Phantom pain
Encyclopedia
Phantom pain sensations are described as perceptions that an individual experiences relating to a limb or an organ that is not physically part of the body. Limb loss is a result of either removal by amputation
or congenital limb deficiency (Giummarra et al., 2007). However, phantom limb sensations can also occur following nerve avulsion or spinal cord
injury. Sensations are recorded most frequently following the amputation of an arm or a leg, but may also occur following the removal of a breast or an internal organ.
Phantom limb pain is the feeling of pain
in an absent limb or a portion of a limb.
The pain sensation varies from individual to individual.
Phantom limb
sensation is the term given to any sensory phenomenon (except pain) which is felt at an absent limb or a portion of the limb. It has been known that at least 80% of amputees experience phantom sensations at some time of their lives. Some experience some level of this phantom pain and feeling in the missing limb for the rest of their lives.
There are various types of sensations that may be felt:
The term “phantom limb” was first coined by American neurologist Silas Weir Mitchell
in 1871 (Halligan, 2002). Mitchell described that “thousands of spirit limbs were haunting as many good soldiers, every now and then tormenting them” (Bittar et al., 2005). However, in 1551, French military surgeon Ambroise Paré
recorded the first documentation of phantom limb pain when he reported that, “For the patients, long after the amputation is made, say that they still feel pain in the amputated part” (Bittar et al., 2005).
wears off, and the remaining 25% of patients experience phantoms within a few days or weeks (Ramachandran and Herstein, 1998). Of those experiencing innocuous sensations, a majority of patients also report distinct painful sensations.
The prevalence of phantom limb pain differs based on the location of the amputation. The prevalence of phantom pain in upper limb amputees is nearly 82%, while the prevalence of pain in lower limb amputees is only 54% (Kooijman et al., 2000). Age and gender have not been shown to affect the onset or duration of phantom limb pain. Although it has not been fully explored, one investigation of lower limb amputation observed that as stump length decreased, there was a greater incidence of moderate and severe phantom pain (Bittar et al., 2005).
, involved in the transmission of pain signals, is usually expressed by Aδ and C fibers, but following peripheral nerve damage, substance P is expressed by Aβ fibers (Bittar et al., 2005). This leads to hyperexcitability of the spinal cord, which usually occurs only in the presence of noxious stimuli. Because patients with complete spinal cord injury have experienced phantom pains, there must be an underlying central mechanism responsible for the generation of phantom pains.
remains largely stable throughout life. It was thought, until about 30 years ago, that no new neural circuits could be formed in the adult mammalian brain (Ramachandran and Hirstein, 1998). Recently, functional MRI studies in amputees have shown that almost all patients have experienced motor cortical remapping (Cruz et al., 2003). The majority of motor reorganization has occurred as a downward shift of the hand area of the cortex onto the area of face representation, especially the lips. Sometimes there is a side shift of the hand motor cortex
to the ipsilateral cortex (Cruz et al., 2003). In patients with phantom limb pain, the reorganization was great enough to cause a change in cortical lip representation into the hand areas only during lip movements (Cruz et al., 2003). It has also been found that there is a high correlation between the magnitude of phantom limb pain and the extent to which the shift of the cortical representation of the mouth into the hand area in motor and somatosensory cortical reorganization has occurred (Karl et al., 2001). Additionally, as phantom pains in upper extremity amputees increased, there was a higher degree of medial shift of the facial motor representation (Karl et al., 2001). There are
Multiple theories that try to explain how cortical remapping occurs in amputees, but none have been supported to a great extent.
and the cortex, and the cortex and the limbic system
(Bittar et al., 2005). It is a theory that extends beyond body schema theory and incorporates the conscious awareness of oneself. This theory proposes that conscious awareness and the perception of self are generated in the brain via patterns of input that can be modified by different perceptual inputs (Giummarra et al., 2007). 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 (Bittar et al., 2005). The input systems contributing to the neurosignature are primarily the somatosensory, limbic, and thalamocortical systems. The neuromatrix theory aims to explain how certain activities associated with pain lead to the conscious perception of phantom pain. The persistence of the neurosignature, even after limb amputation, may be the cause of phantom sensations and pain. Phantom pain may arise from abnormal reorganization in the neuromatrix to a pre-existing pain state (Melzack, 1992).
