Phantom limbs: pain, embodiment, and scientific advances in integrative therapies.

Research over the past two decades has begun to identify some of the key mechanisms underlying phantom limb pain and sensations; however, this continues to be a clinically challenging condition to manage. Treatment of phantom pain, like all chronic pain conditions, demands a holistic approach that takes into consideration peripheral, spinal, and central neuroplastic mechanisms. In this review, we focus on nonpharmacological treatments tailored to reverse the maladaptive neuroplasticity associated with phantom pain. Recent scientific advances emerging from interdisciplinary research between neuroscience, virtual reality, robotics, and prosthetics show the greatest promise for alternative embodiment and maintaining the integrity of the multifaceted representation of the body in the brain. Importantly, these advances have been found to prevent and reduce phantom limb pain. In particular, therapies that involve sensory and/or motor retraining, most naturally through the use of integrative prosthetic devices, as well as peripheral (e.g., transcutaneous electrical nerve stimulation) or central (e.g., transcranial magnetic stimulation or deep brain stimulation) stimulation techniques, have been found to both restore the neural representation of the missing limb and to reduce the intensity of phantom pain. While the evidence for the efficacy of these therapies is mounting, but well-controlled and large-scale studies are still needed. WIREs Cogn Sci 2014, 5:221-231. doi: 10.1002/wcs.1277 CONFLICT OF INTEREST: The authors have no financial or other relationship that might lead to a conflict of interest. For further resources related to this article, please visit the WIREs website.

[1]  Luke A. Henderson,et al.  Functional Reorganization of the Brain in Humans Following Spinal Cord Injury: Evidence for Underlying Changes in Cortical Anatomy , 2011, The Journal of Neuroscience.

[2]  J. Bradshaw,et al.  Mechanisms underlying embodiment, disembodiment and loss of embodiment , 2008, Neuroscience & Biobehavioral Reviews.

[3]  Kerstin Hagberg,et al.  Osseoperception and Osseointegrated Prosthetic Limbs , 2008 .

[4]  Wolfgang Rosenstiel,et al.  A brain-computer interface for chronic pain patients using epidural ECoG and visual feedback , 2012, 2012 IEEE 12th International Conference on Bioinformatics & Bioengineering (BIBE).

[5]  Francine Malouin,et al.  Decreasing phantom limb pain through observation of action and imagery: a case series. , 2011, Pain medicine.

[6]  O Blanke,et al.  Functional and Neural Mechanisms of Embodiment: Importance of the Vestibular System and the Temporal Parietal Junction , 2006, Reviews in the neurosciences.

[7]  Scott H. Frey,et al.  Former Hand Territory Activity Increases After Amputation During Intact Hand Movements, but Is Unaffected by Illusory Visual Feedback , 2012, Neurorehabilitation and neural repair.

[8]  W. Penfield,et al.  The Cerebral Cortex of Man: A Clinical Study of Localization of Function , 1968 .

[9]  Keehoon Kim,et al.  Robotic touch shifts perception of embodiment to a prosthesis in targeted reinnervation amputees. , 2011, Brain : a journal of neurology.

[10]  G. Moseley,et al.  Phantom limb pain and bodily awareness: current concepts and future directions , 2011, Current opinion in anaesthesiology.

[11]  Joel Katz,et al.  Psychophysiological Contributions to Phantom Limbs * , 1992, Canadian journal of psychiatry. Revue canadienne de psychiatrie.

[12]  W. Miltner,et al.  Plasticity in the Visual System is Associated with Prosthesis Use in Phantom Limb Pain , 2013, Front. Hum. Neurosci..

[13]  Ivanei E. Bramati,et al.  Functional Expansion of Sensorimotor Representation and Structural Reorganization of Callosal Connections in Lower Limb Amputees , 2012, The Journal of Neuroscience.

[14]  J. Tastevin,et al.  En partant de l'expérience d'Aristote les déplacements artificiels des parties du corps ne sont pas suivis par le sentiment de ces parties ni par les sensations qu'on peut y produire. , 1937 .

