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Sparling T, Iyer L, Pasquina P, Petrus E. Cortical Reorganization after Limb Loss: Bridging the Gap between Basic Science and Clinical Recovery. J Neurosci 2024; 44:e1051232024. [PMID: 38171645 PMCID: PMC10851691 DOI: 10.1523/jneurosci.1051-23.2023] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/08/2023] [Revised: 08/28/2023] [Accepted: 09/29/2023] [Indexed: 01/05/2024] Open
Abstract
Despite the increasing incidence and prevalence of amputation across the globe, individuals with acquired limb loss continue to struggle with functional recovery and chronic pain. A more complete understanding of the motor and sensory remodeling of the peripheral and central nervous system that occurs postamputation may help advance clinical interventions to improve the quality of life for individuals with acquired limb loss. The purpose of this article is to first provide background clinical context on individuals with acquired limb loss and then to provide a comprehensive review of the known motor and sensory neural adaptations from both animal models and human clinical trials. Finally, the article bridges the gap between basic science researchers and clinicians that treat individuals with limb loss by explaining how current clinical treatments may restore function and modulate phantom limb pain using the underlying neural adaptations described above. This review should encourage the further development of novel treatments with known neurological targets to improve the recovery of individuals postamputation.Significance Statement In the United States, 1.6 million people live with limb loss; this number is expected to more than double by 2050. Improved surgical procedures enhance recovery, and new prosthetics and neural interfaces can replace missing limbs with those that communicate bidirectionally with the brain. These advances have been fairly successful, but still most patients experience persistent problems like phantom limb pain, and others discontinue prostheses instead of learning to use them daily. These problematic patient outcomes may be due in part to the lack of consensus among basic and clinical researchers regarding the plasticity mechanisms that occur in the brain after amputation injuries. Here we review results from clinical and animal model studies to bridge this clinical-basic science gap.
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Affiliation(s)
- Tawnee Sparling
- Department of Physical Medicine and Rehabilitation, Uniformed Services University of the Health Sciences, Bethesda, Maryland 20814
| | - Laxmi Iyer
- Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, Maryland 20817
| | - Paul Pasquina
- Department of Physical Medicine and Rehabilitation, Uniformed Services University of the Health Sciences, Bethesda, Maryland 20814
| | - Emily Petrus
- Department of Anatomy, Physiology and Genetics, Uniformed Services University, Bethesda, Maryland 20814
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Knorst GRS, Souza PRD, Araújo AGPD, Knorst SAF, Diniz DS, Filho HFDS. Transcranial magnetic stimulation in the treatment of phantom limb pain: a systematic review. ARQUIVOS DE NEURO-PSIQUIATRIA 2024; 82:1-10. [PMID: 38286434 PMCID: PMC10824589 DOI: 10.1055/s-0044-1779051] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/06/2023] [Accepted: 10/07/2023] [Indexed: 01/31/2024]
Abstract
BACKGROUND Phantom limb pain (PLP) occurs after amputations and can persist in a chronic and debilitating way. Repetitive transcranial magnetic stimulation (rTMS) is a non-invasive neuromodulation method capable of influencing brain function and modulating cortical excitability. Its effectiveness in treating chronic pain is promising. OBJECTIVE To evaluate the evidence on the efficacy and safety of using rTMS in the treatment of PLP, observing the stimulation parameters used, side effects, and benefits of the therapy. METHODS This is a systematic review of scientific articles published in national and international literature using electronic platforms. RESULTS Two hundred and fifty two articles were identified. Two hundred and forty six publications were removed because they were duplicated or met the exclusion criteria. After selection, six studies were reviewed, those being two randomized clinical trials and four case reports. All evaluated studies indicated some degree of benefit of rTMS to relieve painful symptoms, even temporarily. Pain perception was lower at the end of treatment when compared to the period prior to the sessions and remained during patient follow-up. There was no standardization of the stimulation parameters used. There were no reports of serious adverse events. The effects of long-term therapy have not been evaluated. CONCLUSION There are some benefits, even if temporary, in the use of rTMS to relieve painful symptoms in PLP. High-frequency stimulation at M1 demonstrated a significant analgesic effect. Given the potential that has been demonstrated, but limited by the paucity of high-quality studies, further controlled studies are needed to establish and standardize the clinical use of the method.
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Affiliation(s)
| | - Phamella Rocha de Souza
- Universidade Federal de Goiás, Hospital das Clínicas, Departamento de Neurologia, Goiânia GO, Brazil.
| | | | | | - Denise Sisterolli Diniz
- Universidade Federal de Goiás, Hospital das Clínicas, Departamento de Neurologia, Goiânia GO, Brazil.