Opposition to the neuromatrix 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 (Bittar et al., 2005). In addition, a major limitation of the neuromatrix theory is that it too broadly accounts for various aspects of phantom limb perception. It is also likely that it is too difficult to be tested empirically, especially when testing painless phantom sensations (Giummarra et al., 2007).
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 ineffective. 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 less than 30% (Bittar et al., 2005). It is important to note that this rate of success does not exceed the placebo
effect. It is also important to note that because the degree of cortical reorganization is proportional to phantom limb pains, any perturbations to the amputated regions may increase pain perception (Bittar et al., 2005).
therapy allows for illusions of movement and touch in a phantom limb by inducing somatosensory and motor pathway coupling between the phantom and real limb (Giummarra et al., 2007). Many patients experience pain as a result of a clenched phantom limb, and because phantom limbs are not under voluntary control, unclenching becomes impossible (Ramachandran and Rogers-Ramachandran, 1996). 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 and Rogers-Ramachandran believed that if the brain received visual feedback that the limb had moved, then the phantom limb would become unparalyzed (Ramachandran and Rogers-Ramachandran, 1996).
Although the use of mirror therapy has been shown to be effective in some cases there is still no widely accepted theory of how it works. In a 2010 study of phantom limb pain, Martin Diers and his colleagues found that "In a randomized controlled trial that used graded motor imagery...and mirror training, patients with complex regional pain syndrome or phantom limb pain showed a decrease in pain as well as an improvement in function post-treatment and at the 6-month follow-up. And it was shown that the order of treatment mattered." This study found that mirrored imagery produced no significant cortical activity in patients with phantom limb pain and concluded that "The optimal method to alter pain and brain representation, and the brain mechanisms underlying the effects [of] mirror training or motor imagery, are still unclear." (Diers et al., 2010)
A number of small scale research studies have shown encouraging results, however there is no current consensus as to the effectiveness of mirror therapy. Recent reviews of the published research literature by Mosely (Moseley et al., 2008) and Ezendam (Ezendam et al., 2009) concluded that much of the evidence supporting mirror therapy is anecdotal or comes from studies that had weak methodological quality. In 2011 a large scale review of the literature on mirror therapy by Rothgangel (Rothgangel et al., 2011) summarized the current research as follows.
"For stroke there is a moderate quality of evidence that MT [Mirror Therapy] as an additional intervention improves recovery of arm function, and a low quality of evidence regarding lower limb function and pain after stroke. The quality of evidence in patients with complex regional pain syndrome and phantom limb pain is also low. Firm conclusions could not be drawn. Little is known about which patients are likely to benefit most from MT, and how MT should preferably be applied. Future studies with clear descriptions of intervention protocols should focus on standardized outcome measures and systematically register adverse effects."(Rothgangel et al., 2011)
, and sodium channel blockers, mainly carbamazepine
, are often used to relieve chronic pain, and recently have been used in an attempt to reduce phantom pains. Pain relief may also be achieved through use of opioids, ketamine
, calcitonin
, and lidocaine
(Bittar et al., 2005).
, 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 (Bittar et al., 2005). It was found that all three patients studied had gained satisfactory pain relief from the deep brain stimulation. Pain had not been completely eliminated, but the intensity had been reduced by over 50% and the burning component had completely vanished (Bittar et al., 2005).
