Repetitive Transcranial Magnetic Stimulation of the Dorsolateral Prefrontal Cortex for Phantom Limb Pain.

BACKGROUND: Phantom limb pain (PLP) is a prevalent and distressing occurrence in 60-80% of individuals who have undergone amputations. Recent research underscores the significance of maladaptive cortical plasticity in the genesis of PLP, emphasizing the importance of targeting cortical areas for therapeutic interventions. Repetitive transcranial magnetic stimulation (rTMS), a noninvasive tool for cortical stimulation, demonstrates effectiveness in treating various chronic pain conditions of neuropathic origin. Nevertheless, there exists a limited body of research investigating the application of rTMS as a therapeutic intervention specifically for managing PLP. Notably, the dorsolateral prefrontal cortex (DLPFC) plays a crucial role in central pain processing, suggesting its potential as a key therapeutic target in PLP treatment. There is a lack of adequate data regarding the effectiveness of DLPFC-targeting rTMS in alleviating the pain experienced by PLP patients. OBJECTIVE: In this study, our aim was to investigate the impact of 10 sessions of DLPFC-targeting rTMS on the pain status of individuals experiencing PLP. STUDY DESIGN: Randomized controlled trial. SETTING: Traumatic amputees reporting to the tertiary care center with PLP. METHODS: The study was approved by the Institute Ethics Committee (IECPG-299/27.04.2022) and registered in the Clinical Trials Registry of India (CTRI/2022/07/043938). Nineteen patients suffering from PLP were recruited and randomized into real or sham rTMS groups. In the real rTMS group, patients received 10 sessions of rTMS at the DLPFC contralateral to the amputation site. The rTMS, administered at 90% of the resting motor threshold (RMT), was delivered as 8 trains of 150 pulses per train at the rate of one Hz and an inter-train interval of 60 seconds. The total number of pulses per session was 1,200. The sham group received 10 sessions of sham rTMS through the perpendicular placement of an rTMS coil over the DLPFC. These sessions lasted for the same duration and included the same sounds as the real group but involved no active stimulation. The patients' pain status was evaluated using the Visual Analog Scale (VAS) at baseline, at the end of each session of real or sham rTMS and at the 15th, 30th, and 60th day after the the completion of real or sham therapy. RESULTS: A significant decrease in VAS scores was noted after 10 sessions of real rTMS that targeted the DLPFC, in contrast to the sham rTMS group. The real rTMS group's reduction in VAS scores also persisted during the follow-up. LIMITATIONS: A few patients had to drop out due to physical restrictions and financial constraints. Consequently, only a small number of individuals were able to complete the study protocol successfully. CONCLUSION: A regimen of 10 sessions of real rTMS of the DLPFC was associated with significant pain relief in patients with PLP, and the effects were sustained for 2 months. Therefore, the present study shows that rTMS of the DLPFC has potential as an effective therapeutic intervention for sustained pain relief in PLP patients.

Robotic-Enhanced Prosthetic Liners for Vibration Therapy: Reducing Phantom Limb Pain in Transfemoral Amputees.

Phantom limb pain, a common challenge for amputees, lacks effective treatment options. Vibration therapy is a promising non-pharmacologic intervention for reducing pain intensity, but its efficacy in alleviating phantom limb pain requires further investigation. This study focused on developing prosthesis liners with integrated vibration motors to administer vibration therapy for phantom limb pain. The prototypes developed for this study addressed previous issues with wiring the electronic components. Two transfemoral amputees participated in a four-week at-home trial, during which they used the vibration liner and rated their initial and final pain intensity on a numeric rating scale each time they had phantom pain. Semi-structured interviews were conducted to gather feedback following the at-home trial. Both participants described relaxing and soothing sensations in their residual limb and phantom limb while using vibration therapy. One participant reported a relaxation of his phantom limb sensations, while both participants noted a decrease in the intensity of their phantom limb pain. Participants said the vibration liners were comfortable but suggested that the vibration could be stronger and that aligning the contacts could be easier. The results of this study highlight the potential effectiveness of using vibration therapy to reduce the intensity of phantom limb pain and suggest a vibration liner may be a feasible mode of administering the therapy. Future research should address optimizing the performance of the vibration liners to maximize their therapeutic benefits.

Mesenchymal Stem Cell Engagement Modulates Neuroma Microenviroment in Rats and Humans and Prevents Postamputation Pain.

