Phantom Limb Pain

Phantom-limb pain is a common sequela of amputation, occurring in up to 80% of people who undergo the procedure. It must be differentiated from non-painful phantom phenomena, residual-limb pain, and non-painful residual-limb phenomena. Central changes seem to be a major determinant of phantom-limb pain; however, peripheral and psychological factors may contribute to it.

The amputation of a limb is commonly followed by the sensation that the deafferented body part is still present. These non-painful phantom sensations may include a specific position, shape, or movement of the phantom, feelings of warmth or cold, itching, tingling, or electric sensations, and other paraesthesias.

Pain in the body part that is no longer present occurs in 50–80% of all amputees. The term phantom-limb pain was coined by Mitchell in 1872. Ambroise Paré had postulated in 1552 that peripheral factors as well as a central pain memory might be causing phantom-limb pain and was the first to describe the phenomenon.

Procedures we offer for Phantom Limb Pain

AETIOLOGY OF PHANTOM-LIMB PAIN

Both peripheral and central factors have been described as determinants of phantom-limb pain. Psychological factors do not seem to contribute to the causation but may instead affect the course and the severity of the pain.

Central factors

Increased activity of peripheral nociceptors leads to a permanent change in the synaptic structure of the dorsal horn in the spinal cord, a process called central sensitisation. This process is characterised by increased excitability of the dorsal-horn neurons, reduction of inhibitory processes, and structural changes at the central nerve endings of the primary sensory neurons, the interneurons, and the projection neurons. This central sensitisation is mediated by the NMDA receptor and its transmitter glutamate. Possible mechanisms are that low threshold afferents become functionally connected to ascending spinal projection neurons that carry nociceptive information, or inhibitory interneurons may be destroyed by rapid discharge from injured tissue leading to a hyperexcitable spinal cord.

Peripheral-nerve injury can lead to degeneration of C-fibre terminals in lamina II, which may induce sprouting of A-fibre terminals into this area, where they are normally not represented (they normally terminate in laminae III and IV). The incoming A-fibre input might then be interpreted as noxious and could be the anatomical substrate of allodynia.

A mechanism of special relevance to phantom phenomena may be the invasion of regions of the spinal cord where the deafferented limb was previously represented. In nerve constriction injury, a commonly used animal model for neuropathic pain, expansion of receptive fields and a shift in activity from adjacent neurons into the deafferented zone have been observed. These processes may be due to unmasking of previously silent connections or the sprouting of new connections.

Peripheral factors

Peripheral changes, such as nociceptive input from the residual limb, have been viewed as an important determinant of phantom-limb pain. This idea is supported by the moderately high correlation between residual-limb and phantom-limb pain. Ectopic discharge from a stump neuroma has been postulated as one important peripheral mechanism. When peripheral nerves are cut or injured, regenerative sprouting of the injured axon occurs. In this process, a neuroma in the residual limb may be formed—ie, enlarged and disorganised endings of C fibres and demyelinated A fibres that show an increased rate of spontaneous activity.

A further site of ectopic discharge may be the dorsal root ganglion (DRG). Ectopia in the DRG can amplify discharge coming from the residual limb or can lead to crossexcitation and instigate the depolarisation of neighbouring neurons.

Psychological factors

There has been an assumption that phantom limbs and pain are related to unresolved grief over the loss of the limb and may be a psychosomatic manifestation of a premorbid personality. The idea that phantom-limb pain ‘is just in the head’ of the patient is still prevalent and may contribute to the large divergence in reported incidence and prevalence. Empirical studies on psychological characteristics of patients who have phantom-limb pain and controls show that these patients tend to have normal psychological profiles.

Phantom-limb pain is, however, triggered and exacerbated by psychological factors. Longitudinal diary studies showed that there is a significant relation between stress and the onset and exacerbation of episodes of phantom-limb pain, probably mediated by activity in the sympathetic nervous system and increases in muscle tension. Cognitive factors also play a part in the modulation of phantom-limb pain; patients who lack coping strategies and fear the worst when confronted with episodes of pain are more affected by the pain and report more interference than patients who cope well with their problem. Psychological variables before the amputation are also predictive of phantom-limb pain.

Clinical features

Phantom sensation

Phantom sensation and phantom pain commonly co-exist. Phantom sensation occurs in most amputees, and is experienced as resembling the pre-amputation limb in shape and size and may include feelings of posture and movement. Patients may describe feelings of warmth, cold, itching, tingling or electric sensations. Phantom sensation usually appears soon after amputation and can last from weeks to years, but is not experienced as being painful.

Telescoping

Some patients also describe the phenomenon of ‘telescoping’. This is where the distal part of the phantom limb is felt to be closer to the stump or within the stump itself. For example, forearm amputees may describe feeling that their amputated hand is attached to their elbow stump. This probably occurs because the cortical magnification of the hand is proportionally over represented on the somatosensory cortex.