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Tang VM, Ibrahim C, Rodak T, Goud R, Blumberger DM, Voineskos D, Le Foll B. Managing substance use in patients receiving therapeutic repetitive transcranial magnetic stimulation: A scoping review. Neurosci Biobehav Rev 2023; 155:105477. [PMID: 38007879 DOI: 10.1016/j.neubiorev.2023.105477] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/25/2023] [Revised: 11/16/2023] [Accepted: 11/18/2023] [Indexed: 11/28/2023]
Abstract
Repetitive Transcranial Magnetic Stimulation (rTMS) is an invaluable treatment option for neuropsychiatric disorders. Co-occurring recreational and nonmedical substance use can be common in those presenting for rTMS treatment, and it is unknown how it may affect the safety and efficacy of rTMS for the treatment of currently approved neuropsychiatric indications. This scoping review aimed to map the literature on humans receiving rTMS and had a history of any type of substance use. The search identified 274 articles providing information on inclusion/exclusion criteria, withdrawal criteria, safety protocols, type of rTMS and treatment parameters, adverse events and effect on primary outcomes that related to substance use. There are neurophysiological effects of substance use on cortical excitability, although the relevance to clinical rTMS practice is unknown. The current literature supports the safety and feasibility of delivering rTMS to those who have co-occurring neuropsychiatric disorder and substance use. However, specific details on how varying degrees of substance use alters the safety, efficacy, and mechanisms of rTMS remains poorly described.
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Affiliation(s)
- Victor M Tang
- Addictions Division, Centre for Addiction and Mental Health, Canada; Institute for Medical Science, Temerty Faculty of Medicine, University of Toronto, Canada; Department of Psychiatry, Temerty Faculty of Medicine, University of Toronto, Canada; Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Canada; Institute of Mental Health Policy Research, Centre for Addiction and Mental Health, Canada.
| | - Christine Ibrahim
- Addictions Division, Centre for Addiction and Mental Health, Canada; Institute for Medical Science, Temerty Faculty of Medicine, University of Toronto, Canada
| | - Terri Rodak
- CAMH Mental Health Sciences Library, Department of Education, Centre for Addiction and Mental Health, Canada
| | - Rachel Goud
- Addictions Division, Centre for Addiction and Mental Health, Canada
| | - Daniel M Blumberger
- Institute for Medical Science, Temerty Faculty of Medicine, University of Toronto, Canada; Department of Psychiatry, Temerty Faculty of Medicine, University of Toronto, Canada; Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Canada; Temerty Centre for Therapeutic Brain Intervention, Centre for Addiction and Mental Health, Canada
| | - Daphne Voineskos
- Institute for Medical Science, Temerty Faculty of Medicine, University of Toronto, Canada; Department of Psychiatry, Temerty Faculty of Medicine, University of Toronto, Canada; Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Canada; Temerty Centre for Therapeutic Brain Intervention, Centre for Addiction and Mental Health, Canada; Poul Hansen Family Centre for Depression, Krembil Research Institute, Toronto Western Hospital, University Health Network, Canada
| | - Bernard Le Foll
- Addictions Division, Centre for Addiction and Mental Health, Canada; Institute for Medical Science, Temerty Faculty of Medicine, University of Toronto, Canada; Department of Psychiatry, Temerty Faculty of Medicine, University of Toronto, Canada; Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Canada; Institute of Mental Health Policy Research, Centre for Addiction and Mental Health, Canada; CAMH Mental Health Sciences Library, Department of Education, Centre for Addiction and Mental Health, Canada; Temerty Centre for Therapeutic Brain Intervention, Centre for Addiction and Mental Health, Canada; Poul Hansen Family Centre for Depression, Krembil Research Institute, Toronto Western Hospital, University Health Network, Canada; Department of Pharmacology and Toxicology, Temerty Faculty of Medicine, University of Toronto, Canada; Department of Family and Community Medicine, Temerty Faculty of Medicine, University of Toronto, Canada; Waypoint Research Institute, Waypoint Centre for Mental Health Care, Penetanguishene, Canada
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de Jongh Curry AL, Hunt ME, Pasquina PF, Waters RS, Tsao JW. Non-surgical Management of Phantom Limb Pain: Current and Emerging Clinical Approaches. CURRENT PHYSICAL MEDICINE AND REHABILITATION REPORTS 2023. [DOI: 10.1007/s40141-023-00377-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/06/2023]
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DaSilva AF, Datta A, Swami J, Kim DJ, Patil PG, Bikson M. The Concept, Development, and Application of a Home-Based High-Definition tDCS for Bilateral Motor Cortex Modulation in Migraine and Pain. FRONTIERS IN PAIN RESEARCH 2022; 3:798056. [PMID: 35295794 PMCID: PMC8915734 DOI: 10.3389/fpain.2022.798056] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/19/2021] [Accepted: 01/13/2022] [Indexed: 11/16/2022] Open
Abstract
Whereas, many debilitating chronic pain disorders are dominantly bilateral (e.g., fibromyalgia, chronic migraine), non-invasive and invasive cortical neuromodulation therapies predominantly apply unilateral stimulation. The development of excitatory stimulation targeting bilateral primary motor (M1) cortices could potentially expand its therapeutic effect to more global pain relief. However, this is hampered by increased procedural and technical complexity. For example, repetitive transcranial magnetic stimulation (rTMS) and 4 × 1/2 × 2 high-definition transcranial direct current stimulation (4 × 1/2 × 2 HD-tDCS) are largely center-based, with unilateral-target focus-bilateral excitation would require two rTMS/4 × 1 HD-tDCS systems. We developed a system that allows for focal, non-invasive, self-applied, and simultaneous bilateral excitatory M1 stimulation, supporting long-term home-based treatment with a well-tolerated wearable battery-powered device. Here, we overviewed the most employed M1 neuromodulation methods, from invasive techniques to non-invasive TMS and tDCS. The evaluation extended from non-invasive diffuse asymmetric bilateral (M1-supraorbital [SO] tDCS), non-invasive and invasive unilateral focal (4 × 1/2 × 2 HD-tDCS, rTMS, MCS), to non-invasive and invasive bilateral bipolar (M1-M1 tDCS, MCS), before outlining our proposal for a neuromodulatory system with unique features. Computational models were applied to compare brain current flow for current laboratory-based unilateral M11 and bilateral M12 HD-tDCS models with a functional home-based M11-2 HD-tDCS prototype. We concluded the study by discussing the promising concept of bilateral excitatory M1 stimulation for more global pain relief, which is also non-invasive, focal, and home-based.