[15]  N. Bolognini,et al.  Motor and parietal cortex stimulation for phantom limb pain and sensations , 2013, PAIN®.

[16]  Nicholas P. Holmes,et al.  Visual bias of unseen hand position with a mirror: spatial and temporal factors , 2005, Experimental Brain Research.

[17]  Martin Lotze,et al.  Role of distorted body image in pain , 2007, Current rheumatology reports.

[18]  J. Paysant,et al.  Temporary phantom limbs evoked by vestibular caloric stimulation in amputees. , 2001, Neuropsychiatry, neuropsychology, and behavioral neurology.

[19]  H. Flor,et al.  Phantom limb pain: a case of maladaptive CNS plasticity? , 2006, Nature Reviews Neuroscience.

[20]  G. Stratton,et al.  IV.—THE SPATIAL HARMONY OF TOUCH AND SIGHT. , 1899 .

[21]  E J MacKenzie,et al.  Rehabilitation and the long-term outcomes of persons with trauma-related amputations. , 2000, Archives of physical medicine and rehabilitation.

[22]  Heidi Johansen-Berg,et al.  Phantom pain is associated with preserved structure and function in the former hand area , 2013, Nature Communications.

[23]  Ellen Leibenluft,et al.  A Developmental Examination of Amygdala Response to Facial Expressions , 2008, Journal of Cognitive Neuroscience.

[24]  K. D. Davis,et al.  Stability of phantom limb phenomena after upper limb amputation: A longitudinal study , 2008, Neuroscience.

[25]  M. Jeannerod,et al.  Impaired Visual Hand Recognition in Preoperative Patients during Brachial Plexus Anesthesia: Importance of Peripheral Neural Input for Mental Representation of the Hand , 2011, Anesthesiology.

[26]  Kevin N. Ochsner,et al.  Attention and emotion: Does rating emotion alter neural responses to amusing and sad films? , 2005, NeuroImage.

[27]  K. Hagberg,et al.  Osseointegrated trans-femoral amputation prostheses: Prospective results of general and condition-specific quality of life in 18 patients at 2-year follow-up , 2008, Prosthetics and orthotics international.

[28]  K. Craig,et al.  Social modeling influences on sensory decision theory and psychophysiological indexes of pain. , 1978, Journal of personality and social psychology.

[29]  P. Halligan,et al.  Contralateral stimulation, using TENS, of phantom limb pain: two confirmatory cases. , 2010, Pain medicine.

[30]  Thomas Weiss,et al.  Decrease in phantom limb pain associated with prosthesis-induced increased use of an amputation stump in humans , 1999, Neuroscience Letters.

[31]  R. Melzack,et al.  Auricular transcutaneous electrical nerve stimulation (TENS) reduces phantom limb pain. , 1991, Journal of pain and symptom management.

[32]  I ROCK,et al.  Vision and Touch: An Experimentally Created Conflict between the Two Senses , 1964, Science.

[33]  Malcolm MacLachlan,et al.  Reaching with electricity: externally powered prosthetics and embodiment , 2004 .

[34]  Catherine Mercier,et al.  Training With Virtual Visual Feedback to Alleviate Phantom Limb Pain , 2009, Neurorehabilitation and neural repair.

[35]  Mark I. Johnson,et al.  Transcutaneous Electrical Nerve Stimulation for Phantom Pain and Stump Pain in Adult Amputees , 2013, Pain practice : the official journal of World Institute of Pain.

[36]  R. Melzack Pain and the neuromatrix in the brain. , 2001, Journal of dental education.

[37]  M. Tsakiris,et al.  Body-extension versus body-incorporation: Is there a need for a body-model? , 2009 .

[38]  O. Blanke,et al.  How vestibular stimulation interacts with illusory hand ownership , 2010, Consciousness and Cognition.

[39]  H. Flor,et al.  Effect of sensory discrimination training on cortical reorganisation and phantom limb pain , 2001, The Lancet.

