phantom limb pain psyc

Psychological Factors Associated with Phantom Limb Pain: A Review of Recent Findings

Affiliations.

• 1 Biopsychology and Cognitive Neuroscience, Faculty of Psychology and Sports Science, Bielefeld University, Bielefeld, Germany.
• 2 Department of Cognitive and Clinical Neuroscience, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
• 3 Center for Neuroplasticity and Pain (CNAP), SMI®, Department of Health Science and Technology, Aalborg University, Aalborg, Denmark.
• PMID: 30057653
• PMCID: PMC6051014
• DOI: 10.1155/2018/5080123

Phantom limb pain (PLP) is a common phenomenon occurring after the amputation of a limb and can be accompanied by serious suffering. Psychological factors have been shown to play an important role in other types of chronic pain, where they are pivotal in the acquisition and maintenance of pain symptoms. For PLP, however, the interaction between pain and psychological variables is less well documented. In this review, we summarize research on the role of emotional, motivational, cognitive, and perceptual factors in PLP. The reported findings indicate that emotional factors modulate PLP but might be less important compared to other types of chronic pain. Additional factors such as the amount of disability and adjustment to the amputation appear to also play a role. Bidirectional relationships between stress and PLP have been shown quite consistently, and the potential of stress and tension reduction in PLP treatment could be further exploited. Little is known about the role of cognitive variables such as attention or expectation. Catastrophizing seems to aggravate PLP and could be targeted in treatment. Body perception is altered in PLP and poses a potential target for novel mechanistic treatments. More research on psychological factors and their interactions in PLP is needed.

Publication types

• Anxiety / etiology
• Catastrophization / psychology
• Depression / etiology
• Pain Measurement
• Perception / physiology
• Phantom Limb / physiopathology*
• Phantom Limb / psychology*

• Chronic Pain

Clearing the Brain of Phantom Pain

Mirror therapy can re-program a brain's malfunctioning pain system..

Posted May 31, 2012

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Mirror therapy in action

I have a vague memory of learning about the brain and pain in the early seventies when I was an undergraduate student. Pain gateways in the brain had something to do with our individual pain thresholds. Since then our understanding of pain has made giant leaps forward, and for the millions of people—about one in six in the population—who suffer from chronic pain, the findings of pain neuroscientists and the development of therapeutic applications based on their discoveries should provide some relief, both emotional and physical.

Justine’s story is not uncommon in the chronic pain world, but her therapy experience is both inspirational and informative. She is a 40-something woman whose left leg was amputated below the knee after a car accident crushed it when she was in her twenties. Although with a prosthesis she learned to walk again, she was plagued by terrible itching and painful cramps in her missing limb for more than 15 years. Her phantom limb took over her life. She was convinced that her marriage didn’t survive because of her obsession with finding out why she had these debilitating cramps when others in the same situation did not. She decided her marriage breakup was for the best, as children were definitely out for her; she could never look after them while suffering this much agony, or alternatively being drugged to the eyeballs with pain medication . For years she managed to hold down a job as an office assistant, but only because she had a sympathetic boss who overlooked her frequent days off. But when she was 38, she resigned, no longer able to pretend that she could cope. After a year of social isolation and depression , she read an article in the local paper about a pain clinic that performed wonders for victims of chronic pain. She didn’t believe it could help her, but by now she would give anything a try. If she didn’t, she feared that her belief that suicide was a sin would forsake her. “Those therapists in the pain clinic literally saved my life,” she told me.

After very thorough physical, psychological and medical assessments, Justine was given her schedule. Five days a week she attended the clinic, moving through three types of therapy: cognitive behavior therapy, graded motor imagery, and mirror therapy. She began with cognitive behavior therapy where she unpacked her beliefs—the main one simply I can’t bear these painful cramps any longer— and learned how to re-program her thoughts, and in time her beliefs, to more positive and constructive ones. My cramps are bearable; I can get rid of this pain because it is in my brain, not in my missing leg; I can re-program my brain.

