Phantom limb pain (PLP) refers to the pain experienced by a body part that does not exist. It is usually described as tingling, itching, and pain. It occurs in amputees, as well as people who were born without a body part. Currently, there is no cure for PLP as the underlying mechanism is still unclear. However, there has been research investigating different ways to reduce PLP.

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Introduction

Definition of phantom limb pain (PLP)

Phantom limb pain is pain felt in a body part that no longer exists, including amputated body parts and congenital absence of limbs.¹ The concept was first introduced by Ambrose Pare, a French military surgeon, in the 16th century and coined by Silas Weir Mitchell, a Civil War surgeon in the 19th century.^2,3 The nature of the pain can vary, in intensity, location, frequency, and duration.⁴

Usually, people experience phantom limb pain in missing arms and legs. However, some may also experience it in their breast, rectum, penis, testicles, eyes, tongue, and teeth. The pain is often triggered by salient events, thoughts, and feelings.⁴ It is still a poorly understood phenomenon without a cure. 

Prevalence and significance of PLP

It occurs in around 80% of all amputees and people can still experience PLP more than 25 years after amputation.⁵ It has been reported to be more common for those assigned female at birth (AFAB) to experience PLP than those assigned male at birth (AMAB).⁶ Recent studies have revealed that it is more common to experience PLP in upper limb amputations than in lower limb amputations.⁷ However, more investigation is needed to confirm the influence of sex and amputation of different body parts on PLP. 

Although phantom pain is reported in amputated body parts like teeth, tongue, and breast, it is most common in amputated limbs.⁸ It is also reported that people expressing depressive symptoms are more likely to describe their pain as more intense than those without depressive symptoms, suggesting that emotions may contribute to more persistent PLP.⁹

Symptoms of phantom limb pain

Common sensations associated with PLP include:¹⁰

• Pain
• Itching
• Burning
• Tingling

Mechanisms of phantom limb pain

Peripheral mechanism

When a person undergoes amputation, the peripheral nerves of the affected body part are severely damaged. The damage to tissue and neurons disrupts the afferent pathway. The afferent pathway describes nerve cells that carry sensory information from sensory receptor cells towards the central nervous system. This damage leads to deafferentation which is defined as a loss of sensory input, in this case from the amputated body part. The nerve endings in that body part may form neuromas which can cause spontaneous and painful signals.¹¹

During this process, there will be hyperexcitation and neurons will spontaneously discharge. This abnormal hyper-excitatory activity in the peripheral nervous system is suggested to be a possible cause of the phantom pain. However, it cannot explain why people born without a limb can also experience phantom limb pain.

Central neural mechanisms

Cortical remapping, or cortical reorganisation, is the most discussed mechanism for the development of PLP. Cortical remapping can be thought of as a reorganisation of the brain, the areas of the brain that were responsible for the amputated body part are taken over by adjacent areas of the brain, affecting senses like touch and pain. With greater extents of cortical reorganisation, there may be higher degrees of pain, and this is associated with larger areas of deafferentation.

Psychogenic mechanism

Although there have not been studies supporting the psychogenic mechanism of PLP, feeling stressed, anxious, exhausted, and depressed are suggested to exacerbate PLP. It has been found that personality traits such as passive coping styles, and catastrophizing behaviours are associated with the development of PLP regardless of whether they have depression or anxiety.¹² 

Treating phantom limb pain

Although there is no cure for PLP, there are different medication-based and non-pharmaceutical approaches to treating PLP.¹⁰ The following are some of the treatments that have been proposed to reduce PLP. 

Medication-based approaches

Non-steroid anti-inflammatory drugs (NSAIDs) and Paracetamol

NSAIDs and paracetamol are the most commonly used treatments for PLP. 

Opioids

Opioids like tapentadol have proved to be effective in treating neuropathic pain and PLP through observational and randomised controlled trials. However, opioids should be used alongside antidepressants or neural-modulating agents such as gabapentin and pregabalin. It is also important to be careful with using opioids to avoid tolerance and dependence on the drug as they can be highly addictive.

Antidepressants

Antidepressants are commonly used to treat PLP. Relative to other antidepressants, Amitriptyline is suggested to be the most effective at reducing PLP. Other antidepressants such as nortriptyline, desipramine, and duloxetine have also been demonstrated to be effective in reducing PLP.