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Affiliation(s)
- Alexandre F. DaSilva
- Headache and Orofacial Pain Effort Lab, Department of Biologic and Materials Sciences and Prosthodontics, University of Michigan School of Dentistry, Ann Arbor, MI, United States
| | | | - Jaiti Swami
- Neural Engineering Laboratory, Department of Biomedical Engineering, The City College of New York, New York, NY, United States
| | - Dajung J. Kim
- Headache and Orofacial Pain Effort Lab, Department of Biologic and Materials Sciences and Prosthodontics, University of Michigan School of Dentistry, Ann Arbor, MI, United States
| | - Parag G. Patil
- Department of Neurosurgery, University of Michigan, Ann Arbor, MI, United States
- Department of Neurology, University of Michigan, Ann Arbor, MI, United States
- Department of Biomedical Engineering, University of Michigan, Ann Arbor, MI, United States
- Department of Anesthesiology, University of Michigan, Ann Arbor, MI, United States
| | - Marom Bikson
- Neural Engineering Laboratory, Department of Biomedical Engineering, The City College of New York, New York, NY, United States
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Abstract
Symptomatic neuromas and chronic neuropathic pain are significant problems affecting patients' quality of life and independence that are challenging to treat. These symptoms are due to structural and functional changes that occur peripherally within neuromas, as well as alterations that occur centrally within the brain and spinal cord. A multimodal approach is most effective, with goals to minimize opioid use, to capitalize on the synergistic effects of nonopioid medications and to explore potential benefits of novel adjunctive treatments.
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Affiliation(s)
- Yusha Liu
- Department of Surgery, University of Washington, 325 9th Avenue, 7 CT 70, MS 359796, Seattle, WA 98104, USA
| | - Dennis S Kao
- Department of Surgery, University of Washington, 325 9th Avenue, 7 CT 70, MS 359796, Seattle, WA 98104, USA.
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Zhang KL, Yuan H, Wu FF, Pu XY, Liu BZ, Li Z, Li KF, Liu H, Yang Y, Wang YY. Analgesic Effect of Noninvasive Brain Stimulation for Neuropathic Pain Patients: A Systematic Review. Pain Ther 2021; 10:315-332. [PMID: 33751453 PMCID: PMC8119533 DOI: 10.1007/s40122-021-00252-1] [Citation(s) in RCA: 19] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/24/2020] [Accepted: 02/26/2021] [Indexed: 01/04/2023] Open
Abstract
Introduction The objective of this review is to systematically summarize the consensus on best practices for different NP conditions of the two most commonly utilized noninvasive brain stimulation (NIBS) technologies, repetitive transcranial magnetic stimulation (rTMS), and transcranial direct current stimulation (tDCS). Methods PubMed was searched according to the predetermined keywords and criteria. Only English language studies and studies published up to January 31, 2020 were taken into consideration. Meta-analyses, reviews, and systematic reviews were excluded first, and those related to animal studies or involving healthy volunteers were also excluded. Finally, 29 studies covering 826 NP patients were reviewed. Results The results from the 24 enrolled studies and 736 NP patients indicate that rTMS successfully relieved the pain symptoms of 715 (97.1%) NP patients. Also, five studies involving 95 NP patients (81.4%) also showed that tDCS successfully relieved NP. In the included studied, the M1 region plays a key role in the analgesic treatment of NIBS. The motor evoked potentials (MEPs), the 10–20 electroencephalography system (EEG 10/20 system), and neuro-navigation methods are used in clinical practice to locate therapeutic targets. Based on the results of the review, the stimulation parameters of rTMS that best induce an analgesic effect are a stimulation frequency of 10–20 Hz, a stimulation intensity of 80–120% of RMT, 1000–2000 pulses, and 5–10 sessions, and the most effective parameters of tDCS are a current intensity of 2 mA, a session duration of 20–30 min, and 5–10 sessions. Conclusions Our systematically reviewed the evidence for positive and negative responses to rTMS and tDCS for NP patient care and underscores the analgesic efficacy of NIBS in patients with NP. The treatment of NP should allow the design of optimal treatments for individual patients.