[40]  J. Dostrovsky,et al.  Phantom sensations generated by thalamic microstimulation , 1998, Nature.

[41]  V. Cruz,et al.  Cortical remapping in amputees and dysmelic patients: a functional MRI study. , 2003, NeuroRehabilitation.

[42]  T. Riechert,et al.  Pain reduction in amputees by long-term spinal cord stimulation. Long-term follow-up study over 5 years. , 1980, Journal of neurosurgery.

[43]  Herta Flor,et al.  Mirrored, imagined and executed movements differentially activate sensorimotor cortex in amputees with and without phantom limb pain , 2010, PAIN®.

[44]  Katja Wiech,et al.  Tactile discrimination, but not tactile stimulation alone, reduces chronic limb pain , 2008, PAIN®.

[45]  T. Elbert,et al.  Phantom-limb pain as a perceptual correlate of cortical reorganization following arm amputation , 1995, Nature.

[46]  G. Carruthers Types of body representation and the sense of embodiment , 2008, Consciousness and Cognition.

[47]  Carla L. Harenski,et al.  Neural correlates of regulating negative emotions related to moral violations , 2006, NeuroImage.

[48]  Marco Molinari,et al.  The Sense of the Body in Individuals with Spinal Cord Injury , 2012, PloS one.

[49]  M. Hanley,et al.  Self-reported treatments used for lower-limb phantom pain: descriptive findings. , 2006, Archives of physical medicine and rehabilitation.

[50]  J C Rothwell,et al.  Reorganization of cortical blood flow and transcranial magnetic stimulation maps in human subjects after upper limb amputation. , 1994, Journal of neurophysiology.

[51]  A. Sirigu,et al.  Left and right hand recognition in upper limb amputees. , 2004, Brain : a journal of neurology.

[52]  G. Riet,et al.  Is placebo analgesia mediated by endogenous opioids? A systematic review , 1998, Pain.

[53]  A. Sirigu,et al.  Illusory movements of the paralyzed limb restore motor cortex activity , 2003, NeuroImage.

[54]  Jonathan D. Cohen,et al.  Rubber hands ‘feel’ touch that eyes see , 1998, Nature.

[55]  Jonathan Cole,et al.  On the immunity principle: a view from a robot , 2000, Trends in Cognitive Sciences.

[56]  Mukul Mukherjee,et al.  Medicine Meets Virtual Reality 14 , 2005 .

[57]  T. Aflalo,et al.  Mapping Behavioral Repertoire onto the Cortex , 2007, Neuron.

[58]  T. Jensen,et al.  A Randomized Study of the Effects of Gabapentin on Postamputation Pain , 2006, Anesthesiology.

[59]  F. Mast,et al.  Vestibular stimulation modifies the body schema , 2012, Neuropsychologia.

[60]  N Birbaumer,et al.  Reorganization of Motor and Somatosensory Cortex in Upper Extremity Amputees with Phantom Limb Pain , 2001, The Journal of Neuroscience.

[61]  S. Gallagher Philosophical conceptions of the self: implications for cognitive science , 2000, Trends in Cognitive Sciences.

[62]  Simon Crowle,et al.  Exploratory findings with virtual reality for phantom limb pain; from stump motion to agency and analgesia , 2009, Disability and rehabilitation.

[63]  V. Ramachandran,et al.  The perception of phantom limbs. The D. O. Hebb lecture. , 1998, Brain : a journal of neurology.

[64]  H. Henrik Ehrsson,et al.  Human Neuroscience , 2022 .

[65]  H. Flor Maladaptive plasticity, memory for pain and phantom limb pain: review and suggestions for new therapies , 2008, Expert review of neurotherapeutics.

[66]  J. Steurer,et al.  Journal of Neuroengineering and Rehabilitation Efficacy of Motor Imagery in Post-stroke Rehabilitation: a Systematic Review , 2022 .

