Phantom pain – a biological basis or a ghost in the machine?

By Samrah Siddiqi

Phantom limb pain is an elusive syndrome which has, for centuries, mystified many. In the mid-16th century, it was first described amongst wounded soldiers and patients whose limbs had been amputated due to conflict, accident, or infection. They would describe the sensation as if their lost limbs were still present. According to recent research, this unique type of pain has presented itself in 50-80% of amputees (Perur, 2014), manifesting itself as a “shooting, stabbing, burning or electric shock-like” pain (Tobin, 2014) that never goes away. Theories explaining the cause of this highly individual pain sensation were originally centred around a psychological response of the mind to the loss of a limb, otherwise known as a ‘ghost in the machine’, associated with somewhat spiritual and emotional connections. However, with increasing experimental evidence, a potential biological basis for this phenomenon has come to the forefront. To explore the cause of phantom limb pain in more detail, one must understand the complex phenomenon of normal pain. The perception of pain in the brain impacts how we experience pain and the level of intensity of this experience. This psychological response can be likened to a thermostat modifying the pain signal.

The “gate control” theory of pain (Melzack & Wall, 1965) argues that distracting the mind from pain can reduce the level of the pain’s intensity. Research has shown that this could be a consequence of stimulation of the periaqueductal grey matter, thus creating a pain-relieving effect. The causes of normal pain differ from that of phantom pain as normal pain is thought to have a sensory origin as opposed to the psychological explanations proposed by researchers for phantom pain. Researchers found it difficult to pinpoint an obvious source for the phantom pain, so early research attempted to associate the cause and intensity of this pain with the amputee’s personality. Psychologist Marianne Simmel investigated the link between phantom pain and the amputee’s emotional distress and anxiety resulting from the loss of the body part and found that “seventy-four per cent of subjects demonstrated some significant stress-pain relationship” (Arena et al., 1990). However, this was subsequently challenged by the research of Shukla et al. (1982) which revealed that there were no significant differences between the personalities of amputated people who experience phantom limb pain and those who do not. To date, no research has been able to prove a causal relationship between phantom limb pain and negative emotions due to the difficulty in devising an experiment which overcomes emotional bias.

The role of psychology in pain perception and pain relief cannot, however, be entirely dismissed. Pain trials have shown that placebo treatments are able to help approximately 30-70% of patients when a definitive cause of the pain is identified (Physical Medicine and Rehabilitation Clinic, 1995). This shows that there must be an expectation component involved in pain perception and relief, and that it is not just a cause and effect mechanism. A patient suffering from phantom limb syndrome is arguably expecting to experience pain as a result of the amputation. Likewise, patients receiving placebo treatment expect the “fake” drug to alleviate their pain to a certain degree and therefore feel better, regardless of the drug having any chemical bases for such an effect.

As research has advanced in recent decades, evidence for a biological basis for phantom pain has accumulated. A multitude of neurobiological theories have been put forward in order to explain the cause of this mysterious syndrome. These theories overlap to a certain extent and can be categorised into three sub-divisions: spinal, central and peripheral mechanisms. Initially, researchers postulated that the phantom pain sensations might arise in the peripheral nervous system at the amputation site. Furthermore, this theory suggested that the severed nerve endings at the amputation site produced neurotransmitters which subsequently sensitised peripheral pain receptors, producing phantom pain. However, attempts to inject local anaesthetic or remove further tissue did not eliminate the pain. Therefore, this theory was deemed inconclusive.

An alternative theory for the biological basis of phantom pain was proposed in 2009 – “the proprioceptive memory theory” (Anderson-Barnes et al., 2009). The theory describes the cause of phantom pain as a “conflict between vision and memory. The brain remembers the positions of the limb and its relation to the body and other limbs (based on proprioception), but the eyes do not see the limb” (Bennington-Castro, J., 2013). They observed that when a patient saw a reflection of their surviving limb superimposed over their missing limb, they reported an increase in the relief of their phantom limb pain. As a result, Anderson-Barnes et al. (2009), hypothesised that the mirror image helps to resolve the conflict between the patients’ visual and memory systems. Neuroscientist, V.S. Ramachandran, also performed a similar experiment using a mirror box to manipulate neuroplasticity and trick the brain into thinking that the missing limb was present. Movement of the intact limb in the mirror would prove to the brain that the phantom limb was also moving and, more importantly, prove that it was present. Performing this action repeatedly induced immediate pain relief.

Nevertheless, whilst several randomised controlled trials of this attempted treatment have been successful, others have yet to provide a considerably high level of evidence. The last three decades of research have increasingly led to the understanding that different parts of the central nervous system work in conjunction with one another to create phantom pain sensations. However, the evidence for how phantom pain arises is still inconclusive. The “study of how physical stimuli are translated into psychological experience”, also known as psychophysics, has attempted to bring the two concepts closer together (Marguc, 2010). Psychophysics states that stimuli are translated by our brain into something significant – in the case of phantom limb syndrome, phantom pain. After amputation surgery, ectopic discharges tend to form at injured sites of peripheral nerves. This has been seen to be translated by the brain as neuropathic pain.

The evidence so far suggests that even psychological explanations for phantom pain are being based on electrochemical interactions in the body. Fundamentally, phantom pain has a biological basis but there are integral psychological aspects which may also play a role in how the phantom pain is perceived.

References:

Anderson-Barnes, V.C., McAuliffe, C., Swanberg, K.M., Tsao, J.W. (2009) Phantom limb pain–a phenomenon of proprioceptive memory? Medical hypotheses. Available from: <https://www.ncbi.nlm.nih.gov/pubmed/19556069&gt; [Accessed 26 October 2020]

Arena, J.G., Sherman R.A., Bruno G.M., Smith J.D. (1990) The relationship between situational stress and phantom limb pain: cross-lagged correlational data from six month pain logs. Journal of psychosomatic research. Available from: <https://www.ncbi.nlm.nih.gov/pubmed/2313614&gt; [Accessed 26 October 2020]

Bennington-Castro, J. (2013) Sensing your own body is more complicated than you realize. Available from: <https://io9.gizmodo.com/sensing-your-own-body-is-more-complicated-than-you-real-1473461740&gt; [Accessed 26 October 2020]

Marguč, K. (2010) Colors: From Dispositionalism to Subjectivism. Available from: <http://www.etd.ceu.hu/2010/marguc_karmen.pdf&gt; Page 45. [Accessed 26 October 2020]

Melzack R. & Wall P. D. (1965) Pain Mechanisms: A New Theory. Science. 150(3699). 971- 979. Available from: https://www.canonsociaalwerk.eu/1846_anesthesie/Canon%20Palliatieve%20Zorg%20-%20Ontstaan%20van%20anesthesie%20-%20Science%20-%20melzackandwallgatecontroltheory.pdf [Accessed 26 October 2020]

Perur, S. (2014). The man who treats “phantom” pain… with mirrors. Mosaic. Available from: <http://www.bbc.com/future/story/20140708-the-man-who-treatsphantom-pain&gt; [Accessed 26 October 2020]

Physical Medicine and Rehabilitation Clinic., (1995) U.S. Protocol for Filipino Physical Therapists. Rex Book Store, Inc. First edition. Page 473.

Shukla G. D. et al. (1982) A psychiatric study of amputees. British Journal of Psychiatry. 141:50-3. Available from: doi: 10.1192/bjp.141.1.50

Tobin, A. (2014). Solved: Mystery of Phantom Limb Pain. Haaretz. Available from:<https://www.haaretz.com/science-and-health/solved-mystery-of-phantom-limbs-1.5249939&gt; [Accessed 26 October 2020]

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