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Affiliation(s)
- Kun-Long Zhang
- Specific Lab for Mitochondrial Plasticity Underlying Nervous System Diseases, National Demonstration Center for Experimental Preclinical Medicine Education, Air Force Medical University, Xi'an, 710032, China.,Department of Rehabilitation Medicine, Xi-Jing Hospital, Air Force Medical University, Xi'an, 710032, China
| | - Hua Yuan
- Department of Rehabilitation Medicine, Xi-Jing Hospital, Air Force Medical University, Xi'an, 710032, China
| | - Fei-Fei Wu
- Specific Lab for Mitochondrial Plasticity Underlying Nervous System Diseases, National Demonstration Center for Experimental Preclinical Medicine Education, Air Force Medical University, Xi'an, 710032, China
| | - Xue-Yin Pu
- Specific Lab for Mitochondrial Plasticity Underlying Nervous System Diseases, National Demonstration Center for Experimental Preclinical Medicine Education, Air Force Medical University, Xi'an, 710032, China
| | - Bo-Zhi Liu
- Specific Lab for Mitochondrial Plasticity Underlying Nervous System Diseases, National Demonstration Center for Experimental Preclinical Medicine Education, Air Force Medical University, Xi'an, 710032, China
| | - Ze Li
- Specific Lab for Mitochondrial Plasticity Underlying Nervous System Diseases, National Demonstration Center for Experimental Preclinical Medicine Education, Air Force Medical University, Xi'an, 710032, China
| | - Kai-Feng Li
- Specific Lab for Mitochondrial Plasticity Underlying Nervous System Diseases, National Demonstration Center for Experimental Preclinical Medicine Education, Air Force Medical University, Xi'an, 710032, China
| | - Hui Liu
- Specific Lab for Mitochondrial Plasticity Underlying Nervous System Diseases, National Demonstration Center for Experimental Preclinical Medicine Education, Air Force Medical University, Xi'an, 710032, China.,Department of Human Anatomy, Yan-An University, Yan'an, 716000, China
| | - Yi Yang
- Specific Lab for Mitochondrial Plasticity Underlying Nervous System Diseases, National Demonstration Center for Experimental Preclinical Medicine Education, Air Force Medical University, Xi'an, 710032, China.,Department of Human Anatomy, Yan-An University, Yan'an, 716000, China
| | - Ya-Yun Wang
- Specific Lab for Mitochondrial Plasticity Underlying Nervous System Diseases, National Demonstration Center for Experimental Preclinical Medicine Education, Air Force Medical University, Xi'an, 710032, China. .,State Key Laboratory of Military Stomatology, School of Stomatology, The Fourth Military Medical University, Xi'an, China.
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Aamir A, Girach A, Sarrigiannis PG, Hadjivassiliou M, Paladini A, Varrassi G, Zis P. Repetitive Magnetic Stimulation for the Management of Peripheral Neuropathic Pain: A Systematic Review. Adv Ther 2020; 37:998-1012. [PMID: 31989485 DOI: 10.1007/s12325-020-01231-2] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/27/2019] [Indexed: 02/07/2023]
Abstract
INTRODUCTION Repetitive magnetic stimulation (rMS) is a safe and well-tolerated intervention. Transcranial magnetic stimulation (TMS) is used for the treatment of depression and for the treatment and prevention of migraine. Over the last few years, several reports and randomised controlled studies of the use of rMS for the treatment of pain have been published. The aim of this systematic review was to identify the available literature regarding the use of rMS in the treatment of peripheral neuropathic pain. METHODS After a systematic Medline search we identified 12 papers eligible to be included in this review. RESULTS The majority of the studies were on patients with phantom limb pain, followed by radiculopathy, plexopathy, post-traumatic pain and peripheral neuropathy. The treatment protocols vary significantly from study to study and, therefore, pooling the results together is currently difficult. However, rMS has a definite immediate effect in pain relief which, in the majority of studies, is maintained for a few weeks. CONCLUSION rMS seems to be a promising intervention in the treatment of peripheral neuropathic pain. Further research is in the field is needed. Use of neuronavigation might increase the precision of stimulation and subsequently its effectiveness.