[67]  P. Haggard,et al.  The balance of feelings: Vestibular modulation of bodily sensations , 2013, Cortex.

[68]  H. Flor,et al.  Targeting Cortical Representations in the Treatment of Chronic Pain , 2012, Neurorehabilitation and neural repair.

[69]  Katja Wiech,et al.  The effect of tactile discrimination training is enhanced when patients watch the reflected image of their unaffected limb during training , 2009, PAIN®.

[70]  Maria V. Sanchez-Vives,et al.  Towards a Digital Body: The Virtual Arm Illusion , 2008, Frontiers in human neuroscience.

[71]  Malcolm MacLachlan,et al.  Augmenting the Reality of Phantom Limbs: Three Case Studies Using an Augmented Mirror Box Procedure , 2006 .

[72]  K. Hagberg,et al.  One hundred patients treated with osseointegrated transfemoral amputation prostheses--rehabilitation perspective. , 2009, Journal of rehabilitation research and development.

[73]  Mark I. Johnson,et al.  Transcutaneous electrical nerve stimulation (TENS) for phantom pain and stump pain following amputation in adults. , 2015, The Cochrane database of systematic reviews.

[74]  Herta Flor,et al.  Sensorimotor training and cortical reorganization. , 2009, NeuroRehabilitation.

[75]  Nicola J. Ray,et al.  Abnormal thalamocortical dynamics may be altered by deep brain stimulation: Using magnetoencephalography to study phantom limb pain , 2009, Journal of Clinical Neuroscience.

[76]  Alexander L Green,et al.  Long-term outcomes of deep brain stimulation for neuropathic pain. , 2013, Neurosurgery.

[77]  O. Witte,et al.  Sensory feedback prosthesis reduces phantom limb pain: Proof of a principle , 2012, Neuroscience Letters.

[78]  Robert Bogue,et al.  Exoskeletons and robotic prosthetics: a review of recent developments , 2009, Ind. Robot.

[79]  M. Jeannerod,et al.  Mental imaging of motor activity in humans , 1999, Current Opinion in Neurobiology.

[80]  Toby Howard,et al.  The treatment of phantom limb pain using immersive virtual reality: Three case studies , 2007, Disability and rehabilitation.

[81]  Henrik Foltys,et al.  Repetitive transcranial magnetic stimulation of the parietal cortex transiently ameliorates phantom limb pain-like syndrome , 2003, Clinical Neurophysiology.

[82]  Kenneth M Heilman,et al.  Mirror therapy for phantom limb pain. , 2007, The New England journal of medicine.

[83]  N. Birbaumer,et al.  Does use of a myoelectric prosthesis prevent cortical reorganization and phantom limb pain? , 1999, Nature Neuroscience.

[84]  H. Ehrsson,et al.  Upper limb amputees can be induced to experience a rubber hand as their own , 2008, Brain : a journal of neurology.

[85]  Herta Flor,et al.  Phantom-limb pain: characteristics, causes, and treatment , 2002, The Lancet Neurology.

[86]  A. Young,et al.  Task instructions modulate neural responses to fearful facial expressions , 2003, Biological Psychiatry.

[87]  X. Navarro,et al.  Neural plasticity after peripheral nerve injury and regeneration , 2007, Progress in Neurobiology.

[88]  V. Busch,et al.  Phantom limb pain in daily practice--still a lot of work to do! , 2012, Pain medicine.

[89]  T. Metzinger,et al.  Video Ergo Sum: Manipulating Bodily Self-Consciousness , 2007, Science.

[90]  T. Nurmikko,et al.  Phantom limb pain, cortical reorganization and the therapeutic effect of mental imagery , 2008, Brain : a journal of neurology.

[91]  H. Flor,et al.  Phantom movements and pain. An fMRI study in upper limb amputees. , 2001, Brain : a journal of neurology.

[92]  Ronald Melzack,et al.  Pain: Past, Present, and Future , 1993 .

[93]  V. Ramachandran,et al.  Touching the phantom limb , 1995, Nature.