EDITORIAL
Virtual reality therapies for phantom limb pain Report on a symposium at the 8th Congress of the European Federation of IASP Chapters (EFIC) in Florence, Italy, on 9–12 October 2013. Accepted for publication 22 May 2014 doi:10.1002/ejp.559
1. Background There is a sizable and rapidly growing population of individuals with limb loss worldwide. An estimated 30 million people in Africa, Asia and Latin America alone require prostheses, orthotics and related services (WHO, 2011). Within the United States, nearly 2 million people are currently living with amputation, and an additional 185,000 people will undergo limb amputation this year (Ziegler-Graham et al., 2008). Amputation may bring a variety of unintended side effects, including painful sensation related to a limb that is no longer there, which is known as phantom limb pain (PLP). Approximately 51% of upper extremity patients experience PLP (Kooijman et al., 2000). Additionally, 76% of upper extremity amputees experience phantom sensations and 49% experience residual limb pain (RLP) or painful sensation in the remaining limb (Kooijman et al., 2000). Between 70% and 80% of patients with lower extremity amputations report either PLP, phantom sensations or RLP, all of which can last indefinitely (Sherman et al., 1984). There are a few prominent theories for PLP, including cortical reorganization (specifically, neuroplasticity in the primary somatosensory cortex); a mismatch between motor commands and expected, but ‘missing’ visual and proprioceptive inputs; preamputation pain; and proprioceptive memory (Katz and Melzack, 1990; Flor et al., 1995; Ramachandran and Hirstein, 1998; Anderson-Barnes et al., 2009). PLP is difficult to treat and multiple drug trials have failed to show efficacy (Ehde et al., 2000). One promising treatment is mirror therapy, which uses the reflection of an intact limb moving in a mirror to create the illusion of the amputated limb being restored (Ramachandran, 1994). This therapy was reported to reduce PLP in a small case series, in which four of five (80%) patients were able to relieve involuntary painful ‘clenching spasms’ in the phantom hand (Ramachandran and Rogers-Ramachandran, 1996). The use of mirror therapy to relieve PLP was © 2014 European Pain Federation - EFIC®
supported through a randomized clinical study by Tsao and colleagues, where it was compared with shammirror and mental visualization therapies (Chan et al., 2007). The key principle of mirror therapy modulating the pain response was shown to be visual feedback – neither the covered mirror nor mental visualization of movements reduced PLP. This principle has been extended to the treatment of PLP in bilateral lower extremity amputees where observation of another person’s legs and feet moving can effectively relieve pain (Tsao and colleagues, unpublished data). Several efforts are now underway to explore treatment of PLP using visual feedback within a virtual setting. Herein, we describe the use of several such platforms, which were discussed at the 8th Congress of the European Federation of IASP Chapters (Florence, Italy, 9–12 October 2013). The initial results from studies conducted using these platforms illustrates the potential to employ visual feedback within a virtual environment for the effective alleviation of PLP due to amputation.
2. Presentations Dr. Mercier and her team developed a method to assess phantom limb motor control and demonstrated a decreased movement speed of the phantom hand in amputees with PLP as compared with amputees who were pain-free (Gagné et al., 2009). Moreover, the amount of electromyographic (EMG) activity recorded in residual limb muscles during phantom movements was positively correlated with the intensity of PLP. This relationship between the perceived ability to move the phantom limb and the severity of pain supports the idea of using ‘motor training’ of the phantom limb together with virtual feedback in order to make phantom movements easier and to alleviate pain. Therefore, Dr. Mercier’s team assessed the effect of a virtual reality (VR) platform. Virtual images of the missing limb moving were obtained by filming the intact limb performing different actions, digitally inverting these videos and Eur J Pain 18 (2014) 897–899
897
Editorial
projecting them on a mirror placed above the position of the phantom limb. After training two times per week for 8 weeks, five of eight patients (63%) reported pain reduction greater than 30% (Mercier and Sirigu, 2009). Differences in outcomes appeared to be related to the susceptibility to the virtual feedback, but studies with larger sample numbers are still needed in order to determine which patients are most likely to benefit from virtual feedback therapy. Dr. Pettifer and his team developed an immersive VR environment in which motions of an amputee’s intact limb are tracked in the real world and transposed onto a computer-generated representation of the patient’s phantom limb in the virtual environment. In order to encourage agency, or the patient’s ability to not only perceive the limb as his or her own but also to