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Affiliation(s)
| | - Ayesha Girach
- Medical School, University of Sheffield, Sheffield, UK
| | | | - Marios Hadjivassiliou
- Academic Directorate of Neurosciences, Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield, UK
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Yang S, Chang MC. Effect of Repetitive Transcranial Magnetic Stimulation on Pain Management: A Systematic Narrative Review. Front Neurol 2020; 11:114. [PMID: 32132973 PMCID: PMC7040236 DOI: 10.3389/fneur.2020.00114] [Citation(s) in RCA: 81] [Impact Index Per Article: 16.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/24/2019] [Accepted: 01/31/2020] [Indexed: 12/17/2022] Open
Abstract
Recently, clinicians have been using repetitive transcranial magnetic stimulation (rTMS) for treating various pain conditions. This systematic narrative review aimed to examine the use and efficacy of rTMS for controlling various pain conditions. A PubMed search was conducted for articles that were published until June 7, 2019 and used rTMS for pain alleviation. The key search phrase for identifying potentially relevant articles was (repetitive transcranial magnetic stimulation AND pain). The following inclusion criteria were applied for article selection: (1) patients with pain, (2) rTMS was applied for pain management, and (3) follow-up evaluations were performed after rTMS stimulation to assess the reduction in pain. Review articles were excluded. Overall, 1,030 potentially relevant articles were identified. After reading the titles and abstracts and assessing eligibility based on the full-text articles, 106 publications were finally included in our analysis. Overall, our findings suggested that rTMS is beneficial for treating neuropathic pain of various origins, such as central pain, pain from peripheral nerve disorders, fibromyalgia, and migraine. Although data on the use of rTMS for orofacial pain, including trigeminal neuralgia, phantom pain, low back pain, myofascial pain syndrome, pelvic pain, and complex regional pain syndrome, were promising, there was insufficient evidence to determine the efficacy of rTMS for treating these conditions. Therefore, further studies are needed to validate the effects of rTMS on pain relief in these conditions. Overall, this review will help guide clinicians in making informed decisions regarding whether rTMS is an appropriate option for managing various pain conditions.
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Affiliation(s)
- Seoyon Yang
- Department of Rehabilitation Medicine, Ewha Woman's University Seoul Hospital, Ewha Woman's University School of Medicine, Seoul, South Korea
| | - Min Cheol Chang
- Department of Rehabilitation Medicine, College of Medicine, Yeungnam University, Daegu, South Korea
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Lu YS, Tong P, Guo TC, Ding XH, Zhang S, Zhang XJ. Effects of combined rTMS and visual feedback on the rehabilitation of supernumerary phantom limbs in a patient with spinal cord injury: A case report. World J Clin Cases 2019; 7:3120-3125. [PMID: 31624763 PMCID: PMC6795722 DOI: 10.12998/wjcc.v7.i19.3120] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/29/2019] [Revised: 08/24/2019] [Accepted: 09/11/2019] [Indexed: 02/05/2023] Open
Abstract
BACKGROUND Supernumerary phantom limb (SPL) caused by spinal cord injury (SCI) has previously been reported in several studies. However, the mechanisms and management of SPL in SCI patients are still not fully understood. Herein, we report a rare case of SPL in a patient with incomplete SCI.
CASE SUMMARY A 46-year-old man complained of four hands 7 d after SCI. He was diagnosed with SPL complicated with actual limb neuropathic pain. Following a period of treatment with neurotrophic agents and Chinese traditional and analgesic medications, SPL symptoms and actual limb pain did not improve. However, his symptoms gradually lessened after combined treatment with high-frequency repetitive transcranial magnetic stimulation (rTMS), a promising neuromodulation technique, over the M1 cortex and visual feedback. After 7 wk of this treatment, SPL disappeared completely and actual limb pain was significantly relieved.
CONCLUSION Cerebral plasticity changes may be a mechanism underlying the occurrence of non-painful SPL in SCI patients, and high-frequency rTMS applied to the M1 cortex could be a promising treatment method for SPL.
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Affiliation(s)
- Yin-Shan Lu
- Department of Rehabilitation Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei Province, China
- Department of Rehabilitation Medicine, Renmin Hospital of Wuhan University, Wuhan 430060, Hubei Province, China
| | - Pei Tong
- Department of Rehabilitation Medicine, Taikang Tongji (Wuhan) Hospital, Wuhan 430000, Hubei Province, China
| | - Tie-Cheng Guo
- Department of Rehabilitation Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei Province, China
| | - Xin-Hua Ding
- Department of Rehabilitation Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei Province, China
| | - Song Zhang
- Department of Rehabilitation Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei Province, China
| | - Xiu-Juan Zhang
- Department of Rehabilitation Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei Province, China
- Department of Rehabilitation Medicine, Chengdu Second People's Hospital, Chengdu 610011, Sichuan Province, China
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Abstract
Phantom limb pain is a chronic neuropathic pain that develops in 45-85% of patients who undergo major amputations of the upper and lower extremities and appears predominantly during two time frames following an amputation: the first month and later about 1 year. Although in most patients the frequency and intensity of pain diminish over time, severe pain persists in about 5-10%. It has been proposed that factors in both the peripheral and central nervous systems play major roles in triggering the development and maintenance of pain associated with extremity amputations. Chronic pain is physically and mentally debilitating, affecting an individual's capacity for self-care, but also diminishing an individual's daily capacity for personal and economic independence. In addition, the pain may lead to depression and feelings of hopelessness. A National Center for Biotechnology Information study found that in the USA alone, the annual cost of dealing with neuropathic pain is more than $600 billion, with an estimated 20 million people in the USA suffering from this condition. Although the pain can be reduced by antiepileptic drugs and analgesics, they are frequently ineffective or their side effects preclude their use. The optimal approach for eliminating neuropathic pain and improving individuals' quality of life is the development of novel techniques that permanently prevent the development and maintenance of neuropathic pain, or that eliminate the pain once it has developed. What is still required is understanding when and where an effective novel technique must be applied, such as onto the nerve stump of the transected peripheral axons, dorsal root ganglion neurons, spinal cord, or cortex to induce the desired influences. This review, the second of two in this journal volume, examines the techniques that may be capable of reducing or eliminating chronic neuropathic pain once it has developed. Such an understanding will improve amputees' quality of life by blocking the mechanisms that trigger and/or maintain PLP and chronic neuropathic pain.