Amputation
Amputation is the removal of a body extremity by trauma, prolonged constriction, or surgery. As a surgical measure, it is used to control pain or a disease process in the affected limb, such as malignancy or gangrene. In some cases, it is carried out on individuals as a preventative surgery for...
or congenital limb deficiency (Giummarra et al., 2007). However, phantom limb sensations can also occur following nerve avulsion or spinal cord
Spinal cord
The spinal cord is a long, thin, tubular bundle of nervous tissue and support cells that extends from the brain . The brain and spinal cord together make up the central nervous system...
injury. Sensations are recorded most frequently following the amputation of an arm or a leg, but may also occur following the removal of a breast or an internal organ.
Phantom limb pain is the feeling of pain
Pain
Pain is an unpleasant sensation often caused by intense or damaging stimuli such as stubbing a toe, burning a finger, putting iodine on a cut, and bumping the "funny bone."...
in an absent limb or a portion of a limb.
The pain sensation varies from individual to individual.
Phantom limb
Phantom limb
A phantom limb is the sensation that an amputated or missing limb is still attached to the body and is moving appropriately with other body parts. 2 out of 3 combat veterans report this feeling. Approximately 60 to 80% of individuals with an amputation experience phantom sensations in their...
sensation is the term given to any sensory phenomenon (except pain) which is felt at an absent limb or a portion of the limb. It has been known that at least 80% of amputees experience phantom sensations at some time of their lives. Some experience some level of this phantom pain and feeling in the missing limb for the rest of their lives.
There are various types of sensations that may be felt:
- Sensations related to the phantom limb's posture, length and volume e.g. feeling that the phantom limb is behaving just like a normal limb like sitting with the knee bent or feeling that the phantom limb is as heavy as the other limb. Sometimes, an amputee will experience a sensation called telescoping. This is the feeling that the phantom limb is gradually shortening over time.
- Sensations of movement (e.g. feeling that the phantom foot is moving).
- Sensations of touch, temperature, pressure and itchiness. Many amputees report of feeling heat, tingling, itchiness, and pain.
The term “phantom limb” was first coined by American neurologist Silas Weir Mitchell
Silas Weir Mitchell
Silas Weir Mitchell was an American physician and writer.He was son of a physician, John Kearsley Mitchell , and was born in Philadelphia, Pennsylvania....
in 1871 (Halligan, 2002). Mitchell described that “thousands of spirit limbs were haunting as many good soldiers, every now and then tormenting them” (Bittar et al., 2005). However, in 1551, French military surgeon Ambroise Paré
Ambroise Paré
Ambroise Paré was a French surgeon. He was the great official royal surgeon for kings Henry II, Francis II, Charles IX and Henry III and is considered as one of the fathers of surgery and modern forensic pathology. He was a leader in surgical techniques and battlefield medicine, especially the...
recorded the first documentation of phantom limb pain when he reported that, “For the patients, long after the amputation is made, say that they still feel pain in the amputated part” (Bittar et al., 2005).
Signs and symptoms
Phantom pain involves the sensation of pain in a part of the body that has been removed.Epidemiology
Phantom limb pain and phantom limb sensations are linked, but must be differentiated from one another. While phantom limb sensations are experienced by those with congenital limb deficiency, spinal cord injury, and amputation, phantom limb pain occurs almost exclusively as a result of amputation (Kooijman et al., 2000). Almost immediately following the amputation of a limb, 90-98% of patients report experiencing a phantom sensation. Nearly 75% of individuals experience the phantom as soon as anesthesiaAnesthesia
Anesthesia, or anaesthesia , traditionally meant the condition of having sensation blocked or temporarily taken away...
wears off, and the remaining 25% of patients experience phantoms within a few days or weeks (Ramachandran and Herstein, 1998). Of those experiencing innocuous sensations, a majority of patients also report distinct painful sensations.
The prevalence of phantom limb pain differs based on the location of the amputation. The prevalence of phantom pain in upper limb amputees is nearly 82%, while the prevalence of pain in lower limb amputees is only 54% (Kooijman et al., 2000). Age and gender have not been shown to affect the onset or duration of phantom limb pain. Although it has not been fully explored, one investigation of lower limb amputation observed that as stump length decreased, there was a greater incidence of moderate and severe phantom pain (Bittar et al., 2005).
