Phantom pain is a painful perception that an individual experiences relating to a limb or an organ that is not physically part of the body, either because it was removed or was never there in the first place.

Sensations are reported most frequently following the amputation of a limb, but may also occur following the removal of a breast, tongue, or internal organ. Phantom eye syndrome can occur after eye loss. The pain sensation and its duration and frequency varies from individual to individual.

Phantom pain should be distinguished from other conditions that may present similarly, such as phantom limb sensation and residual limb pain.

Phantom limb sensation

Phantom limb sensation is any sensory phenomenon, except pain, which is felt at an absent limb or a portion of the limb. It is estimated that up to 80% of amputees experience phantom limb sensations at some time of their lives. Some experience some level of this phantom feeling in the missing limb for the rest of their lives.

Residual limb pain

Residual limb pain, also referred to as stump pain, is a painful perception that originates from the residual limb, or stump, itself. Although these are different clinical conditions, individuals with phantom pain are more likely to concomitantly experience residual limb pain as well.

Signs and symptoms

The symptomatic course of phantom pain is widely variable, but the onset often presents within the first week after amputation. The duration of symptoms varies among individuals, with some reporting decreased pain over time and others reporting a more stable or even increasing trajectory. Sensations may be described as shooting, stabbing, squeezing, throbbing, tingling, or burning, and sometimes feels as if the phantom part is being forced into an uncomfortable position.

thumb|Visual representation of body parts within the somatosensory cortex

While the sensation often affects the part of the limb farthest from the body, such as the fingers or toes, other body parts closer to the brain, such as the arm or leg, can still experience similar sensations. It is thought that phantom pain more commonly involves the part of the limb farthest from the body because of its larger cortical representation within the somatosensory cortex.

Triggers

Overall, the sensations may be triggered by pressure on the remaining part of the limb, emotional stress, or changes in temperature.

Causes

Individuals may experience phantom pain following surgical or traumatic amputation of a limb, removal of an organ, or in instances of congenital limb deficiency. It is most commonly observed after amputation, although less frequent cases have been reported following the removal of a breast, tongue, or eye.

Pathophysiology

The neurological basis and mechanisms for phantom pain are all derived from experimental theories and observations. Little is known about the true mechanisms causing phantom pain, and many theories highly overlap.

Historically, phantom pains were thought to originate from neuromas located at the stump tip. This finding suggests that there is also a central mechanism responsible for generating painful sensations.

Currently, theories are based on altered neurological pathways and maladaptive changes within the peripheral nervous system, spinal cord, and brain.

Peripheral mechanisms

Neuromas formed from injured nerve endings at the stump site show increased sodium channel expression and are able to spontaneously fire abnormal action potentials. This increased activity of Aδ and C fibers, which are involved in pain and temperature sensation, can contribute to phantom pain. However, it has been noted that pain still persists once the neuromas have ceased firing action potentials or when peripheral nerves are treated with conduction blocking agents. However, because patients with complete spinal cord injury have experienced phantom pain, there must also be an underlying central mechanism within the brain.

Central mechanisms

Under ordinary circumstances, the genetically determined circuitry in the brain remains largely stable throughout life. For much of the twentieth century, it was believed that no new neural circuits could be formed in the adult mammalian brain, but experiments from the 1980s onward cast this into doubt. After amputation, cortical remapping is the process by which areas of the somatosensory and primary motor cortices representing the lost limb are invaded by nearby regions. This allows areas of the brain formerly receiving input from the lost limb to be stimulated from the nearby invading cortical regions.

Most of the studies using functional MRI to investigate cortical remapping in humans have been in upper limb amputees. Following the loss of an arm, the majority of motor reorganization occurred as a downward shift of the hand area of the cortex onto the area of face representation, especially the lips.

The neuromatrix

The neuromatrix theory, initially coined by psychologist Ronald Melzack in the 1990s, proposes that there is an extensive network connecting the thalamus and the cortex, and the cortex and the limbic system. The network is genetically predetermined, and is modified throughout one's lifetime by various sensory inputs to create a neurosignature. It is the neurosignature of a specific body part that determines how it is consciously perceived.

Support for the neuromatrix theory is largely from studies where cordotomy, and therefore elimination of pain signals transmitted to the brain, fail to treat phantom pains. Opposition to the theory exists largely because it fails to explain why relief from phantom sensations rarely eliminates phantom pains. It also does not address how sensations can spontaneously end and how some amputees do not experience phantom sensations at all. Doctors may prescribe medications, and some antidepressants or antiepileptics have been shown to have a beneficial effect on reducing phantom limb pain.