Phantom pain

Around 60 – 80% of amputees will experience phantom pain in the early post-operative period with the incidence decreasing with time following amputation. The incidence of phantom limb pain appears to be independent of age, gender and level or side of amputation. 75% of patients will develop phantom pain within the first few days after amputation but the first emergence of phantom pain may be delayed and develop several years later. Phantom pain is often regarded as a chronic pain problem lasting for many years following amputation. Several studies, however, have shown a reduction in pain over periods of 2 – 5 years post amputation, although most continue to experience some pain beyond this.

A number of factors have been shown to be predictive of the onset of phantom limb pain post-operatively. Patients found to be most at risk are those who have severe pain in the amputated limb pre-operatively, patients undergoing bilateral amputation and patients with persisting stump pain. The incidence of phantom limb pain is however lower in paediatric amputees and very rare in those with congenitally absent limbs.

Phantom pain is most commonly thought of as occurring following amputation of a limb but it is also well recognised following amputation of other bodily parts including testis, penis, breast, eye or tongue. The incidence of phantom pain following mastectomy is quoted as high as 15% but is a poorly recognised and seldom acknowledged sequelae of this type of operation.

Phantom pain is usually felt as being located in the distal part of the amputated limb and is often described as being gripping, burning, shooting or cramping in character. Unlike many forms of neuropathic pain, phantom limb pain is commonly intermittent although some patients will experience constant pain. Once established, phantom limb pain can be very resistant to treatment; for instance dense regional anaesthetic blockade provides only limited benefit. Indeed, a number of cases have been reported of patients developing phantom limb pain for the first time while under spinal anaesthetic and also of patients experiencing exacerbations of pre-existing phantom pain with spinal and epidural anaesthesia. This reinforces the view that phantom limb pain is not solely a phenomenon of the peripheral nervous system but involves more widespread and complicated central processes.

Stump pain

Stump pain is common in the early post-operative period. This is an acute nociceptive pain that usually resolves as the wound heals. Stump pain may persist in 5 – 10% of patients due to on-going local pathology or an acute neuropathic process. Sensory examination of the stump at this time may demonstrate hyperalgesia and allodynia. Surgical revision should be avoided if at all possible and is only indicated for localised pathology such as osteomyelitis or abscess. Persistent stump pain may be a risk factor for phantom pain.

At a later stage, once the patient begins rehabilitation and mobilisation, stump pain may develop or be exacerbated due to a poorly fitting prosthesis.

Prevention of phantom limb pain

Many studies have been undertaken investigating methods of preventing phantom limb pain. A popular theory has been the use of pre-emptive analgesia. The constant, supra-normal nociceptive input from an amputated limb is thought to contribute to the neural re-organisation, which may lead to phantom pain phenomena. It was hoped that by initiating intensive pre-operative analgesia, particularly by afferent nerve blockade, abnormal neural re-organisation may be prevented. However, in patients who have experienced a period of severe pain pre-operatively these changes may have already taken place.

Much of the early work in this area examined the impact of prolonged pre-operative epidural analgesia on the incidence of phantom pain. Despite showing promising early results, it was later realised that some studies had significant methodological problems and subsequent larger studies found no significant benefit on the overall incidence of phantom pain with this technique. Pre-operative epidural anaesthesia may however decrease the incidence of severe phantom pain but not the overall incidence of phantom pain.

An alternative, and increasingly popular technique to prevent phantom pain involves the placement of peri-neural catheters either pre or intra-operatively. Administration of local anaesthetic at the time of amputation and as a continuous infusion for 72 hrs post operatively has been shown to be of some benefit in helping prevent phantom pain. The addition of clonidine to a peri-neural local anaesthetic infusion may confer an additional benefit.

Treatment of phantom limb pain

Anti-neuropathic drugs

Anti-neuropathic medications form the main stay of management in phantom limb pain. These drugs include:

  • Tricyclics
  • Gabapentinoids (Gabapentin, Pregabalin)
  • Selective noradrenaline reuptake inhibitors (SNRIs)

 Other drug treatment

  • NMDA receptor antagonists (ketamine intravenous)
  • Opioids
  • Calcitonin (acute phase only)

Non-pharmacological treatments

TENS

It is not clear where the optimum site for placement of TENS electrodes. One approach is to apply stimulation to the contralateral limb. There may also be benefit in placing electrodes on the chest wall or flank in patients who display clear somatotropic representation of the limb on these areas.

Acupuncture

Acupuncture may have a beneficial effect in some cases of stump and phantom limb pain.

Mirror therapy

The mirror box is a device containing a vertically placed mirror into which the amputated limb is placed and is positioned so that a reflection of the patient’s intact limb is ‘superimposed’ onto the perceived position of the phantom limb. It has been shown that mirrored movements activate the contralateral sensorimotor cortex, and this is associated with a reduction in pain.

The mirror box is particularly helpful in patients who experience spasms of their phantom upper limb perceived as involuntary clenching of the missing hand. The mirror box allows the patient to visualise the unclenching of this limb, which can help relieve the pain of these spasms.

Summary

Treatment of phantom pain is very difficult. Medical treatment should follow the guidelines for other neuropathic pain conditions. Since medical treatment may not always be successful, combinations of medical and nonmedical treatment should be tried. Alternative treatments should be considered if conventional treatment is inadequate.

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