The psychologist also helped her understand how the brain fooled her into thinking her crushed leg was still there. Pain, she explained, results from damaging tissue and nerves, but you experience it via your brain. If you’re unconscious you can’t feel pain, however badly your body is burned or crushed. When you suffer an injury—for example, if you burn your hand on the iron—the pain sensors in your hand fire signals up your spinal cord and alert your brain. If this didn’t happen you might not pull your hand off the iron and rush to the sink to run cold water over your hand. But the brain doesn’t respond simply on autopilot. It constructs how you feel your pain based on your past experiences and beliefs, and even your genetics , as well as on the actual physical pain sensation from your hand. If you expect your hand to still be on fire after 10 minutes of cold water, it likely will be; your brain will keep the pain volume turned up. If you have been burnt before and know it will sting for a while but is no big deal, your brain will turn down the pain. It’s a sort of placebo effect , little different from when a mother tells her child that she will kiss the grazed knee better, and the child’s tears dry instantly and she runs happily back to play.

When pain continues after the body is healed, or as in Justine’s case, when the painful body part no longer exists, it is a sign that the brain’s central pain system has gone into overdrive. It hasn’t realized that a warning that your body is damaged or sick, and needs to be protected so it can heal, is no longer needed. This may be the culprit in a myriad of conditions when the pain is out of proportion to the physical problem or disease. Irritable bowel syndrome, chronic back pain, fibromyalgia , stress headaches, mild arthritis which should entitle the person to mild pain only… the list goes on. The owners of these pain-filled lives are not making it up, exaggerating, or being wimps. They really are in pain, but its ferocity comes largely from their mind, not their body.

It has been shown that some of our characteristic behaviors, even our personality , can play a role in priming our brain for pain. If you are an anxious sort of person, if you tend to look at everything as a catastrophe waiting to happen and obsess over everything that could go wrong, if you are depressed or are a pessimist , this can change the way your brain processes physical damage to your body, amplifying the pain signals.

Justine listened intently to all this, and it made a lot of sense for a grazed knee or a superficial burn, or even as an explanation for chronic pain from a bad back, but what about painful cramps in a leg that wasn’t even there?

Vilayanur Ramachandran’s fascinating research on phantom limbs has been the basis for much of our knowledge in this area. How can we feel a limb that we can see isn’t there; how can we scratch away that interminable itch, or dull that shooting pain in an absent leg with a drug designed to work on the physical body? When a limb is amputated, it is thought that the nerve cells in the somatosensory area of the cortex of the brain undergo substantial reorganization, sometimes resulting in mixed signals and fooling the brain into thinking the limb is still there. Before her leg was amputated Justine had suffered severe and appropriate physically-generated pain, and as a result, her brain assigned more nerve cells to the crushed leg, in order to protect it, using pain to warn Justine to treat her leg with care. Don’t knock it! This process where the brain map changes to assign more nerve cells to a damaged body part has been termed “smudging”, and essentially means that the body part gets bigger in the brain. The brain’s representation of a phantom limb becomes smudged, generating not only the sensation of the limb, but pain from the limb, even though the limb is no longer present.

Ramachandran came up with the idea of mirror therapy for phantom limb pain in the 1990s. Later, in 2009, Australian neuroscientists, Lorimer Moseley and Peter Brugger, incorporated it into graded motor imagery. Justine’s cramping pain in her phantom leg was so invasive that she no longer wanted to walk on her prosthesis, because this sometimes resulted in agonizing cramps in her missing foot and calf and into her stump. So the physical therapist began the next stage of her therapy by teaching her to imagine moving her left leg. First, all she had to do was watch a woman on a television screen walking and imagine it was her. We know that there are neurons in the brain that fire both when we imagine ourselves moving a specific body part and when we actually move that part. It is like rehearsing without the risk. Some athletes swear by it; they first visualize themselves performing perfectly—a perfect run down that ski slope, a perfect long jump, a faultless throw of the javelin—and then when they do the real action their brain is primed for the right moves, allowing the athlete to relax effortlessly into the right motions. (That’s the theory, anyway. I can tell you from my own experience on the ski slopes that it doesn’t work so well for amateurs!)

When Justine visualized herself as the woman walking on the television, it wasn’t painful. By doing this over and over, day after day, she re-programmed the neurons in her brain; almost as if the brain finally got the message that walking on her prosthesis and thus walking on her own phantom limb might not be painful either. After a lot of intensive imagery work, Justine began to walk again without the constant fear of painful cramps. But she still suffered cramps in her leg at times, often when she first got up in the morning, or when she was tired. Time to move onto mirror therapy.