Anticonvulsants 

Anticonvulsants like gabapentin and pregabalin have shown mixed results. Studies have shown the effect of gabapentin is not always consistent and helpful in treating PLP. However, gabapentin has shown better results than placebos. 

N-methyl-d-aspartate (NMDA) receptor antagonist 

The mechanism of the NMDA receptor antagonist is not clear. Ketamine and dextromethorphan are the two drugs that are primarily used to treat pain syndromes.

Topical analgesics 

Topical analgesics like Capsaicin have been demonstrated to be effective in reducing PLP and hypersensitivity. However, more evidence is needed to draw a conclusion on its effectiveness.

Botulinum toxin type B injections 

Botulinum toxin type B injections are used to treat hyperhidrosis where post-amputation patients experience excessive sweating near their amputated body part. Excessive sweating near the amputated part hinders the use of a prosthetic. Botulinum toxin type B injections treating hyperhidrosis have shown positive outcomes in reducing PLP and sweating.

Local anaesthetics

Anaesthetics such as bupivacaine have been shown to improve pain relief in PLP randomised trials. 

Non-pharmacological treatments

Transcutaneous electrical nerve stimulation (TENS)

TENS has been demonstrated to be effective in treating PLP, especially low-frequency and high-frequency TENS. 

Mirror therapy

Mirror therapy is thought to reduce PLP by the restoration of normal somatosensory and visual inputs to the brain.¹³ Studies have shown people with lower limb phantom limb pain experience a decreased intensity in pain after mirror therapy. 

Spinal cord stimulation (SCS) 

Spinal cord stimulation is an effective treatment for PLP, it works by implanting a device that stimulates transdural dorsal columns of the spinal cord. 

Other neuromodulation approaches 

Peripheral nerve stimulation (PNS) can also help reduce PLP.

Recent Advances in phantom limb pain research

Targeted muscle reinnervation (TMR)

TMR involves re-routing and coapting the distal part of a transected (damaged) nerve to a motor nerve that is controlling a nearby muscle through surgery. As time goes by, the coapted transected nerve will join the motor nerve and become one new nerve that reinnervates (restores nerve function to) the muscle. 

This technique is suggested to restore continuity and function physiologically, prevent the formation of neuromas, and benefit the cortical reorganisation process.^14,15,16 As the efficacy of TMR in reducing PLP is not clear, further research is needed. 

Repetitive transcranial magnetic stimulation (rTMS)

One of the suggested underlying mechanisms of PLP is cortical remapping. The imagined movement of the phantom limb activates the brain region responsible for the phantom limb and its adjacent body part. It has been found that the greater the extent the brain is remapped, the greater the degree of PLP is experienced.¹⁷

rTMS is suggested to be conducive to the prevention of cortical remapping in the sensorimotor regions, thus reducing PLP.¹⁸ rTMS targets the somatosensory and motor cortex by emitting a magnetic pulse. It is suggested to activate the inhibitory pathways and hence reduce PLP.

Imaginal phantom limb exercise

It is proposed that cortical remapping is caused by mental imagery, including imagining movements of the phantom limb deliberately. It is assumed that imaginary movements of the phantom limb activates the brain networks which would be responsible for the movement of the limb were it still present. 

However, the evidence from studies investigating the effectiveness of imaginal phantom limb exercises is not strong enough to draw a conclusion. Further research is needed with larger sample sizes and better experimental designs. 

Virtual and augmented reality

Virtual reality allows people to immerse themselves in a virtual world whereas augmented reality involves the addition of digital elements to the actual world. These interventions are said to be an advanced version of mirror therapy as they allow individuals to move their limbs independently while seeing their phantom limb interacting with the surroundings. However, further research is needed to investigate its efficacy in reducing PLP.

Eye movement desensitisation and reprocessing (EMDR) therapy

EMDR targets the psychological mechanisms underlying PLP, like painful and traumatic memories. It reduces PLP by processing the painful memories causing PLP on an emotional level. Further research is needed to determine its effectiveness in reducing PLP.

Summary

All in all, phantom limb pain is the pain that people suffer from a body part that does not exist. Although the underlying mechanism is unclear, there are medications and therapies that are suggested to be effective in treating PLP. The three suggested mechanisms are the peripheral mechanism, the central mechanism, and the psychogenic mechanism. As there is more and more ongoing research regarding PLP, the underlying mechanisms will continue to be better understood and new treatments and therapies may emerge.