Pathophysiology
The neurological basis and mechanisms for phantom limb pain are all derived from experimental theories and observations. Little is known about the true mechanism causing phantom pains, and many theories highly overlap. Historically, phantom pains were thought to originate from neuromas located at the stump tip. Traumatic neuromas, or non-tumor nerve injuries, often arise from surgeries and result from the abnormal growth of injured nerve fibers. Although stump neuromas contribute to phantom pains, they are not the sole cause. This is because patients with congenital limb deficiency can sometimes, although rarely, experience phantom pains. This suggests that there is a central representation of the limb responsible for painful sensations (Ramachandran and Herstein, 1998). Currently, theories are based on altered neurological pathways and cortical reorganization. Although they are highly intertwined, mechanisms are often separated into peripheral, spinal, and central mechanisms.Peripheral mechanisms
Neuromas formed from injured nerve endings at the stump site are able to fire abnormal action potentials, and were historically thought to be the main cause of phantom limb pain. Although neuromas are able to contribute to phantom pain, pain is not completely eliminated when peripheral nerves are treated with conduction blocking agents (Ramachandran and Hirstein, 1998). Physical stimulation of neuromas can increase C fiber activity, thus increasing phantom pain, but pain still persists once the neuromas have ceased firing action potentials. The peripheral nervous system is thought to have at most a modulation effect on phantom limb pain (Bitter et al., 2005)Spinal mechanisms
In addition to peripheral mechanisms, spinal mechanisms are thought to have an influencing role in phantom pains. Peripheral nerve injury can lead to the degeneration of C fibers in the dorsal horn of the spinal cord, and terminating A fibers may subsequently branch into the same lamina (Bittar et al., 2005). If this occurs, A fiber inputs could be reported as noxious stimuli. Substance PSubstance P
In the field of neuroscience, substance P is a neuropeptide: an undecapeptide that functions as a neurotransmitter and as a neuromodulator. It belongs to the tachykinin neuropeptide family. Substance P and its closely related neuropeptide neurokinin A are produced from a polyprotein precursor...
, involved in the transmission of pain signals, is usually expressed by Aδ and C fibers, but following peripheral nerve damage, substance P is expressed by Aβ fibers (Bittar et al., 2005). This leads to hyperexcitability of the spinal cord, which usually occurs only in the presence of noxious stimuli. Because patients with complete spinal cord injury have experienced phantom pains, there must be an underlying central mechanism responsible for the generation of phantom pains.
Central mechanisms and cortical remapping
Under ordinary circumstances, the genetically determined circuitry in the brainBrain
The brain is the center of the nervous system in all vertebrate and most invertebrate animals—only a few primitive invertebrates such as sponges, jellyfish, sea squirts and starfishes do not have one. It is located in the head, usually close to primary sensory apparatus such as vision, hearing,...
remains largely stable throughout life. It was thought, until about 30 years ago, that no new neural circuits could be formed in the adult mammalian brain (Ramachandran and Hirstein, 1998). Recently, functional MRI studies in amputees have shown that almost all patients have experienced motor cortical remapping (Cruz et al., 2003). The majority of motor reorganization has occurred as a downward shift of the hand area of the cortex onto the area of face representation, especially the lips. Sometimes there is a side shift of the hand motor cortex
Motor cortex
Motor cortex is a term that describes regions of the cerebral cortex involved in the planning, control, and execution of voluntary motor functions.-Anatomy of the motor cortex :The motor cortex can be divided into four main parts:...
to the ipsilateral cortex (Cruz et al., 2003). In patients with phantom limb pain, the reorganization was great enough to cause a change in cortical lip representation into the hand areas only during lip movements (Cruz et al., 2003). It has also been found that there is a high correlation between the magnitude of phantom limb pain and the extent to which the shift of the cortical representation of the mouth into the hand area in motor and somatosensory cortical reorganization has occurred (Karl et al., 2001). Additionally, as phantom pains in upper extremity amputees increased, there was a higher degree of medial shift of the facial motor representation (Karl et al., 2001). There are
Multiple theories that try to explain how cortical remapping occurs in amputees, but none have been supported to a great extent.