The therapist sat her down with a long mirror placed between her bare legs, and facing towards her right side, the stump of her left leg hidden behind the mirror. Now she looked whole again. She ran her hand over her right leg and massaged her foot. In the mirror her left hand did the same to her left leg, and although she knew it was a reflection the sensation was spooky; it was as if her left leg had come back and felt normal, just like her right leg. The itch she had constantly in her left leg was relieved when she scratched her right leg, and when she smoothed soothing cream on her right leg, it soothed away the itch in her left leg as well. She began to experiment at home, whenever the cramps began, and found that by sitting with the mirror fooling her brain into thinking she had a left leg, she could turn off the cramps. The relief was so startling that it became part of her morning routine: a session with the mirror as soon as she got out of bed.

Six months later her phantom cramps had disappeared, and she no longer needed the mirror therapy. Along with the pain went the irritating itching, and without that she no longer felt her lower leg. What a relief that was. She loved that stump! She was soon weaned off the cocktail of pain relievers and antidepressants she’d been taking. Now all she had to contend with was the discomfort she sometimes felt from the pressure of the prosthesis on her stump, but that was normal, and a minor irritation after the years of agony she had suffered. Her brain map had been un-smudged, and her brain’s pain control center was back on track, telling her when her prosthesis was too tight, but no longer needing to tell her to protect that missing leg.

Mirror therapy is by no means a cure for everyone with phantom pain, and there is still controversy about its effectiveness. Even Moseley, the originator of the therapy, now has serious doubts about its effectiveness ( http://cdns.bodyinmind.org/wp-content/uploads/Moseley-et-al-2008-PAIN-t… .) New theories are emerging to explain phantom limbs, and as always in science, they will continue to be updated as neuroscience research techniques improve.

But for Justine, mirror therapy along with other therapies, a positive attitude, and a great deal of hard work proved effective. For more on this fascinating topic, read the latest case study published this year by McGeoch and Ramachandran, another case of the banishment of phantom pain using mirror therapy. (McGeoch, P., and Ramachandran, V., (2012), The appearance of new phantom fingers post-amputation in a phocomelus, Neurocase, 18 (2), 95-97.)

Jenni Ogden, Ph.D. , clinical neuropsychologist and author of Trouble in Mind, taught at the University of Auckland.

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Phantom Limb Pain: Mechanisms and Treatment Approaches

The vast amount of research over the past decades has significantly added to our knowledge of phantom limb pain. Multiple factors including site of amputation or presence of preamputation pain have been found to have a positive correlation with the development of phantom limb pain. The paradigms of proposed mechanisms have shifted over the past years from the psychogenic theory to peripheral and central neural changes involving cortical reorganization. More recently, the role of mirror neurons in the brain has been proposed in the generation of phantom pain. A wide variety of treatment approaches have been employed, but mechanism-based specific treatment guidelines are yet to evolve. Phantom limb pain is considered a neuropathic pain, and most treatment recommendations are based on recommendations for neuropathic pain syndromes. Mirror therapy, a relatively recently proposed therapy for phantom limb pain, has mixed results in randomized controlled trials. Most successful treatment outcomes include multidisciplinary measures. This paper attempts to review and summarize recent research relative to the proposed mechanisms of and treatments for phantom limb pain.

1. Introduction

The concept of phantom limb pain (PLP) as being the pain perceived by the region of the body no longer present was first described by Ambrose Pare, a sixteenth century French military surgeon [ 1 ]. Silas Weir Mitchell, a famous Civil War surgeon in the nineteenth century, coined the term “phantom limb pain” and provided a comprehensive description of this condition [ 2 ]. It continues to remain a poorly understood and difficult to treat medical condition. A recent study estimated that there were about 1.6 million people with limb loss in the USA in 2005 and this number was projected to increase by more than double to 3.6 million by the year 2050 [ 3 ]. Vascular problems, trauma, cancer, and congenital limb deficiency are among the common causes of limb loss. The number of traumatic amputations has also increased since the beginning of conflict in Iraq and Afghanistan [ 4 ]. The incidence of PLP has been reported to range from 42.2 to 78.8% in patients requiring amputation [ 5 – 8 ].

