such spontaneous activity is also thought to be due to the upregulation of sodium ion channels in the site.7 Fortunately, as surgical techniques for amputation improve, clinical neuroma formation can be reduced by procedures such as end-to-end nerve coaptation, which involves suturing to an adjacent nerve that is intact.8 Nevertheless, the incidence of phantom pain remains high amongst amputees. It is therefore questionable whether neuroma formation is a valid explanation of phantom pain. Also, evidence suggested that two-thirds of neuromata formed in the mouth and pharynx do not inflict pain at all.9 This shows that there is a possibility that neuromata’s hypersensitivity might be more of a result of amputation, instead of a definite causative agent of phantom pain itself.

Melzack’s argument that ‘we do not need a body to feel a body or a physical injury to feel pain’ clearly depicts the certainty of perceptions of the phantom limb, and also its pain can be explained biologically. He postulated that a ‘neuromatrix’ exists in the brain in which the perception of having limbs or organs in amputees is due to the operation of the matrix in the absence of actual external sensory input from the amputated site. This can be due to other signals that enter the matrix, such as the spontaneous action of neurons that ‘activated’ messages of pain perception which exist due to the ability of the matrix to store ‘painful memories’10.

Melzack’s argument was certainly a leap forward, though it remains difficult to determine its validity, due to the complexity of brain wiring. Yet studies based on mapping brain activity and phantom pain perception by magnetic response shows that higher levels of cortical reorganisation result in increased levels of phantom pain. One hypothesis is that such shifts might alter neural circuits that control pain or affect nearby pain centres and result in phantom limb pain. It is also possible that the pain is a result of an imbalance of pain messages due to damage to the nervous system as the amputation is performed.11

Another promising approach in the 90s relied upon the existence of ‘somatosensory memories’ created near the time of amputation. It is thought that phantom pain is largely identical to the sensation experienced by the amputee just before the procedure, as the phantom pain described by the amputees corresponds in detail to their previous pain records12. In some cases, amputees even reported having mental images of ‘blood trickling down the phantom limb.’13 At first glance this might seem like a result of psychological memory disorder that causes hallucinations, but it is in fact an example of how the ‘vividness of memory components (regardless of “relevance”) seems also enhanced by emotional arousal’14. The memory complex serves as a trace of information that can lead to the reorganisation of the S1 cortex. This can be due to nerve sprouting or the activation of silent connections that can lead to pain as the spontaneous activity of the nerve that supplies the former region of the limb or organ arises.15 Under this hypothesis, the mechanism of phantom pain is not merely pscyhological. However, as there are clear missing links between the memory complex’s formation and the biological alterations, it is still open to debate. In fact, studies on distraction therapy point more to a psychological explanation, as the amputee claimed that she can ‘switch off’ her phantom pain by distracting herself after training16. This parallelsother studies on the effectiveness of cognitive behavioural therapy in chronic pain patients which reported improvements in pain and disability.17 Under this scenario, it seems that the psychological aspects of the mechanisms causing phantom pain have a biological basis. This demonstrates how the two seemingly distinct mechanisms collectively constitute a single valid mechanism..

But in order to verify the contribution of biological factors to changes in the nervous system, greater detail and more experimental data are needed. This is particularly important as there are already many existing hypotheses on how phantom pain arises, but many lack a detailedexplanation of their proposed idea. Yanagisawa et al.18 investigated the possible relationship between phantom pain and the reorganisation of the sensorimotor cortex by training a brain machine interface (bmi) to decode neural activity of the brain, thereby revealing associated movement of the amputated site. Then the signal is converted to a robotic neuroprosthetic bmi in real time. This can induce plastic change in the cortex that can affect the levels of phantom pain. Results show that associating the prosthetic hand with the neural activity related to the phantom hand increased pain, whilst associating it with the intact hand reduced pain and also decreased the quantity of between phantom pain and sensorimotor cortical plasticity. In fact, this is a rather surprising discovery as many believe that learning to associate the phantom limb with the prosthetics should alleviate pain, since functional restoration would occur and reorganisation through such means would help the body ‘feel’ as if the amputated site is really present with functionality. The rise in pain demonstrates phantom pain. This discovery seems to be related to the effectiveness of ‘mirror therapy’ as the amputees are trained to associate their intact limb movement with the phantom limb using a mirror, so the resulting cortex reorganisation is likely related to the intact hand which reduced pain. Indeed, in an investigation on mirror therapy, 100% of the participants in the mirrored therapy group reported a decrease in phantom pain, whilst 67% of the participants in the mental visualization group reported an increase in pain.19 This demonstrates a clear distinction between mental visualization and mirror therapy as mental visualization relies on changes in the reorganisation of the cortex related to the amputated site, whilst mirror therapy relies on the intact limb as a mirror image that potentially causes mirror neurons to reorganise. This result supports previous findings through imaging, which established that it would be worth investigating cortex reorganisation and plasticity..