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Affiliation(s)
- Damien P Kuffler
- Institute of Neurobiology, University of Puerto Rico, Medical Science Campus, 201 Blvd. del Valle, San Juan, PR, 00901, Puerto Rico.
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Nardone R, Versace V, Sebastianelli L, Brigo F, Christova M, Scarano GI, Saltuari L, Trinka E, Hauer L, Sellner J. Transcranial magnetic stimulation in subjects with phantom pain and non-painful phantom sensations: A systematic review. Brain Res Bull 2019; 148:1-9. [DOI: 10.1016/j.brainresbull.2019.03.001] [Citation(s) in RCA: 24] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/13/2019] [Revised: 03/03/2019] [Accepted: 03/05/2019] [Indexed: 12/18/2022]
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Petersen BA, Nanivadekar AC, Chandrasekaran S, Fisher LE. Phantom limb pain: peripheral neuromodulatory and neuroprosthetic approaches to treatment. Muscle Nerve 2018; 59:154-167. [DOI: 10.1002/mus.26294] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 07/01/2018] [Indexed: 12/11/2022]
Affiliation(s)
- Bailey A. Petersen
- Department of Bioengineering; University of Pittsburgh; 3520 Fifth Avenue, Pittsburgh Pennsylvania 15213 USA
| | - Ameya C. Nanivadekar
- Department of Bioengineering; University of Pittsburgh; 3520 Fifth Avenue, Pittsburgh Pennsylvania 15213 USA
| | - Santosh Chandrasekaran
- Department of Physical Medicine and Rehabilitation; University of Pittsburgh; Pittsburgh Pennsylvania USA
| | - Lee E. Fisher
- Department of Bioengineering; University of Pittsburgh; 3520 Fifth Avenue, Pittsburgh Pennsylvania 15213 USA
- Department of Physical Medicine and Rehabilitation; University of Pittsburgh; Pittsburgh Pennsylvania USA
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Noninvasive neuromodulation techniques for the management of phantom limb pain: a systematic review of randomized controlled trials. Int J Rehabil Res 2018; 42:1-10. [PMID: 30222617 DOI: 10.1097/mrr.0000000000000317] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/17/2023]
Abstract
Neuromodulation techniques work by modulating pain perception by inducing changes in polarity of the neuronal membrane and thereby cortical excitability. The aim of this review is to evaluate the efficiency and safety of noninvasive neuromodulation techniques for phantom limb pain (PLP). A systematic literature search in the PubMed, Scopus, Web of Science, and Cochrane Library databases was performed to identify studies investigating the effects of noninvasive neuromodulation for PLP. The included journal articles were assessed with Furlan et al.'s method for examining the risk of bias to assess methodologic quality, and evidence was graded using the GRADE approach. The literature search identified 239 studies. Of these 239, four studies fulfilled the inclusion criteria and were included for data extraction. Two of the studies focused on repetitive transcranial magnetic stimulation (rTMS) whereas two other concentrated on transcranial direct current stimulation (tDCS). The present review showed that there is conflicting evidence to support the use of tDCS in short term and moderate evidence to support the use of rTMS in immediate and short term. It is important to recognize that this evidence comes from a very small sample size. No serious adverse effects were reported. Further information from randomized controlled trials with larger sample size investigating immediate and short-term and long-term effects are needed to clarify the best effective stimulation parameters and number of sessions of tDCS and rTMS for PLP.