control its movement, the patient plays a simple game that involves batting away a ball fired towards him or her from a random direction. In a small-scale trial, five participants with persistent PLP (despite multiple treatment modalities) used the system on a weekly basis; four (80%) reported tangible reduction in pain; two (40%) found they gained some control over their phantom limb’s position, being able to manoeuvre it into a more comfortable state; and one (25%) found that he was even able to exercise some control over the residual limb, which had previously been paralysed for over 12 years. Dr. Cole and his team developed a novel variation on the mirror box, in which motion data are captured directly from a patient’s residual limb (rather than using the opposite remaining limb) and then transformed into goal-directed, virtual action enacted by an avatar in a VR environment (Cole et al., 2009). As the residual limb is moved forward, so too does the VR anatomically intact arm or leg; if the subject stops, then so too does the avatar, to encourage agency. In a preliminary sample of 14 subjects (7 with arm and 7 with leg amputations), 10 (71%) felt the virtual limb to be moved by them as their own and felt sensations of movement within their returned limb. They also reported reductions in their PLP greater than expected from distraction alone. Unsuccessful trials were seen in subjects with paralysis of the phantom and in those with intermittent shooting pain, which was seen in leg amputees. Dr. Tsao, Ms. Perry and their team studied a VR platform where participants with upper-extremity amputations both passively followed and actively drove an avatar limb using surface EMG signals derived from their residual limbs. This platform, entitled the virtual integrated environment (VIE), was developed by the Johns Hopkins University Applied 898 Eur J Pain 18 (2014) 897–899
Physics Laboratory (Laurel, MD, USA) (Alphonso et al., 2012). Using the VIE, the subjects were able to train and complete a full range of virtual arm motions over the course of twenty 30-min sessions. Initial results from six subjects suggest that the VIE alleviates PLP in the majority (83%). Furthermore, the VIE may serve as a unique screening and training device for rehabilitation using an advanced myoelectric prosthetic, the modular prosthetic limb (MPL), as it allows for the assessment of the user’s ability to create discernible and repeatable muscle-to-motion patterns with his or her residual limb (Burck et al., 2009).
3. Discussion Together, we debated the impact of phantom limb qualities, such as range of motion or telescoping (the sensation of the gradual shortening of the limb), on a person’s ability to experience pain relief in response to operating or following the motions of a virtual limb. Several patients with telescoped and immobilized phantom limbs, when treated with mirror therapy, reported a gradual lengthening of their phantom limbs back to the original dimensions and a restoration of full range of motion. Interestingly, these patients lost the full range of motion after the cessation of mirror therapy sessions, while maintaining PLP relief (Tsao and colleagues, unpublished data). Additionally, we discussed the impact of a person’s perceived agency over the virtual limb on his or her subsequent PLP relief, with preliminary data supporting a positive correlation between agency and PLP relief. Patients may need to see their virtually realized limb and to perceive their own sensation from and movement of it for analgesia. Furthermore, it is necessary to both elucidate the timeline of PLP relief and to explore the quality of nonpainful phantom limb sensations throughout VR therapy. Future studies should explore subjective and quantitative reports of these and other qualities, such as whether the limb needs to closely approximate a human limb or should appear cartoon-like to avoid the so-called ‘uncanny valley’ effect whereby flaws in a ‘photorealistic’ rendering of a familiar subject such as the human body can evoke a sense of unease or revulsion in the viewer (Poliakoff et al., 2013). Driven by the popularity of computer games, robust low-cost VR equipment such as the Oculus Rift head-mounted display (Irvine, CA, USA) and the Microsoft Kinect body-tracker (Redmond, WA, USA) are now readily available, making the construction of prototype systems that could be deployed in clinics and patient’s homes feasible; however, the interplay between the quality of rendering, the tasks to be performed and the effect on pain are not yet well understood.
4. Conclusion Collectively, our research represents a variety of techniques utilizing visual feedback, and virtually © 2014 European Pain Federation - EFIC®
Editorial
induced agency, for the treatment of PLP across a diverse rehabilitation population worldwide. The substantial clinical and neuro-rehabilitation implications of these treatments may also be transferrable to other patient populations, such as those with chronic pain and motor deficits, including complex regional pain syndrome, spinal cord injury and brachial plexus avulsion.