Stump pain is described as the pain in the residual portion of the amputated limb whereas phantom sensations are the nonpainful sensations experienced in the body part that no longer exists [ 6 , 7 ]. Superadded phantom sensations are touch and pressure-like sensations felt on the phantom limb from objects such as clothing [ 9 ]. Risk factor for PLP are shown in Table 1 . Recent studies report the prevalence of PLP to be more common among upper limb amputees than lower limb amputees. It was also reported to be more common among females than males [ 10 , 11 ]. A survey reported greater overall average pain intensity and interference in females than males and females endorsed significantly greater catastrophizing, use of certain pain-coping strategies, and beliefs related to several aspects of pain resulting in poor adjustment [ 12 ]. Larger population studies are needed for more definite establishment of the risks associated due to the site of involved limb or gender of the patient in development of PLP. Phantom sensations and pain have been reported following amputation of different body parts including the eyes, teeth, tongue, nose, breast, penis, bowel, and bladder but the most common occurrence is following limb amputation [ 4 ]. The phantom pain and sensation may have its onset immediately or years after the amputation. There are reports of two peak periods of onset, the first within a month and the second a year after amputation [ 7 ]. The prevalence is reported to decrease over time after amputation [ 10 , 11 ]. PLP has been reported in people with congenital absence of limbs [ 13 ]. Tingling, throbbing, piercing, and pins and needles sensations were among the most commonly described types of pain [ 13 ]. The rate of phantom pain or sensation was not reported to be higher in people with bilateral limb amputation than those with single limb amputation [ 14 ]. A significant association has been reported between the PLP and residual limb pain [ 15 ]. The presence of preamputation pain is also reported to increase the risks of developing PLP [ 16 ]. It is likely that stress, anxiety, depression, and other emotional triggers contribute to the persistence or exacerbation of PLP. A study has found that amputees with depressive symptoms were more likely to characterize their pain as more severe than those without depressive symptoms [ 17 ].

Risk factors for phantom limb pain.

2. Mechanisms

PLP was once thought to be primarily a psychiatric illness. With the accumulation of evidence from research over the past decades, the paradigm has shifted more towards changes at several levels of the neural axis, especially the cortex [ 18 ]. Peripheral mechanisms and central neural mechanisms are among the hypotheses that have gained consensus as proposed mechanisms over the recent years. Proposed mechanisms to explain phantom limb pain are shown in Table 2 . However none of these theoretical constructs appears to be able to explain the phenomenon of PLP independently and many experts believe that multiple mechanism are likely responsible.

Proposed theoretical mechanisms to explain phantom limb pain.

2.1. Peripheral Mechanism

During amputation, peripheral nerves are severed. This results in massive tissue and neuronal injury causing disruption of the normal pattern of afferent nerve input to the spinal cord. This is followed by a process called deafferentation and the proximal portion of the severed nerve sprouts to form neuromas [ 18 ]. There is an increased accumulation of molecules enhancing the expression of sodium channels in these neuromas that results in hype-excitability and spontaneous discharges [ 19 ]. This abnormal peripheral activity is thought to be a potential source of the stump pain, including phantom pain [ 18 ]. Studies reporting the reduction of phantom pain with drugs blocking the sodium channels lend further support to this theory [ 20 , 21 ]. However, this cannot explain the mechanism of PLP in patients with congenital absence of limbs [ 4 , 18 ].

2.2. Central Neural Mechanisms

2.2.1. changes at the level of spinal cord.

The axonal sprouts at the proximal section of the amputated peripheral nerve form connections with the neurons in the receptive field of the spinal cord. Some neurons in the areas of spinal cord that are not responsible for pain transmission also sprout into the Lamina II of the dorsal horn of the spinal cord which is the area involved in the transmission of nociceptive afferent inputs [ 18 , 19 ]. This is followed by increased neuronal activity, expansion of the neuronal receptive field, and hyperexcitability of other regions. This process is called central sensitization. During this process, there is also an increase in the activity at NMDA receptors mediated by neurotransmitters such as substance P, tachykinins, and neurokinins at the dorsal horn of the spinal cord [ 22 ]. This is followed by a phenomenon called the “windup phenomenon” in which there is an upregulation of those receptors in the area [ 22 ]. This process brings about a change in the firing pattern of the central nociceptive neurons. The target neurons at the spinal level for the descending inhibitory transmission from the supraspinal centers may be lost. There also may be a reduction in the local intersegmental inhibitory mechanisms at the level of the spinal cord, resulting in spinal disinhibition and nociceptive inputs reaching the supra spinal centers. This lack of afferent input and changes at the level of the spinal cord have been proposed to result in the generation of PLP [ 22 – 24 ].