Postamputation pain is currently managed unsatisfactorily with neuron-targeted pharmacological and interventional therapies. Non-neuronal pain mechanisms have emerged as crucial factors in the development and persistence of postamputation pain. Consequently, these mechanisms offer exciting prospects as innovative therapeutic targets. We examined the hypothesis that engaging mesenchymal stem cells (MSCs) would foster local neuroimmune interactions, leading to a potential reduction in postamputation pain. We utilized an ex vivo neuroma model from a phantom limb pain patient to uncover that the oligodeoxynucleotide IMT504 engaged human primary MSCs to promote an anti-inflammatory microenvironment. Reverse translation experiments recapitulated these effects. Thus, in an in vivo rat model, IMT504 exhibited strong efficacy in preventing autotomy (self-mutilation) behaviors. This effect was linked to a substantial accumulation of MSCs in the neuroma and associated dorsal root ganglia and the establishment of an anti-inflammatory phenotype in these compartments. Centrally, this intervention reduced glial reactivity in the dorsal horn spinal cord, demonstrating diminished nociceptive activity. Accordingly, the exogenous systemic administration of MSCs phenocopied the behavioral effects of IMT504. Our findings underscore the mechanistic relevance of MSCs and the translational therapeutic potential of IMT504 to engage non-neuronal cells for the prevention of postamputation pain. PERSPECTIVE: The present study suggests that IMT504-dependent recruitment of endogenous MSCs within severely injured nerves may prevent post-amputation pain by modifying the inflammatory scenario at relevant sites in the pain pathway. Reinforcing data in rat and human tissues supports the potential therapeutic value of IMT504 in patients suffering postamputation pain.

Using Home-based, Remotely Supervised, Transcranial Direct Current Stimulation for Phantom Limb Pain.

Transcranial direct current stimulation (tDCS) is a noninvasive brain stimulation technique that uses low-amplitude direct currents to alter cortical excitability. Previous trials have established the safety and tolerability of tDCS, and its potential to mitigate symptoms. However, the effects are cumulative, making it more difficult to have adherence to the treatment since frequent visits to the clinic or outpatient center are required. Moreover, the time needed for transportation to the center and the related expenses limit the accessibility of the treatment for many participants. Following guidelines for remotely supervised transcranial direct current stimulation (RS-tDCS) implementation, we propose a protocol designed for remotely supervised and home-based participation that uses specific devices and materials modified for patient use, with real-time monitoring by researchers through an encrypted video conferencing platform. We have developed detailed instructional materials and structured training procedures to allow for self- or proxy-administration while supervised remotely in real time. This protocol has a specific design to have a series of checkpoints during training and execution of the visit. This protocol is currently in use in a large pragmatic study of RS-tDCS for phantom limb pain (PLP). In this article, we will discuss the operational challenges of conducting a home-based RS-tDCS session and show methods to enhance its efficacy with supervised sessions.

Transcranial magnetic stimulation in the treatment of phantom limb pain: a systematic review.

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.

ANTECEDENTES: A dor do membro fantasma (DMF) ocorre após amputações e pode persistir de forma crônica e debilitante. A estimulação magnética transcraniana repetitiva (EMTr) é um método de neuromodulação não invasivo capaz de influenciar a função cerebral e modular a excitabilidade cortical. Sua eficácia no tratamento da dor crônica é promissora. OBJETIVO: Avaliar as evidências sobre a eficácia e segurança do uso da EMTr no tratamento da DMF, observando os parâmetros de estimulação utilizados, efeitos colaterais e benefícios da terapia. MéTODOS: Trata-se de uma revisão sistemática de artigos científicos publicados na literatura nacional e internacional utilizando plataformas eletrônicas. RESULTADOS: Foram identificados 252 artigos. Duzentas e quarenta e seis publicações foram removidas por estarem duplicadas ou atenderem aos critérios de exclusão. Após a seleção, foram revisados seis estudos, sendo dois ensaios clínicos randomizados e quatro relatos de caso. Todos os estudos avaliados indicaram algum grau de benefício da EMTr no alívio dos sintomas dolorosos, mesmo que temporariamente. A percepção da dor foi menor ao final do tratamento quando comparada ao período anterior às sessões e permaneceu durante o acompanhamento do paciente. Não houve padronização dos parâmetros de estimulação utilizados. Não houve relatos de eventos adversos graves. Os efeitos da terapia a longo prazo não foram avaliados. CONCLUSãO: Existem alguns benefícios, mesmo que temporários, no uso da EMTr para alívio dos sintomas dolorosos na DMF. A estimulação de alta frequência em M1 demonstrou um efeito analgésico significativo. Dado o potencial demonstrado, mas limitado pela escassez de estudos de alta qualidade, são necessários mais estudos controlados para estabelecer e padronizar o uso clínico do método.