Disclaimer The opinions or assertions contained herein are the private views of the authors and are not to be construed as official or as reflecting the views of the Department of the Navy or the Department of Defense of the United States of America. Briana N. Perry1, Catherine Mercier2, Steve R. Pettifer3, Jonathan Cole4, Jack W. Tsao1,5 1 Department of Physical Medicine and Rehabilitation, Walter Reed National Military Medical Center, Bethesda, USA 2 Department of Rehabilitation, University Laval, Quebec, Canada 3 School of Computer Science, University of Manchester, UK 4 Clinical Neurophysiology, Poole Hospital, Poole, UK 5 Departments of Neurology and Physical Medicine and Rehabilitation, Uniformed Services University of the Health Sciences, Bethesda, USA Correspondence Jack W. Tsao E-mail: [email protected] Conflicts of interest None declared.
J.W. (2012). Use of a virtual integrated environment in prosthetic limb development and phantom limb pain. Stud Health Technol Inform 181, 305–309. Anderson-Barnes, V.C., McAuliffe, C., Swanberg, K.M., Tsao, J.W. (2009). Phantom limb pain – a phenomenon of proprioceptive memory? Med Hypotheses 73, 555–558. Burck, J., Zeher, M.J., Armiger, R., Beaty, J.D. (2009). Developing the world’s most advanced prosthetic arm using model-based design. The MathWorks News, Notes. Chan, B.L., Witt, R., Charrow, A.P., Magee, A., Howard, R., Pasquina, P.F., Heilman, K.M., Tsao, J.W. (2007). Mirror therapy for phantom limb pain. N Engl J Med 357, 2206–2207. Cole, J., Crowle, S., Austwick, G., Henderson-Slater, D. (2009). Exploratory findings in virtual induced agency for phantom limb pain. Disabil Rehabil 31, 846–854. Ehde, D.M., Czerniecki, J.M., Smith, D.G., Campbell, K.M., Edwards, W.T., Jensen, M.P., Robinson, L.R. (2000). Chronic phantom sensations, phantom pain, residual limb pain, and other regional pain after lower limb amputation. Arch Phys Med Rehabil 81, 1039–1044. Flor, H., Elbert, T., Knecht, S., Wienbruch, C., Pantev, C., Birbaumer, N. (1995). Phantom-limb pain as a perceptual correlate of cortical reorganization following arm amputation. Nature 375, 482–484. Gagné, M., Reilly, K.T., Hétu, S., Mercier, C. (2009). Motor control over the phantom limb in above-elbow amputees and its relationship with phantom limb pain. Neuroscience 162, 78–86. Katz, J., Melzack, J. (1990). Pain ‘memories’ in phantom-limbs. Pain 43, 319–336. Kooijman, C.M., Dijkstra, P.U., Geertzen, J.H.B., Elzinga, A., van der Schans, C.P. (2000). Phantom pain and phantom sensations in upper limb amputees: An epidemiological study. Pain 87, 33–41. Mercier, C., Sirigu, S. (2009). Training with virtual visual feedback to alleviate phantom limb pain. Neurorehabil Neural Repair 23, 587–594. Poliakoff, E., Beach, N., Best, R., Howard, T.L.J., Gowen, E. (2013). Can looking at a hand make your skin crawl? Peering into the uncanny valley for hands. Perception 42, 998–1000. Ramachandran, V.S. (1994). Phantom limbs, neglect syndromes, repressed memories, and Freudian psychology. Int Rev Neurobiol 37, 291–333. Ramachandran, V.S., Hirstein, W. (1998). The perception of phantom limbs. The D. O. Hebb lecture. Brain 121, 1603–1630. Ramachandran, V.S., Rogers-Ramachandran, D. (1996). Synaesthesia in phantom limbs induced with mirrors. Proc Biol Sci 263, 377–386. Sherman, R.A., Sherman, C.J., Parker, L. (1984). Chronic phantom and stump pain among American veterans: Results of a survey. Pain 18, 83–95. Ziegler-Graham, K., MacKenzie, E.J., Ephraim, P.L., Travison, T.G., Brookmeyer, R. (2008). Estimating the prevalence of limb loss in the United States: 2005 to 2050. Arch Phys Med Rehabil 89, 422–429.
Web references References Alphonso, A.L., Monson, B.T., Zeher, M.J., Armiger, R.S., Weeks, S.R., Burck, J.M., Moran, C., Davoodie, R., Loeb, G., Pasquina, P.F., Tsao,
© 2014 European Pain Federation - EFIC®
UN World Health Organization (WHO). (2011). World Report on Disability: Chapter 4: Rehabilitation. WHO/NMH/VIP/11.01. Retrieved from: http://www.who.int/disabilities/world_report/2011/chapter4.pdf (accessed 25 April 2014).