There are many different treatment options for phantom limb pain that are actively being researched. Most treatments do not take into account the mechanisms underlying phantom pains, and are therefore difficult to investigate. However, there are a few treatment options that have been shown to alleviate pain in some patients, but these treatment options usually have a success rate of less than 30%. However, there are currently no high-quality randomized trials supporting the efficacy of these medications. Tricyclic antidepressants, such as amitriptyline, are often used to relieve chronic pain, and recently have been used in an attempt to reduce phantom pains. Recent studies using amitriptyline have also failed to provide conclusive, non-conflicting results. N-methyl-D-aspartate (NMDA) receptor antagonists, such as ketamine, are thought to work by reversing the process of central sensitization within the spinal cord, which has been proposed as a possible mechanism for the development of phantom pain. Pain relief may also be achieved through use of opioids, calcitonin, and lidocaine. This theory proposes that the phantom limb feels paralyzed because there is no feedback from the phantom back to the brain to inform it otherwise. Ramachandran believes that if the brain received visual feedback that the phantom limb had moved, then the phantom limb would become unparalyzed. The study goes on to say that while the exact mechanism of mirror therapy isn't completely understood, it is a safe and inexpensive option for patients to consider. Out of 115 publications between 2012 and 2017 that investigated the use of mirror therapy for phantom pain, a 2018 review found only 15 studies whose scientific results should be considered. From these 15 studies, the reviewers concluded that mirror therapy is an effective tool to reduce both the duration and intensity of phantom pain.

Current theories on how mirror therapy may reduce phantom pain have largely come from studies investigating changes in the brain using functional MRI. There is evidence to show a reduction and reversal of cortical reorganization within the somatosensory cortex following mirror therapy. Since maladaptive changes within cortical regions of the brain are proposed to be a central mechanism of phantom pain, a reversal of this remapping is thought to alleviate pain.

Graded motor imagery

Graded motor imagery was initially developed to help patients suffering from complex regional pain syndrome, but has since expanded to other chronic pain conditions, including phantom pain. The treatment is thought to work in a similar fashion as mirror box therapy, where maladaptive cortical reorganization is reversed and there is no longer a functional connection between movement and pain. A recent systematic review and meta-analysis provided support for the use of graded motor imagery to help reduce the severity of phantom pain in amputees.

Motor execution with biofeedback

Phantom motor execution with biofeedback is a newer therapeutic intervention that takes advantage of augmented and virtual reality. During these sessions, patients wear virtual reality goggles that allow them to visualize their phantom limb as a normal, intact limb. They are then able to participate in different interactive games, such as reaching for and grasping objects. It is theorized that by doing so, there becomes a 'match' between the visual and somatosensory systems, which may lead to decreased phantom pain. Importantly, as opposed to conventional mirror box therapy, the ability to interact with virtual reality games may increase patients' participation and result in improved outcomes.

Deep brain stimulation

thumb|Deep brain stimulation for the management of phantom pain

Deep brain stimulation is a surgical technique used to alleviate patients from phantom limb pain. It is typically reserved for refractory cases or when all other therapeutic interventions have not provided relief. Prior to surgery, patients undergo functional brain imaging techniques such as PET scans and functional MRI to determine an appropriate trajectory of where pain is originating. Surgery is then carried out under local anesthetic, because patient feedback during the operation is needed. In the study conducted by Bittar et al., a radiofrequency electrode with four contact points was placed on the brain. Once the electrode was in place, the contact locations were altered slightly according to where the patient felt the greatest relief from pain. Once the location of maximal relief was determined, the electrode was implanted and secured to the skull. After the primary surgery, a secondary surgery under general anesthesia was conducted. A subcutaneous pulse generator was implanted into a pectoral pocket below the clavicle to stimulate the electrode. A recent systematic review found mixed results, also suggesting the need for additional randomized, controlled studies.

More than half the people that experience phantom pain would also experience residual limb pain.

History

The term "phantom limb" was first coined by American neurologist Silas Weir Mitchell in 1871. Mitchell described that "thousands of spirit limbs were haunting as many good soldiers, every now and then tormenting them". However, in 1551, French military surgeon Ambroise Paré recorded the first documentation of phantom limb pain when he reported that "the patients, long after the amputation is made, say that they still feel pain in the amputated part".