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Morales-Quezada L. Noninvasive Brain Stimulation, Maladaptive Plasticity, and Bayesian Analysis in Phantom Limb Pain. Med Acupunct 2017; 29:220-228. [PMID: 28874923 DOI: 10.1089/acu.2017.1240] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/28/2022] Open
Abstract
Introduction: Phantom limb pain (PLP) is a common and poorly understood pathology of difficult medical control that progressively takes place after amputation occurs. Objective: This article discusses the multifactorial bases of PLP. These bases involve local changes at the stump level, spinal modifications of excitability, deafferentation, and central sensitization, leading to the development of maladaptive plasticity, and consequentially, defective processing of sensory information by associative neural networks. These changes can be traced by neurophysiology and imaging topographical studies, indicating a degree of cortical reorganization that perpetuates pain and discomfort. Intervention: Noninvasive brain stimulation can be an alternative way to manage PLP. This article discusses two techniques-transcranial direct current stimulation (tDCS) and repetitive transcranial magnetic stimulation (rTMS)-that have shown promising results for controlling PLP. The modulation that both techniques rely on is based on synaptic mechanisms linked to long-term potentiation and long-term depression phenomena. By applying tDCS or rTMS, clinicians can target processes associated with central sensitization and maladaptive plasticity, while promoting adequate sensory information processing by integrative cognitive behavioral techniques in a comprehensive rehabilitation program. Conclusions: Understanding PLP from a dynamic neurocomputational perspective will help to develop better treatments. Furthermore, Bayesian analysis of sensory information can help guide and monitor therapeutic interventions directed toward PLP resolution.
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Affiliation(s)
- Leon Morales-Quezada
- Neuromodulation Laboratory, Spaulding Neuromodulation Center, Spaulding Rehabilitation Hospital, Harvard Medical School, Boston, MA.,Division of General Medicine and Primary Care, Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA
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Taheri A, Lajevardi M, Arab S, Firouzian A, Sharifi H. Repetitive Transcranial Magnetic Stimulation for Phantom Limb Pain: Probably Effective but Understudied. Neuromodulation 2017; 20:88-89. [PMID: 28101993 DOI: 10.1111/ner.12569] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/21/2022]
Affiliation(s)
- Arman Taheri
- Department of Anesthesiology and Pain Medicine, Imam Khomeini Hospital, Tehran University of Medical Sciences, Tehran, Iran
| | - Mahbod Lajevardi
- Department of Anesthesiology and Pain Medicine, Imam Khomeini Hospital, Tehran University of Medical Sciences, Tehran, Iran
| | - Saghar Arab
- Department of Anesthesiology and Pain Medicine, Imam Khomeini Hospital, Tehran University of Medical Sciences, Tehran, Iran
| | - Abolfazl Firouzian
- Department of Anesthesiology and Pain Medicine, Imam Khomeini Hospital, Tehran University of Medical Sciences, Tehran, Iran.,Department of Anesthesiology, Faculty of Medicine, Mazandaran University of Medical Sciences, Sari, Iran
| | - Hassan Sharifi
- Department of Medical Surgical Nursing, School of Nursing and Midwifery, Iranshahr University of Medical Sciences, Iranshahr, Iran.,School of Nursing and Midwifery, Mashhad University of Medical Sciences, Mashhad, Iran
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Malavera A, Silva FA, Fregni F, Carrillo S, Garcia RG. Repetitive Transcranial Magnetic Stimulation for Phantom Limb Pain in Land Mine Victims: A Double-Blinded, Randomized, Sham-Controlled Trial. THE JOURNAL OF PAIN 2016; 17:911-8. [PMID: 27260638 PMCID: PMC4969102 DOI: 10.1016/j.jpain.2016.05.003] [Citation(s) in RCA: 65] [Impact Index Per Article: 7.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/08/2015] [Revised: 04/21/2016] [Accepted: 05/06/2016] [Indexed: 02/07/2023]
Abstract
UNLABELLED We evaluated the effects of repetitive transcranial magnetic stimulation (rTMS) in the treatment of phantom limb pain (PLP) in land mine victims. Fifty-four patients with PLP were enrolled in a randomized, double-blinded, placebo-controlled, parallel group single-center trial. The intervention consisted of real or sham rTMS of M1 contralateral to the amputated leg. rTMS was given in series of 20 trains of 6-second duration (54-second intertrain, intensity 90% of motor threshold) at a stimulation rate of 10 Hz (1,200 pulses), 20 minutes per day, during 10 days. For the control group, a sham coil was used. The administration of active rTMS induced a significantly greater reduction in pain intensity (visual analogue scale scores) 15 days after treatment compared with sham stimulation (-53.38 ± 53.12% vs -22.93 ± 57.16%; mean between-group difference = 30.44%, 95% confidence interval, .30-60.58; P = .03). This effect was not significant 30 days after treatment. In addition, 19 subjects (70.3%) attained a clinically significant pain reduction (>30%) in the active group compared with 11 in the sham group (40.7%) 15 days after treatment (P = .03). The administration of 10 Hz rTMS on the contralateral primary motor cortex for 2 weeks in traumatic amputees with PLP induced significant clinical improvement in pain. PERSPECTIVE High-frequency rTMS on the contralateral primary motor cortex of traumatic amputees induced a clinically significant pain reduction up to 15 days after treatment without any major secondary effect. These results indicate that rTMS is a safe and effective therapy in patients with PLP caused by land mine explosions.