Eur J Pain 18 (2014) 897–899
899
Virtual reality therapies for phantom limb pain Report on a symposium at the 8th Congress of the European Federation of IASP Chapters (EFIC) in Florence, Italy, on 9–12 October 2013. Accepted for publication 22 May 2014 doi:10.1002/ejp.559
1. Background There is a sizable and rapidly growing population of individuals with limb loss worldwide. An estimated 30 million people in Africa, Asia and Latin America alone require prostheses, orthotics and related services (WHO, 2011). Within the United States, nearly 2 million people are currently living with amputation, and an additional 185,000 people will undergo limb amputation this year (Ziegler-Graham et al., 2008). Amputation may bring a variety of unintended side effects, including painful sensation related to a limb that is no longer there, which is known as phantom limb pain (PLP). Approximately 51% of upper extremity patients experience PLP (Kooijman et al., 2000). Additionally, 76% of upper extremity amputees experience phantom sensations and 49% experience residual limb pain (RLP) or painful sensation in the remaining limb (Kooijman et al., 2000). Between 70% and 80% of patients with lower extremity amputations report either PLP, phantom sensations or RLP, all of which can last indefinitely (Sherman et al., 1984). There are a few prominent theories for PLP, including cortical reorganization (specifically, neuroplasticity in the primary somatosensory cortex); a mismatch between motor commands and expected, but ‘missing’ visual and proprioceptive inputs; preamputation pain; and proprioceptive memory (Katz and Melzack, 1990; Flor et al., 1995; Ramachandran and Hirstein, 1998; Anderson-Barnes et al., 2009). PLP is difficult to treat and multiple drug trials have failed to show efficacy (Ehde et al., 2000). One promising treatment is mirror therapy, which uses the reflection of an intact limb moving in a mirror to create the illusion of the amputated limb being restored (Ramachandran, 1994). This therapy was reported to reduce PLP in a small case series, in which four of five (80%) patients were able to relieve involuntary painful ‘clenching spasms’ in the phantom hand (Ramachandran and Rogers-Ramachandran, 1996). The use of mirror therapy to relieve PLP was © 2014 European Pain Federation - EFIC®
supported through a randomized clinical study by Tsao and colleagues, where it was compared with shammirror and mental visualization therapies (Chan et al., 2007). The key principle of mirror therapy modulating the pain response was shown to be visual feedback – neither the covered mirror nor mental visualization of movements reduced PLP. This principle has been extended to the treatment of PLP in bilateral lower extremity amputees where observation of another person’s legs and feet moving can effectively relieve pain (Tsao and colleagues, unpublished data). Several efforts are now underway to explore treatment of PLP using visual feedback within a virtual setting. Herein, we describe the use of several such platforms, which were discussed at the 8th Congress of the European Federation of IASP Chapters (Florence, Italy, 9–12 October 2013). The initial results from studies conducted using these platforms illustrates the potential to employ visual feedback within a virtual environment for the effective alleviation of PLP due to amputation.
2. Presentations Dr. Mercier and her team developed a method to assess phantom limb motor control and demonstrated a decreased movement speed of the phantom hand in amputees with PLP as compared with amputees who were pain-free (Gagné et al., 2009). Moreover, the amount of electromyographic (EMG) activity recorded in residual limb muscles during phantom movements was positively correlated with the intensity of PLP. This relationship between the perceived ability to move the phantom limb and the severity of pain supports the idea of using ‘motor training’ of the phantom limb together with virtual feedback in order to make phantom movements easier and to alleviate pain. Therefore, Dr. Mercier’s team assessed the effect of a virtual reality (VR) platform. Virtual images of the missing limb moving were obtained by filming the intact limb performing different actions, digitally inverting these videos and Eur J Pain 18 (2014) 897–899
897
Editorial
projecting them on a mirror placed above the position of the phantom limb. After training two times per week for 8 weeks, five of eight patients (63%) reported pain reduction greater than 30% (Mercier and Sirigu, 2009). Differences in outcomes appeared to be related to the susceptibility to the virtual feedback, but studies with larger sample numbers are still needed in order to determine which patients are most likely to benefit from virtual feedback therapy. Dr. Pettifer and his team developed an immersive VR environment in which motions of an amputee’s intact limb are tracked in the real world and transposed onto a computer-generated representation of the patient’s phantom limb in the virtual environment. In order to encourage agency, or the patient’s ability to not only perceive the limb as his or her own but