2.2.2. Changes at the Level of the Brain

Cortical reorganization is perhaps the most cited reason for the cause of PLP in recent years. During reorganization, the cortical areas representing the amputated extremity are taken over by the neighboring representational zones in both the primary somatosensory and the motor cortex [ 18 , 25 , 26 ]. The process and extent of cortical reorganization have been studied in both animal and human models following amputation and deafferentation. Cortical reorganization partly explains why the afferent nociceptive stimulation of neurons within the stump or surrounding area produces the sensation in the missing limb [ 4 , 27 ]. The extent of cortical reorganization has been found to be directly related to the degree of pain and the size of the deafferentiated region. Multiple imaging studies have correlated greater extent of somatosensory cortex involvement with more intense phantom limb experience [ 4 , 28 – 30 ].

Another proposed mechanism of PLP is based on the “body schema” concept that was originally proposed by Head and Holmes in 1912. The body schema can be thought of as a template of the entire body in the brain and any change to the body, such as an amputation, results in the perception of a phantom limb [ 31 ]. A further expansion of the body schema concept is the “neuromatrix and neurosignature” hypothesis proposed by Ronald Melzack in 1989. The neuromatrix can be conceptualized as a network of neurons within the brain that integrates numerous inputs from various areas including somatosensory, limbic, visual, and thalamocortical components. It then results in an output pattern that evokes pain or other meaningful experiences. The term “neurosignature” was proposed by Melzack to refer to the patterns of activity generated within the brain that are continuously being updated based upon one's conscious awareness and perception of the body and self. The deprivation of various inputs from the limbs to the neuromatrix causes an abnormal neurosignature to be produced that results in the generation of PLP [ 32 – 34 ].The other hypothesis relative to the mechanism of PLP has been derived from the research into illusory perceptions. It has been shown that the parietal and frontal lobes are also involved besides the primary somatosensory cortex in the perception of the abnormal somatosensory phenomenon [ 35 ]. Painful sensations, such as PLP, may be related to the incongruence of motor intention and sensory feedback and a corresponding activation of the parietal and frontal brain areas [ 36 , 37 ].

2.3. Psychogenic Mechanism

The assumption that PLP is of psychogenic origin has not been supported in the recent literature even though stress, anxiety, exhaustion, and depression are believed to exacerbate PLP [ 38 ]. A cross-sectional study found that amputation in people with personality traits characterized by passive coping styles and catastrophizing behavior was found to be associated with the development of PLP independent of anxiety and depression [ 39 ]. Most research on the relationship between psychological symptoms and PLP has been retrospective and cross sectional rather than longitudinal and thus limited inferences can be derived from these studies.

3. Treatment

A number of different therapies relying on different principles have been proposed for the management of PLP as shown in Table 3 . However, specific treatment guidelines are yet to evolve and most successful measures employ multidisciplinary approaches in the management of pain and in rehabilitation [ 40 ].

Treatments for phantom limb pain.

Adapted from [ 4 , 41 ].

3.1. Pharmacological Approaches

3.1.1. preemptive analgesia and anesthesia.

Preemptive use of analgesics and anesthetics during the preoperative period is believed to prevent the noxious stimulus from the amputated site from triggering hyperplastic changes and central neural sensitization which may prevent the amplification of future impulses from the amputation site [ 42 ]. However, the results of the studies in this area have not been definitive. A recent study reported the decrease in PLP at six months following amputation when optimized epidural analgesia or intravenous patient controlled analgesia was started between 48 hours preoperatively and 48 hours postoperatively [ 20 ]. Prolonged postoperative perineural infusion of ropivacaine 0.5% was reported to prevent or reduce PLP and sensations after lower extremity amputation [ 21 ]. Ketamine, however, was not found to significantly reduce acute central sensitization or the incidence and severity of postamputation pain [ 43 ]. A randomized controlled double-blind trial comparing epidural infusions between a group receiving ketamine and bupivacaine and another receiving ketamine and saline following intrathecal or epidural anesthetic for surgery showed no significant difference between the two groups but much less pain at one year was reported in both groups compared to other comparable studies [ 44 ].