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Affiliation(s)
- Alejandra Malavera
- Neurovascular Science Group, Fundación Cardiovascular de Colombia, Floridablanca, Colombia; Spaulding Neuromodulation Center, Spaulding Rehabilitation Hospital, Harvard Medical School, Boston, Massachusetts
| | - Federico Arturo Silva
- Neurovascular Science Group, Fundación Cardiovascular de Colombia, Floridablanca, Colombia
| | - Felipe Fregni
- Spaulding Neuromodulation Center, Spaulding Rehabilitation Hospital, Harvard Medical School, Boston, Massachusetts
| | - Sandra Carrillo
- Neurovascular Science Group, Fundación Cardiovascular de Colombia, Floridablanca, Colombia
| | - Ronald G Garcia
- Neurovascular Science Group, Fundación Cardiovascular de Colombia, Floridablanca, Colombia; MASIRA Research Institute, School of Medicine, Universidad de Santander, Bucaramanga, Colombia; Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts.
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Raffin E, Richard N, Giraux P, Reilly KT. Primary motor cortex changes after amputation correlate with phantom limb pain and the ability to move the phantom limb. Neuroimage 2016; 130:134-144. [DOI: 10.1016/j.neuroimage.2016.01.063] [Citation(s) in RCA: 73] [Impact Index Per Article: 8.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/26/2015] [Revised: 01/11/2016] [Accepted: 01/15/2016] [Indexed: 01/25/2023] Open
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Malavera Angarita MA, Carrillo Villa S, Gomezese Ribero OF, García RG, Silva Sieger FA. Pathophysiology and treatment of phantom limb pain. COLOMBIAN JOURNAL OF ANESTHESIOLOGY 2014. [DOI: 10.1016/j.rcae.2013.10.002] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/25/2022] Open
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Malavera Angarita MA, Carrillo Villa S, Gomezese Ribero OF, García RG, Silva Sieger FA. Fisiopatología y tratamiento del dolor de miembro fantasma. ACTA ACUST UNITED AC 2014. [DOI: 10.1016/j.rca.2013.09.012] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/30/2022]
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Use of Yamamoto New Scalp Acupuncture for Treatment of Chronic, Severe Phantom Leg Pain. Med Acupunct 2012. [DOI: 10.1089/acu.2011.0854] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/12/2022] Open
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Knotkova H, Cruciani RA, Tronnier VM, Rasche D. Current and future options for the management of phantom-limb pain. J Pain Res 2012; 5:39-49. [PMID: 22457600 PMCID: PMC3308715 DOI: 10.2147/jpr.s16733] [Citation(s) in RCA: 50] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/26/2022] Open
Abstract
Phantom-limb pain (PLP) belongs among difficult-to-treat chronic pain syndromes. Treatment options for PLP are to a large degree implicated by the level of understanding the mechanisms and nature of PLP. Research and clinical findings acknowledge the neuropathic nature of PLP and also suggest that both peripheral as well as central mechanisms, including neuroplastic changes in central nervous system, can contribute to PLP. Neuroimaging studies in PLP have indicated a relation between PLP and the neuroplastic changes. Further, it has been shown that the pathological neuroplastic changes could be reverted, and there is a parallel between an improvement (reversal) of the neuroplastic changes in PLP and pain relief. These findings facilitated explorations of novel neuromodulatory treatment strategies, adding to the variety of treatment approaches in PLP. Overall, available treatment options in PLP include pharmacological treatment, supportive non-pharmacological non-invasive strategies (eg, neuromodulation using transcranial magnetic stimulation, visual feedback therapy, or motor imagery; peripheral transcutaneous electrical nerve stimulation, physical therapy, reflexology, or various psychotherapeutic approaches), and invasive treatment strategies (eg, surgical destructive procedures, nerve blocks, or invasive neuromodulation using deep brain stimulation, motor cortex stimulation, or spinal cord stimulation). Venues of further development in PLP management include a technological and methodological improvement of existing treatment methods, an implementation of new techniques and products, and a development of new treatment approaches.
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Affiliation(s)
- Helena Knotkova
- Department of Pain Medicine and Palliative Care, Research Division, Institute for Non-invasive Brain Stimulation, Beth Israel Medical Center, New York, NY, USA
- Department of Neurology, Albert Einstein College of Medicine, Bronx, NY, USA
| | - Ricardo A Cruciani
- Department of Pain Medicine and Palliative Care, Research Division, Institute for Non-invasive Brain Stimulation, Beth Israel Medical Center, New York, NY, USA
- Department of Neurology, Albert Einstein College of Medicine, Bronx, NY, USA
- Department of Anesthesiology, Albert Einstein College of Medicine, Bronx, NY, USA
| | | | - Dirk Rasche
- Department of Neurosurgery, University of Lübeck, Germany
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