also to control its movement, the patient plays a simple game that involves batting away a ball fired towards him or her from a random direction. In a small-scale trial, five participants with persistent PLP (despite multiple treatment modalities) used the system on a weekly basis; four (80%) reported tangible reduction in pain; two (40%) found they gained some control over their phantom limb’s position, being able to manoeuvre it into a more comfortable state; and one (25%) found that he was even able to exercise some control over the residual limb, which had previously been paralysed for over 12 years. Dr. Cole and his team developed a novel variation on the mirror box, in which motion data are captured directly from a patient’s residual limb (rather than using the opposite remaining limb) and then transformed into goal-directed, virtual action enacted by an avatar in a VR environment (Cole et al., 2009). As the residual limb is moved forward, so too does the VR anatomically intact arm or leg; if the subject stops, then so too does the avatar, to encourage agency. In a preliminary sample of 14 subjects (7 with arm and 7 with leg amputations), 10 (71%) felt the virtual limb to be moved by them as their own and felt sensations of movement within their returned limb. They also reported reductions in their PLP greater than expected from distraction alone. Unsuccessful trials were seen in subjects with paralysis of the phantom and in those with intermittent shooting pain, which was seen in leg amputees. Dr. Tsao, Ms. Perry and their team studied a VR platform where participants with upper-extremity amputations both passively followed and actively drove an avatar limb using surface EMG signals derived from their residual limbs. This platform, entitled the virtual integrated environment (VIE), was developed by the Johns Hopkins University Applied 898 Eur J Pain 18 (2014) 897–899
Physics Laboratory (Laurel, MD, USA) (Alphonso et al., 2012). Using the VIE, the subjects were able to train and complete a full range of virtual arm motions over the course of twenty 30-min sessions. Initial results from six subjects suggest that the VIE alleviates PLP in the majority (83%). Furthermore, the VIE may serve as a unique screening and training device for rehabilitation using an advanced myoelectric prosthetic, the modular prosthetic limb (MPL), as it allows for the assessment of the user’s ability to create discernible and repeatable muscle-to-motion patterns with his or her residual limb (Burck et al., 2009).
3. Discussion Together, we debated the impact of phantom limb qualities, such as range of motion or telescoping (the sensation of the gradual shortening of the limb), on a person’s ability to experience pain relief in response to operating or following the motions of a virtual limb. Several patients with telescoped and immobilized phantom limbs, when treated with mirror therapy, reported a gradual lengthening of their phantom limbs back to the original dimensions and a restoration of full range of motion. Interestingly, these patients lost the full range of motion after the cessation of mirror therapy sessions, while maintaining PLP relief (Tsao and colleagues, unpublished data). Additionally, we discussed the impact of a person’s perceived agency over the virtual limb on his or her subsequent PLP relief, with preliminary data supporting a positive correlation between agency and PLP relief. Patients may need to see their virtually realized limb and to perceive their own sensation from and movement of it for analgesia. Furthermore, it is necessary to both elucidate the timeline of PLP relief and to explore the quality of nonpainful phantom limb sensations throughout VR therapy. Future studies should explore subjective and quantitative reports of these and other qualities, such as whether the limb needs to closely approximate a human limb or should appear cartoon-like to avoid the so-called ‘uncanny valley’ effect whereby flaws in a ‘photorealistic’ rendering of a familiar subject such as the human body can evoke a sense of unease or revulsion in the viewer (Poliakoff et al., 2013). Driven by the popularity of computer games, robust low-cost VR equipment such as the Oculus Rift head-mounted display (Irvine, CA, USA) and the Microsoft Kinect body-tracker (Redmond, WA, USA) are now readily available, making the construction of prototype systems that could be deployed in clinics and patient’s homes feasible; however, the interplay between the quality of rendering, the tasks to be performed and the effect on pain are not yet well understood.
4. Conclusion Collectively, our research represents a variety of techniques utilizing visual feedback, and virtually © 2014 European Pain Federation - EFIC®
Editorial
induced agency, for the treatment of PLP across a diverse rehabilitation population worldwide. The substantial clinical and neuro-rehabilitation implications of these treatments may also be transferrable to other patient populations, such as those with chronic pain and motor deficits, including complex regional pain syndrome, spinal cord injury and brachial plexus avulsion.