As mentioned previously, another way of thinking about phantom pain is to avoid treating biological and psychological explanations as dichotomous. This is because even psychological factors can also be mediated by biological means. After major traumatic events or abusive events over a long period, post-traumatic stress disorder can develop due to the dysregulation of the cns.20 The patient will constantly be in a state of intense fear and helplessness and nociceptor excitation can occur. This can lead to incidence of onset fibromyalgia21 and other chronic pain. Related to phantom sensations, this might be the missing link between phantom pain and traumatic experiences that lead to amputation. But since not all amputations are carried out due to traumatic experiences such as accidents and medical conditions, this hypothesis cannot be generalised as a definite cause of phantom pain.

One question that should be raised is whether emotional and psychological are a cause or consequence of such pain. This is because most analyses on phantom pain being a psychological issue build on the trauma and distress of amputees. Therefore, along with the pain, psychological problems are also seen as an effect post-amputation. This observation may cause people to intuit causation. It is difficult to rule out the possibility that such psychological problems are a consequence of phantom pain, rather than the cause. A study of chronic pain also examined such relationship and reached the conclusion of emotional disturbance as ‘more likely to be a consequence than a cause of chronic pain.’22 This strengthens the argument that psychological problems are unlikely to be the cause of phantom pain, despite differences between.

Stumps are a key site of amputation which could be closely related to the cause of phantom pain. Some have investigated its relationship with phantom pain itself, as thesweating and vasoconstriction at the stump are involved in phantom pain as they can ‘spread’ to the phantom limb if perceived to exist..23 The mechanism behind, however, is relevant to most neurological arguments made on the existence of phantom pain. It is hypothesised that such burning pain is evidence that the sympathetic nervous system is the cause, and hyperactivity of its regional pathways due to vascular alterations could be a cause of such involvement.24

Nevertheless, it is fundamentally important to distinguish between pain due to amputation and phantom pain, as the resultant pain can be due to stump pain in the amputated area instead of pain on the amputated, non-existent area. Therefore, the fact that amputees feel that their phantom limb is really present physically or even visually reveals an element of psychological involvement.

Proponents of both psychological and biological explanations have attempted to theorise the mechanism of phantom pain as a single action. However, treating it as such a straightforward neurological disorder might be to ignore the unique nature of phantom pain as being present in a non-present part of a body. With this in mind, I believe that phantom pain arises from multiple mechanisms that are both neuronal and psychological. These factors can also affect the intensity and duration of phantom pain at later stages, so potential therapies should be investigated on this basis. This includes the fact that psychological problems can be a consequence of phantom pain, which intensifies the pain itself.

Phantom pain is a thought-provoking phenomenon that has reshaped assumptions made based on observations and experimentation. Drawing clear lines via the concept of ‘mind-body dualism’ between psychological factors and biological factors seems to be a general approach to maintain the ‘rigidity’ of biological pathways. Ultimately, psychological mechanisms do not solely operate in perception, but rather determine how stimuli are processed, just like other biological pathways. Despite the difficulty in weighing the importance of both factors comparatively, one can establish the input of both psychological and biological bases in the existence of phantom pain. Research on connexions between the two could prove to be fascinating. There could, for example, be circular mechanisms, such as psychological stress that increases steroid hormone levels that can influence neurotransmission in the cns and pns.25 This might be a source of pain perception in the amputated site and should be further investigated. In conclusion, the multiple mechanisms of phantom pain can be viewed in a discrete and scientific manner, whilst they can be treated as a cross-linked system. With efforts to consider the interactions between the two, such analysis could certainly help to better tackle phantom pain.

  1. Kelly Patrick Anthony Byrne, “Survey of Phantom Limb Pain, Phantom Sensation and Stump Pain in Cambodian and New Zealand Amputees,” Pain Med 12, no. 5 (May 1, 2011): 794–98, doi:10.1111/j.1526-4637.2011.01105.x.↩

  2. Silas Weir Mitchell, Injuries of Nerves and Their Consequences (J.B. Lippincott, 1872).↩

  3. Joel Katz and Ronald Melzack, “Pain ‘Memories’ in Phantom Limbs: Review and Clinical Observations,” Pain 43, no. 3 (December 1, 1990): 319–36, doi:10.1016/0304-3959(90)90029-D.↩

  4. John G. Arena et al., “The Relationship Between Situational Stress and Phantom Limb Pain: Cross-Lagged Correlational Data from Six Month Pain Logs,” Journal of Psychosomatic Research 34, no. 1 (January 1, 1990): 71–77, doi:10.1016/0022-3999(90)90009-S.↩

  5. Khara M. Sauro and Werner J. Becker, “The Stress and Migraine Interaction,” Headache: The Journal of Head and Face Pain 49, no. 9 (2009): 1378–86, doi:10.1111/j.1526-4610.2009.01486.x.↩