3.1.2. Acetaminophen and Nonsteroidal Anti-Inflammatory Drugs (NSAIDs)

A cross sectional study found that acetaminophen and NSAIDs were the most common medications used in the treatment of PLP [ 45 ]. The analgesic mechanism of acetaminophen is not clear but serotonergic and multiple other central nervous system pathways are likely to be involved [ 46 ]. NSAIDs inhibit the enzymes needed for the synthesis of prostaglandin and decrease the nociception peripherally and centrally [ 47 ].

3.1.3. Opioids

Opioids bind to the peripheral and central opioid receptors and provide analgesia without the loss of touch, proprioception, or consciousness. They may also diminish cortical reorganization and disrupt one of the proposed mechanisms of PLP [ 4 ]. Randomized controlled trials have demonstrated the effectiveness of opioids (oxycodone, methadone, morphine, and levorphanol) for the treatment of neuropathic pain including PLP. Comparative trials have also shown benefit with opioids when compared with tricyclic antidepressants and gabapentin though the opioids were associated with more frequent side effects [ 48 ]. The total amount of opioid required to achieve analgesia may be less when used together with other agents, such as tricyclic antidepressants or anticonvulsants, which also have use in neuropathic pain modulation. Tramadol, a weak opioid and a mixed serotonin-noradrenalin reuptake inhibitor, has also been used in the treatment of PLP [ 4 , 49 ].

3.1.4. Antidepressants

Tricyclic antidepressants are among the most commonly used medications for various neuropathic pains including PLP. The analgesic action of tricyclic antidepressant is attributed mainly to the inhibition of serotonin-norepinephrine uptake blockade, NMDA receptor antagonism, and sodium channel blockade [ 50 ]. The role of tricyclic antidepressants is well established in other neuropathic pain conditions, but the results are mixed relative to their role on PLP [ 51 ]. A recent study reported excellent and stable PLP control with an average dose of 55 mg of amitryptline, but there are others in which tricyclic antidepressants failed to effectively control the pain. [ 49 , 52 ]. Nortriptyline and desipramine have been found to be equally effective and with less side effects compared to amitriptyline [ 53 ]. A small case series demonstrated the effectiveness of mirtazapine, an alpha 2 receptor antagonist with fewer side effects than tricyclic antidepressants in the treatment of PLP [ 54 ]. There are case reports relative to the efficacy of duloxetine, a NE and serotonin receptor inhibitor, in the treatment of PLP [ 55 ]. Even though there may be a role for the use of SSRI and SNRI in the treatment of neuropathic pain, the evidence is very limited and further research is needed [ 56 ].

3.1.5. Anticonvulsants

Gabapentin has shown mixed results in the control of PLP with some studies showing positive results while others not showing efficacy [ 57 – 59 ]. Carbamazepine has been reported to reduce the brief stabbing and lancinating pain associated with PLP. Oxcarbazepine and pregabalin may also play a role in the treatment of PLP, but further studies are required [ 4 , 60 ].

3.1.6. Calcitonin

The mechanism of action of calcitonin in treatment of PLP is not clear. Studies relative to its therapeutic role have been mixed [ 61 , 62 ].

3.1.7. NMDA Receptor Antagonist

The mechanism of action of NMDA receptor antagonism in PLP is not clear. Memantine has shown some benefits in some case studies but controlled trials have shown mixed results [ 63 , 64 ]. A review concluded that memantine may be useful soon after amputation rather than for use in chronic neuropathic pain conditions [ 65 ].

3.1.8. Other Medications

The beta blocker propranolol and the calcium channel blocker nifedipine have been used for the treatment of PLP [ 60 ]. However, their effectiveness is unclear and further studies are needed. Flupirtine, an NMDA antagonist and potassium channel agonist, has been reported to be effective when used together with opioids in cancer-related neuropathic pain but needs further studies for other etiologies [ 66 ].