Is Phantom Limb Awareness Necessary for the Treatment of Phantom Limb Pain?

Phantom limb pain is attributed to abnormal sensorimotor cortical representations. Various feedback treatments have been applied to induce the reorganization of the sensorimotor cortical representations to reduce pain. We developed a training protocol using a brain-computer interface (BCI) to induce plastic changes in the sensorimotor cortical representation of phantom hand movements and demonstrated that BCI training effectively reduces phantom limb pain. By comparing the induced cortical representation and pain, the mechanisms worsening the pain have been attributed to the residual phantom hand representation. Based on our data obtained using neurofeedback training without explicit phantom hand movements and hand-like visual feedback, we suggest a direct relationship between cortical representation and pain. In this review, we summarize the results of our BCI training protocol and discuss the relationship between cortical representation and phantom limb pain. We propose a treatment for phantom limb pain based on real-time neuroimaging to induce appropriate cortical reorganization by monitoring cortical activities.

Modulations in high-density EEG during the suppression of phantom-limb pain with neurostimulation in upper limb amputees.

Phantom limb pain (PLP) is a distressing and persistent sensation that occurs after the amputation of a limb. While medication-based treatments have limitations and adverse effects, neurostimulation is a promising alternative approach whose mechanism of action needs research, including electroencephalographic (EEG) recordings for the assessment of cortical manifestation of PLP relieving effects. Here we collected and analyzed high-density EEG data in 3 patients (P01, P02, and P03). Peripheral nerve stimulation suppressed PLP in P01 but was ineffective in P02. In contrast, transcutaneous electrical nerve stimulation was effective in P02. In P03, spinal cord stimulation was used to suppress PLP. Changes in EEG oscillatory components were analyzed using spectral analysis and Petrosian fractal dimension. With these methods, changes in EEG spatio-spectral components were found in the theta, alpha, and beta bands in all patients, with these effects being specific to each individual. The changes in the EEG patterns were found for both the periods when PLP level was stationary and the periods when PLP was gradually changing after neurostimulation was turned on or off. Overall, our findings align with the proposed roles of brain rhythms in thalamocortical dysrhythmia or disruption of cortical excitation and inhibition which has been linked to neuropathic pain. The individual differences in the observed effects could be related to the specifics of each patient's treatment and the unique spectral characteristics in each of them. These findings pave the way to the closed-loop systems for PLP management where neurostimulation parameters are adjusted based on EEG-derived markers.

Use of virtual reality for the management of phantom limb pain: a systematic review.

PURPOSE: To summarize the research on the effectiveness of virtual reality (VR) therapy for the management of phantom limb pain (PLP). METHODS: Three databases (SCOPUS, Ovid Embase, and Ovid MEDLINE) were searched for studies investigating the use of VR therapy for the treatment of PLP. Original research articles fulfilling the following criteria were included: (i) patients 18 years and older; (ii) all etiologies of amputation; (iii) any level of amputation; (iv) use of immersive VR as a treatment modality for PLP; (v) self-reported objective measures of PLP before and after at least one VR session; (vi) written in English. RESULTS: A total of 15 studies were included for analysis. Fourteen studies reported decreases in objective pain scores following a single VR session or a VR intervention consisting of multiple sessions. Moreover, combining VR with tactile stimulation had a larger beneficial effect on PLP compared with VR alone. CONCLUSIONS: Based on the current literature, VR therapy has the potential to be an effective treatment modality for the management of PLP. However, the low quality of studies, heterogeneity in subject population and intervention type, and lack of data on long-term relief make it difficult to draw definitive conclusions.IMPLICATION FOR REHABILITATIONVirtual reality (VR) therapy has emerged as a new potential treatment option for phantom limb pain (PLP) that circumvents some limitations of mirror therapy.VR therapy was shown to decrease PLP following a single VR session as well as after an intervention consisting of multiple sessions.The addition of vibrotactile stimuli to VR therapy may lead to larger decreases in PLP scores compared with VR therapy alone.