The neuromatrix
The neuromatrix theory proposes that there is an extensive network connecting the thalamusThalamus
The thalamus is a midline paired symmetrical structure within the brains of vertebrates, including humans. It is situated between the cerebral cortex and midbrain, both in terms of location and neurological connections...
and the cortex, and the cortex and the limbic system
Limbic system
The limbic system is a set of brain structures including the hippocampus, amygdala, anterior thalamic nuclei, septum, limbic cortex and fornix, which seemingly support a variety of functions including emotion, behavior, long term memory, and olfaction. The term "limbic" comes from the Latin...
(Bittar et al., 2005). It is a theory that extends beyond body schema theory and incorporates the conscious awareness of oneself. This theory proposes that conscious awareness and the perception of self are generated in the brain via patterns of input that can be modified by different perceptual inputs (Giummarra et al., 2007). 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 (Bittar et al., 2005). The input systems contributing to the neurosignature are primarily the somatosensory, limbic, and thalamocortical systems. The neuromatrix theory aims to explain how certain activities associated with pain lead to the conscious perception of phantom pain. The persistence of the neurosignature, even after limb amputation, may be the cause of phantom sensations and pain. Phantom pain may arise from abnormal reorganization in the neuromatrix to a pre-existing pain state (Melzack, 1992).
Opposition to the neuromatrix 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 (Bittar et al., 2005). In addition, a major limitation of the neuromatrix theory is that it too broadly accounts for various aspects of phantom limb perception. It is also likely that it is too difficult to be tested empirically, especially when testing painless phantom sensations (Giummarra et al., 2007).
Management
Various methods have been used to treat phantom limb pain. Doctors may prescribe medications to reduce the pain. Some antidepressants or antiepileptics have been shown to have a beneficial effect on reducing phantom limb pain. Often physical methods such as light massage, electrical stimulation, and hot and cold therapy have been used with variable results.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 ineffective. 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 less than 30% (Bittar et al., 2005). It is important to note that this rate of success does not exceed the placebo
Placebo
A placebo is a simulated or otherwise medically ineffectual treatment for a disease or other medical condition intended to deceive the recipient...
effect. It is also important to note that because the degree of cortical reorganization is proportional to phantom limb pains, any perturbations to the amputated regions may increase pain perception (Bittar et al., 2005).
Mirror box therapy
Mirror boxMirror box
A mirror box is a box with two mirrors in the center , invented by Vilayanur S. Ramachandran to help alleviate phantom limb pain, in which patients feel they still have a limb after having it amputated....
therapy allows for illusions of movement and touch in a phantom limb by inducing somatosensory and motor pathway coupling between the phantom and real limb (Giummarra et al., 2007). Many patients experience pain as a result of a clenched phantom limb, and because phantom limbs are not under voluntary control, unclenching becomes impossible (Ramachandran and Rogers-Ramachandran, 1996). 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 and Rogers-Ramachandran believed that if the brain received visual feedback that the limb had moved, then the phantom limb would become unparalyzed (Ramachandran and Rogers-Ramachandran, 1996).