3.2. Nonpharmacological Treatment

3.2.1. transcutaneous electrical nerve stimulation (tens).

Transcutaneous electrical nerve stimulation has been found to be helpful in PLP [ 40 ]. Historically, there have been multiple studies showing the effectiveness of TENS of the contralateral limb versus ipsilateral to decrease PLP [ 67 ]. Though there is no strong evidence, low-frequency and high-intensity TENS is thought to be more effective than other doses [ 68 ]. TENS devices are portable, are easy to use, and have few side effects or contraindications.

3.2.2. Mirror Therapy

Mirror therapy was first reported by Ramachandran and Rogers-Ramachandran in 1996 and is suggested to help PLP by resolving the visual-proprioceptive dissociation in the brain [ 69 , 70 ]. The patient watches the reflection of their intact limb moving in a mirror placed parasagittally between their arms or legs while simultaneously moving the phantom hand or foot in a manner similar to what they are observing so that the virtual limb replaces the phantom limb. Simian studies have shown the existence of mirror neurons in the brain which fire both at times when an animal performs an action or observes an action [ 71 ]. Similar homologous neurons have also been discovered in humans [ 72 ]. The presence of mirror neurons in the brain is also supported by the phenomenon of tactile sensation in the phantom limb elicited by touching the virtual image of the limb in the mirror [ 73 ]. When a person with an intact limb observes a person with amputation, he can only “empathize about the amputation” rather than “feel it himself” because of the null input to the mirror neurons from his intact limb. However, a person with an amputation does not receive such null input as the limb is amputated and this results in the activation of mirror neurons which create a perception of tactile sensation. Consequently, since the activation of these mirror neurons modulates somatosensory inputs, their activation may block protopathic pain perception in the phantom limb [ 72 , 73 ]. A randomized controlled trial of mirror therapy in patients with lower leg amputation has shown significant benefit of PLP versus the control group [ 74 ]. Another controlled trial, however, reported that the mirror condition only elicited a significantly greater number of phantom limb movements than the control condition but did not attenuate phantom limb pain and sensations any more than the control condition [ 75 ].

3.2.3. Biofeedback, Integrative, and Behavioral Methods

Although there are earlier reports suggesting temperature biofeedback to be helpful for burning sensation of PLP, there is no specific evidence to match specific types of PLP with specific biofeedback techniques [ 76 ]. There is also a case report of visual feedback helpful in reduction of phantom pain [ 74 ]. Guided imagery, relaxation techniques, and hypnosis have been employed in the treatment of different neuropathic pains and may also be useful for PLP [ 28 , 77 , 78 ]. There are case reports of the beneficial effect of acupuncture for PLP [ 79 , 80 ]. The effectiveness of cognitive behavioral therapy in neuropathic pain syndromes has been reported in a number of case studies [ 81 , 82 ].

3.2.4. Surgical Intervention

Surgical interventions are usually employed when other treatment methods have failed. A case report relates the effectiveness of lesioning the dorsal root entry zone (DREZ) on upper limb phantom pain resulting from brachial plexus avulsions [ 83 ]. Another case report showed that, for selected patients, who have not obtained adequate relief with medical management, spinal cord stimulation was found to be effective [ 84 ]. Case reports of improvement of PLP with deep brain stimulation of the periventricular gray matter and thalamic nuclei have been published [ 85 ]. Motor cortex stimulation was also found to be helpful in a case of PLP [ 86 ].

3.2.5. Electroconvulsive Therapy

A case report of positive outcome has been published even though the mechanism and role of ECT relative to PLP is not well understood [ 87 ].

4. Conclusion

PLP is a relatively common and disabling entity. We have learned much about the pathophysiology and management of PLP since it was first described about five centuries ago. However, there is still no one unifying theory relative to the mechanism of PLP. Specific mechanism-based treatments are still evolving, and most treatments are based on recommendations for neuropathic pain. The evolution of the mechanistic hypothesis from body schema and neuropathic theories to the recently proposed role of mirror neurons in the mechanism of pain have added to our understanding of PLP. Further research is needed to elucidate the relationship between the different proposed mechanisms underlying PLP. A synthesized hypothesis explaining the phenomenon of PLP is necessary in the future for the evolution of more specific mechanism-based treatment recommendations.