Introduction

People who have had limbs amputated often experience sensations that their extremities are still in place. These sensations are collectively termed phantom limbs, and have been described in literature since the 1500's. Ambroise Paré, a 16^th century military surgeon, described how patients felt pain long after amputations, and Herman Melville even mentions phantom limb sensations in his acclaimed novel Moby Dick, published in 1851.

Physicians used to discard these sensations as either metaphysical or purely psychological. Silas Weir Mitchell gave the first modern medical report of phantom limb in 1871. He referred to the phenomenon as a sensory "ghost" that initiated after amputations. These sensations were also described as hallucinations and disturbances of the body image (5).

Phantom limb sensations are now viewed as real, physiological events, and consideration for treatment is directed more at the body's neurological response. The sensations that cause the most distress and are the most clinically significant are those resulting in pain. Phantom limb pain (PLP) is experienced by as many as 90% of patients with phantom sensations (12). Researchers have not been able to postulate a universally-accepted mechanism for phantom limbs, making this an intriguing subject for medical research.

Phantom limb sensations are reported by 70-100% of amputees (8,9). The sensations are neither gender- nor age-biased (9,11) and can occur after amputations (2,3,6), spinal cord injuries, and the removal of some internal organs (i.e. the bladder) (12). Patients have reported phantom tingling (2,3), numbness, itching (9), warmth, wetness, relief of pressure (such as emptying the bladder), and even phantom visual and auditory sensations (12). The most common PLP are described as burning, cramping, squeezing, pins and needles (9), throbbing (12), stabbing, and shocking (6). With the exception of pain, phantom limb sensations seldom distress the amputee (6). The amputee may actually welcome the sensations of phantom limb since they enable precise movement of a prosthesis. (2,6)

One third of phantom limb patients experience the phenomenon of telescoping (9), where the amputee has a sensation that the phantom limb is gradually shrinking. Some amputees even report that the phantom limb end (foot or hand) feels directly attached to the stump (2,3,9). Some amputees have reported experiencing the phantom limb remaining in awkward positions. The phantom limb may also protrude straight out from the stump, as in an amputation at the shoulder where the phantom arm protrudes laterally. Some amputees have reported that their limbs are oriented as if they were broken, resulting in the feeling of a permanent cramp and causing great distress to the individual (12). Others report that they perceive muscular fatigue and aching upon moving the limb (8).

The History of Proposed Mechanisms

Hypotheses pertaining to phantom limb mechanisms have gone through much debate. The fundamental problem for deciphering the mechanism is determining its location. Research has shown that both the central nervous system (CNS) and the peripheral nervous system (PNS) play roles in the phantom limb response (2,7), with the CNS being the most important contributor (12).

The sensory end of a neuron, once activated, generates an impulse that travels to the central nervous system and the brain, where the impulse is converted into the sensation that we perceive. In a severed limb, the cut neurons grow into nodules of disordered nervous tissue, called neuromas. The oldest proposed mechanism for phantom limbs states that these nodules continue to generate impulses to the spinal cord and the brain as if the limb were still attached (8).

Evidence to support this mechanism was gathered in the 1970's, when neuromas generating spontaneous electrical activity were documented (11). They were also noted as being highly sensitive to mechanical and electrical stimuli, and surgical removal of neuromas was found to provide some relief (6).

Several observations remain unexplained. Phantom sensations continue to occur in the absence of stimulation to the stump, after removal of the neuromas, in the absence of nerve damage, and with complete transection of the spinal cord (thereby blocking the periphery signal). Moreover, it has been observed that the sensations can be present immediately after amputation, which is prior to the formation of neuromas (6).

Later researchers proposed that PLP could be caused by disinhibition of spinal cord neurons that have lost sensory impulse. This hypothesis proposes that when neurons lose their sensory impulses they spontaneously begin firing excessive impulses to the brain. These abnormal impulses are perceived as pain when they enter the brain. The hypothesis, while supported by evidence that high levels of electrical activity are spontaneously generated by severed sensory neurons, was abandoned when it was discovered that paraplegics felt limb pain even with a complete break in the cervical region of the spinal cord (8).