Although the use of mirror therapy has been shown to be effective in some cases there is still no widely accepted theory of how it works. In a 2010 study of phantom limb pain, Martin Diers and his colleagues found that "In a randomized controlled trial that used graded motor imagery...and mirror training, patients with complex regional pain syndrome or phantom limb pain showed a decrease in pain as well as an improvement in function post-treatment and at the 6-month follow-up. And it was shown that the order of treatment mattered." This study found that mirrored imagery produced no significant cortical activity in patients with phantom limb pain and concluded that "The optimal method to alter pain and brain representation, and the brain mechanisms underlying the effects [of] mirror training or motor imagery, are still unclear." (Diers et al., 2010)
A number of small scale research studies have shown encouraging results, however there is no current consensus as to the effectiveness of mirror therapy. Recent reviews of the published research literature by Mosely (Moseley et al., 2008) and Ezendam (Ezendam et al., 2009) concluded that much of the evidence supporting mirror therapy is anecdotal or comes from studies that had weak methodological quality. In 2011 a large scale review of the literature on mirror therapy by Rothgangel (Rothgangel et al., 2011) summarized the current research as follows.
"For stroke there is a moderate quality of evidence that MT [Mirror Therapy] as an additional intervention improves recovery of arm function, and a low quality of evidence regarding lower limb function and pain after stroke. The quality of evidence in patients with complex regional pain syndrome and phantom limb pain is also low. Firm conclusions could not be drawn. Little is known about which patients are likely to benefit most from MT, and how MT should preferably be applied. Future studies with clear descriptions of intervention protocols should focus on standardized outcome measures and systematically register adverse effects."(Rothgangel et al., 2011)
Pharmacological treatment
Pharmacological techniques are often continued in conjunction with other treatment options. Doses or pain medications needed often drop substantially when combined with other techniques, but rarely are discontinued completely. Tricyclic antidepressants, such as amitriptylineAmitriptyline
Amitriptyline is a tricyclic antidepressant . It is the most widely used TCA and has at least equal efficacy against depression as the newer class of SSRIs...
, and sodium channel blockers, mainly carbamazepine
Carbamazepine
Carbamazepine is an anticonvulsant and mood-stabilizing drug used primarily in the treatment of epilepsy and bipolar disorder, as well as trigeminal neuralgia...
, are often used to relieve chronic pain, and recently have been used in an attempt to reduce phantom pains. Pain relief may also be achieved through use of opioids, ketamine
Ketamine
Ketamine is a drug used in human and veterinary medicine. Its hydrochloride salt is sold as Ketanest, Ketaset, and Ketalar. Pharmacologically, ketamine is classified as an NMDA receptor antagonist...
, calcitonin
Calcitonin
Calcitonin is a 32-amino acid linear polypeptide hormone that is producedin humans primarily by the parafollicular cells of the thyroid, and in many other animals in the ultimobranchial body. It acts to reduce blood calcium , opposing the effects of parathyroid hormone . Calcitonin has been found...
, and lidocaine
Lidocaine
Lidocaine , Xylocaine, or lignocaine is a common local anesthetic and antiarrhythmic drug. Lidocaine is used topically to relieve itching, burning and pain from skin inflammations, injected as a dental anesthetic or as a local anesthetic for minor surgery.- History :Lidocaine, the first amino...
(Bittar et al., 2005).
Deep-brain stimulation
Deep brain stimulation is a surgical technique used to alleviate patients from phantom limb pain. 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 anestheticLocal anesthetic
A local anesthetic is a drug that causes reversible local anesthesia, generally for the aim of having local analgesic effect, that is, inducing absence of pain sensation, although other local senses are often affected as well...
, because patient feedback during the operation is needed. In the study conducted by Bittar et al., a radiofrequency electrode
Electrode
An electrode is an electrical conductor used to make contact with a nonmetallic part of a circuit...
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
Clavicle
In human anatomy, the clavicle or collar bone is a long bone of short length that serves as a strut between the scapula and the sternum. It is the only long bone in body that lies horizontally...
to stimulate the electrode (Bittar et al., 2005). It was found that all three patients studied had gained satisfactory pain relief from the deep brain stimulation. Pain had not been completely eliminated, but the intensity had been reduced by over 50% and the burning component had completely vanished (Bittar et al., 2005).
External links
- Information about Phantom Pain from The UMC St Radboud amputee website