Graded motor imagery and its phases for individuals with phantom limb pain following amputation: A scoping review.

OBJECTIVE: Three-phase graded motor imagery (limb laterality, explicit motor imagery, and mirror therapy) has been successful in chronic pain populations. However, when applied to phantom limb pain, an amputation-related pain, investigations often use mirror therapy alone. We aimed to explore evidence for graded motor imagery and its phases to treat phantom limb pain. DATA SOURCES: A scoping review was conducted following the JBI Manual of Synthesis and Preferred Reporting Items for Systematic Review and Meta-Analyses extension for Scoping Reviews. Thirteen databases, registers, and websites were searched. REVIEW METHODS: Published works on any date prior to the search (August 2023) were included that involved one or more graded motor imagery phases for participants ages 18+ with amputation and phantom limb pain. Extracted data included study characteristics, participant demographics, treatment characteristics, and outcomes. RESULTS: Sixty-one works were included representing 19 countries. Most were uncontrolled studies (31%). Many participants were male (75%) and had unilateral amputations (90%) of varying levels, causes, and duration. Most works examined one treatment phase (92%), most often mirror therapy (84%). Few works (3%) reported three-phase intervention. Dosing was inconsistent across studies. The most measured outcome was pain intensity (95%). CONCLUSION: Despite the success of three-phase graded motor imagery in other pain populations, phantom limb pain research focuses on mirror therapy, largely ignoring other phases. Participant demographics varied, making comparisons difficult. Future work should evaluate graded motor imagery effects and indicators of patient success. The represented countries indicate that graded motor imagery phases are implemented internationally, so future work could have a widespread impact.

The effectiveness of graded motor imagery and its components on phantom limb pain in amputated patients: A systematic review.

BACKGROUND: Phantom limb pain (PLP) can be defined as pain in a missing part of the limb. It is reported in 50%-80% of people with amputation. OBJECTIVES: To provide an overview of the effectiveness of graded motor imagery (GMI) and the techniques which form it on PLP in amputees. STUDY DESIGN: Systematic review. METHODS: Two authors independently selected relevant studies, screened the articles for methodological validity and risk of bias, and extracted the data. Inclusion criteria used were clinical studies, written in English or Spanish, using GMI, laterality recognition, motor imagery, mirror therapy, or a combination of some of them as an intervention in amputated patients, and one of the outcomes was PLP, and it was assessed using a validated scale. The databases used were PubMed, Scopus, Web of Science, CINAHL, and PEDro. RESULTS: Fifteen studies were included in the review. After the intervention, all the groups in which the GMI or one of the techniques that comprise it was used showed decrease in PLP. CONCLUSION: The 3 GMI techniques showed effectiveness in decreasing PLP in amputees, although it should be noted that the application of the GMI showed better results.

The Effect of Distant Reiki Applied to Individuals with Extremity Amputation on Pain Level and Holistic Well-Being: A Quasi-experimental Study.

BACKGROUND: Pain felt in an amputated limb is quite common. Phantom pain affects the lives of individuals in many ways and can negatively affect the holistic well-being of individuals. Distant Reiki can be used in the management of these problems. AIM: This study was conducted to examine the effect of distant Reiki applied to individuals with extremity amputation on pain level and holistic well-being. METHOD: This a quasi-experimental single group pre-test. Post-test design research was conducted between September 2022 and April 2023 and included 25 individuals with extremity amputation. Then, according to Classical Usui Reiki, distant Reiki application has been performed for 20 minutes every day for 10 days. Data were collected at the beginning of the study and at the end of the 10th day. The data were obtained using an Introductory Information Form, the Visual Analog Scale for Pain, and Holistic Well-Being Scale. RESULTS: The mean age of the participants was 51.32 ± 16.65 years. There was a significant difference between pre-test and post-test pain levels of the participants (p < .05) and HWBS subscale scores (p < .05). Accordingly, it was determined that after 20-minute distant Reiki sessions for 10 consecutive days, the pain levels of the individuals were significantly reduced and their holistic well-being improved. CONCLUSION: Distant Reiki has been found to be easy to administer, inexpensive, non-pharmacological, and appropriate for independent nursing practice to be effective in reducing phantom pain levels and increasing holistic well-being in people with limb amputation.

Evolving techniques for reducing phantom limb pain.