Disclaimer The opinions or assertions contained herein are the private views of the authors and are not to be construed as official or as reflecting the views of the Department of the Navy or the Department of Defense of the United States of America. Briana N. Perry1, Catherine Mercier2, Steve R. Pettifer3, Jonathan Cole4, Jack W. Tsao1,5 1 Department of Physical Medicine and Rehabilitation, Walter Reed National Military Medical Center, Bethesda, USA 2 Department of Rehabilitation, University Laval, Quebec, Canada 3 School of Computer Science, University of Manchester, UK 4 Clinical Neurophysiology, Poole Hospital, Poole, UK 5 Departments of Neurology and Physical Medicine and Rehabilitation, Uniformed Services University of the Health Sciences, Bethesda, USA Correspondence Jack W. Tsao E-mail: [email protected] Conflicts of interest None declared.
J.W. (2012). Use of a virtual integrated environment in prosthetic limb development and phantom limb pain. Stud Health Technol Inform 181, 305–309. Anderson-Barnes, V.C., McAuliffe, C., Swanberg, K.M., Tsao, J.W. (2009). Phantom limb pain – a phenomenon of proprioceptive memory? Med Hypotheses 73, 555–558. Burck, J., Zeher, M.J., Armiger, R., Beaty, J.D. (2009). Developing the world’s most advanced prosthetic arm using model-based design. The MathWorks News, Notes. Chan, B.L., Witt, R., Charrow, A.P., Magee, A., Howard, R., Pasquina, P.F., Heilman, K.M., Tsao, J.W. (2007). Mirror therapy for phantom limb pain. N Engl J Med 357, 2206–2207. Cole, J., Crowle, S., Austwick, G., Henderson-Slater, D. (2009). Exploratory findings in virtual induced agency for phantom limb pain. Disabil Rehabil 31, 846–854. Ehde, D.M., Czerniecki, J.M., Smith, D.G., Campbell, K.M., Edwards, W.T., Jensen, M.P., Robinson, L.R. (2000). Chronic phantom sensations, phantom pain, residual limb pain, and other regional pain after lower limb amputation. Arch Phys Med Rehabil 81, 1039–1044. Flor, H., Elbert, T., Knecht, S., Wienbruch, C., Pantev, C., Birbaumer, N. (1995). Phantom-limb pain as a perceptual correlate of cortical reorganization following arm amputation. Nature 375, 482–484. Gagné, M., Reilly, K.T., Hétu, S., Mercier, C. (2009). Motor control over the phantom limb in above-elbow amputees and its relationship with phantom limb pain. Neuroscience 162, 78–86. Katz, J., Melzack, J. (1990). Pain ‘memories’ in phantom-limbs. Pain 43, 319–336. Kooijman, C.M., Dijkstra, P.U., Geertzen, J.H.B., Elzinga, A., van der Schans, C.P. (2000). Phantom pain and phantom sensations in upper limb amputees: An epidemiological study. Pain 87, 33–41. Mercier, C., Sirigu, S. (2009). Training with virtual visual feedback to alleviate phantom limb pain. Neurorehabil Neural Repair 23, 587–594. Poliakoff, E., Beach, N., Best, R., Howard, T.L.J., Gowen, E. (2013). Can looking at a hand make your skin crawl? Peering into the uncanny valley for hands. Perception 42, 998–1000. Ramachandran, V.S. (1994). Phantom limbs, neglect syndromes, repressed memories, and Freudian psychology. Int Rev Neurobiol 37, 291–333. Ramachandran, V.S., Hirstein, W. (1998). The perception of phantom limbs. The D. O. Hebb lecture. Brain 121, 1603–1630. Ramachandran, V.S., Rogers-Ramachandran, D. (1996). Synaesthesia in phantom limbs induced with mirrors. Proc Biol Sci 263, 377–386. Sherman, R.A., Sherman, C.J., Parker, L. (1984). Chronic phantom and stump pain among American veterans: Results of a survey. Pain 18, 83–95. Ziegler-Graham, K., MacKenzie, E.J., Ephraim, P.L., Travison, T.G., Brookmeyer, R. (2008). Estimating the prevalence of limb loss in the United States: 2005 to 2050. Arch Phys Med Rehabil 89, 422–429.
Web references References Alphonso, A.L., Monson, B.T., Zeher, M.J., Armiger, R.S., Weeks, S.R., Burck, J.M., Moran, C., Davoodie, R., Loeb, G., Pasquina, P.F., Tsao,
© 2014 European Pain Federation - EFIC®
UN World Health Organization (WHO). (2011). World Report on Disability: Chapter 4: Rehabilitation. WHO/NMH/VIP/11.01. Retrieved from: http://www.who.int/disabilities/world_report/2011/chapter4.pdf (accessed 25 April 2014).
Eur J Pain 18 (2014) 897–899
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