Melzack made a significant contribution to the modern hypotheses in 1989 with his proposal that phantom sensations are derived from a part of the brain he called the "neuromatrix." According to Melzack, the "neuromatrix" is a network of neurons that generates a continuous pattern of impulses unique to every individual. These impulses do not operate based on sensory input as in the neuroma hypotheses, rather the impulses are initiated in the so-called "neuromatrix." In addition, the impulses arise from an area in the brain, as opposed to the spinal cord. These two aspects allow for the sensations to be felt 1) in the absence of sensory input and 2) in the presence of any disruptions (potential blocks in the signal) from the brain stem to the periphery (8).

Melzack suggested that in order for phantom limb to have such a broad range of sensations, the matrix must be diffusely located, including at least three neural circuits that connect the cerebral cortex: the thalamus, the brain stem, and the limbic system. Moreover, using evidence that patients born without limbs often experience phantom sensations, Melzack suggested that the matrix is present before birth and held within an individual's genes. He stated that the body normally uses this circuitry as a means of understanding one's self-being (8).

Canavero argued against the "neuromatrix" hypothesis using evidence that focal brain lesions fail to consistently relieve phantom pain. He believes that there may be a reverberation loop of brain processes between the thalamus and the cerebral cortex. This hypothesis suggests that lesions in the corticothalamic area of the brain may have an immediate effect in terminating the pain (2).

The relief of phantom sensations seldom alleviates phantom pain, indicating that they might be involved in separate mechanisms. Thus, researchers have tried to find an explanation for PLP that would not affect general phantom sensations. Davis cited two prominent hypotheses: 1) an initial peripheral response to a cut sensory nerve causes a cascade of events leading to the generation of spontaneous pain sensations initiated by the CNS; and 2) the changes in the peripheral nerves permanently alter the sections of the neurons entering the dorsal horn of the spinal cord. This alteration causes inhibitory interneurons to die, thereby permitting an enhanced pain transmission (3).

Discussion

The mechanism of PLP has been elusive. While the contributions by Melzack, Canavero, and others have scientific basis, there remains no definitive explanation.

Currently, most believe that PLP originates in the brain with limited contributing mechanisms from the periphery (2,6,10); however, the exact origin of PLP is difficult to pinpoint. The mainstream hypotheses propose origins that cover many areas of the brain; therefore, one particular component of the brain cannot be isolated for study (6). Baron and Maier were able to find experimental evidence that PLP originates in the brain or the brain stem by studying nociceptive pathways and brain stem infarctions (1). Additional support for a cerebral origin comes from evidence that a normal sensation can be initiated in the absence of external stimuli (3).

The fact that the sensations are extremely real to the patient supports the "neuromatrix" hypothesis of Melzack. His proposed mechanism presumes that the sensations occur through a normal, unchanged pathway. Many of the other hypotheses rely on an alteration of the neural network in some way. It is argued that an abnormal pathway would lead to an abnormal sensation, not a similar or enhanced sensation (9).

Many argue that while Melzack's hypothesis is promising for phantom sensations, it does not adequately explain PLP or why relief of phantom sensations seldom alleviates phantom pain. The subsequent hypotheses by Canavero and those cited by Davis are considered more tenable for PLP but have not been proven (2,3). The current hypotheses fail to explain why the sensations can spontaneously cease or why some amputees do not experience PLP (6). Studies have found, however, that PLP can spontaneously cease when the area of origin learns to stop association with inappropriate stimuli (4).

There is need for further research into this fascinating condition. Surgeons have attempted several procedures to alleviate PLP, mainly involving the removal of the neuroma or a section of the CNS. Treatment has also included acupuncture, electrical shock, vibration, electrical nerve stimulation, ultrasound, psychological intervention, and analgesic medications. These attempts, however, have not offered meaningful or long-term improvement of PLP (3). Providing adequate treatment for PLP depends largely on determining its mechanism, a task likely to be bequeathed to the young scientists of today.