  6. Julei C. Fanburg-Smith, “Nerve Sheath and Neuroectodermal Tumors,” in Bone and Soft Tissue Pathology, ed. Andrew L. Folpe and Carrie Y. Inwards (Elsevier Health Sciences, 2010), 193–238.↩

  7. L. Nikolajsen and T.S. Jensen, “Phantom Limb Pain,” British Journal of Anaesthesia 87, no. 1 (July 2001): 107–16, doi:10.1093/bja/87.1.107.↩

  8. Mohammad M. Al-Qattan, “Prevention and Treatment of Painful Neuromas of the Superficial Radial Nerve by the End-to-Side Nerve Repair Concept: An Experimental Study and Preliminary Clinical Experience,” Microsurgery 20, no. 3 (2000): 99–104, doi:10.1002/(SICI)1098-2752(2000)20:3<99::AID-MICR1>3.0.CO;2-Y.↩

  9. Douglas R. Gnepp, Diagnostic Surgical Pathology of the Head and Neck E-Book (Elsevier Health Sciences, 2009).↩

  10. Ronald Melzack, “Phantom Limbs,” Scientific American 266, no. 4 (1992): 120–27.↩

  11. B. Bower, “Brain changes linked to phantom-limb pain.” Science News 147, no. 23 (1995): 357.↩

  12. Katz and Melzack, “Pain ‘Memories’ in Phantom Limbs.”.↩

  13. W. R. Henderson and G. E. Smyth, “PHANTOM LIMBS,” J Neurol Neurosurg Psychiatry 11, no. 2 (May 1948): 88–112, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC497107/.↩

  14. German E. Berrios and Mauricio Sierra, “Flashbulb and Flashback Memories,” in Memory Disorders in Psychiatric Practice, ed. German E. Berrios and John R. Hodges (Cambridge University Press, 2000).↩

  15. H. Flor, “Painful Memories: Can We Train Chronic Pain Patients to ’Forget’ Their Pain?” EMBO Reports 3, no. 4 (April 15, 2002): 288–91, doi:10.1093/embo-reports/kvf080.↩

  16. Marteinn Steinar Jonsson and Keren Fisher, “Phantom Pain—Psychological Conceptualization and Treatment: A Case Report,” Behavioural and Cognitive Psychotherapy 24, no. 3 (July 1996): 275–81, doi:10.1017/S1352465800015125.↩

  17. Judith A. Turner, “Comparison of Group Progressive-Relaxation Training and Cognitive-Behavioral Group Therapy for Chronic Low Back Pain,” Journal of Consulting and Clinical Psychology 50, no. 5 (1982): 757–65, doi:10.1037/0022-006X.50.5.757.↩

  18. Takufumi Yanagisawa et al., “Induced Sensorimotor Brain Plasticity Controls Pain in Phantom Limb Patients,” Nature Communications 7 (October 27, 2016): 13209, doi:10.1038/ncomms13209.↩

  19. Brenda L. Chan et al., “Mirror Therapy for Phantom Limb Pain,” New England Journal of Medicine 357, no. 21 (November 22, 2007): 2206–7, doi:10.1056/NEJMc071927.↩

  20. Samantha Meltzer-Brody et al., “Trauma and Posttraumatic Stress Disorder in Women with Chronic Pelvic Pain,” Obstetrics & Gynecology 109, no. 4 (April 2007): 902, doi:10.1097/01.AOG.0000258296.35538.88.↩

  21. Manfred Zimmermann, “Pathophysiological Mechanisms of Fibromyalgia,” The Clinical Journal of Pain 7, no. 1 (March 1991): S8, https://journals.lww.com/clinicalpain/abstract/1991/03001/pathophysiological_mechanisms_of_fibromyalgia.3.aspx.↩

  22. Ann Gamsa, “Is Emotional Disturbance a Precipitator or a Consequence of Chronic Pain?” Pain 42, no. 2 (August 1, 1990): 183–95, doi:10.1016/0304-3959(90)91161-B.↩

  23. W. K. Livingston, “FANTOM LIMB PAIN: A REPORT OF TEN CASES IN WHICH IT WAS TREATED BY INJECTIONS OF PROCAINE HYDROCHLORIDE NEAR THE THORACIC SYMPATHETIC GANGLIONS,” Arch Surg 37, no. 3 (September 1, 1938): 353–70, doi:10.1001/archsurg.1938.01200030002001.↩

  24. Joel Katz, “Psychophysiological Contributions to Phantom Limbs , Psychophysiological Contributions to Phantom Limbs,” Can J Psychiatry 37, no. 5 (June 1, 1992): 282–98, doi:10.1177/070674379203700502.↩

  25. Katy Vincent and Irene Tracey, “Hormones and Their Interaction with the Pain Experience , Hormones and Their Interaction with the Pain Experience,” Reviews in Pain 2, no. 2 (December 1, 2008): 20–24, doi:10.1177/204946370800200206.↩