At least two million people in the United States of America live with lost limbs, and the number is expected to double by 2050, although the incidence of amputations is significantly greater in other parts of the world. Within days to weeks of the amputation, up to 90% of these individuals develop neuropathic pain, presenting as phantom limb pain (PLP). The pain level increases significantly within one year and remains chronic and severe for about 10%. Amputation-induced changes are considered to underlie the causation of PLP. Techniques applied to the central nervous system (CNS) and peripheral nervous system (PNS) are designed to reverse amputation-induced changes, thereby reducing/eliminating PLP. The primary treatment for PLP is the administration of pharmacological agents, some of which are considered but provide no more than short-term pain relief. Alternative techniques are also discussed, which provide only short-term pain relief. Changes induced by various cells and the factors they release are required to change neurons and their environment to reduce/eliminate PLP. It is concluded that novel techniques that utilize autologous platelet-rich plasma (PRP) may provide long-term PLP reduction/elimination.

Towards Implementation of a Home-Based Phantom Limb Pain Treatment Facilitated by Textile-Electrode System - A Case Study.

This case study reports the use of a new textile-electrode system for self-administered Phantom Motor Execution (PME) treatment at home in one patient with Phantom Limb Pain (PLP). In follow-up interviews, the patient reported reduced pain, increased mobility, and improved mental health, and aspects such as motivation, usability, support, and treatment outcome, could be recognized from an earlier study as crucial for successful implementation and adoption of the home-based long-term treatment. The findings are of interest to developers, providers, users, and researchers planning home-based clinical studies and/or scenarios based on technology-assisted treatment.

Mirror Therapy for the Management of Phantom Limb Pain: A Single- Center Experience.

BACKGROUND: Phantom limb pain (PLP) can have devastating consequences, affecting up to 90% of amputees. PLP is associated with analgesia dependence and impaired quality of life. Mirror therapy (MT) is a novel treatment that has been applied in other pain syndromes. We prospectively evaluated MT in the management of PLP. METHODS: A prospective study of patients recruited between 2008 and 2020 who underwent unilateral major limb amputation, with a healthy contralateral limb. Participants were invited to attend weekly MT sessions. Pain in the 7 days prior to each MT session was scored on a Visual Analog Scale (VAS: 0-10 mm) and the short form McGill pain questionnaire. RESULTS: Ninety eight patients (68 males and 30 females) aged 17-89 years were recruited over 12 years. Forty four percent of patients had amputations due to peripheral vascular disease. Over an average of 2.5 sessions, the final treatment score on the VAS scale was 2.6 (standard deviation ± 3.0) with a reduction of 4.5 points on VAS score. As a comparison using the short form McGill pain questionnaire scoring system, the average final treatment score was 3.2 (± 5.0) with 91% overall improvement. CONCLUSIONS: MT is a very powerful and effective intervention for PLP. It is an exciting addition to the armory of vascular surgeons in the management of this condition.

Peripheral nerve stimulation enables somatosensory feedback while suppressing phantom limb pain in transradial amputees.

To simultaneously treat phantom limb pain (PLP) and restore somatic sensations using peripheral nerve stimulation (PNS), two bilateral transradial amputees were implanted with stimulating electrodes in the proximity of the medial, ulnar and radial nerves. Application of PNS evoked tactile and proprioceptive sensations in the phantom hand. Both patients learned to determine the shape of invisible objects by scanning a computer tablet with a stylus while receiving feedback based on PNS or transcutaneous electrical nerve stimulation (TENS). Оne patient learned to use PNS as feedback from the prosthetic hand that grasped objects of different sizes. PNS abolished PLP completely in one patient and reduced it by 40-70% in the other. We suggest incorporating PNS and/or TENS in active tasks to reduce PLP and restore sensations in amputees.

Mindful SensoriMotor Therapy combined with brain modulation for the treatment of pain in individuals with disarticulation or nerve injuries: a single-arm clinical trial.

INTRODUCTION: Neuropathic pain is a complex and demanding medical condition that is often difficult to treat. Regardless of the cause, the impairment, lesion or damage to the nervous system can lead to neuropathic pain, such as phantom limb pain (PLP). No treatment has been found widely effective for PLP, but plasticity-guided therapies have shown the least severe side effects in comparison to pharmacological or surgical interventions. Phantom motor execution (PME) is a plasticity-guided intervention that has shown promising results in alleviating PLP. The potential mechanism underlying the effectiveness of PME can be explained by the Stochastic Entanglement hypothesis for neurogenesis of neuropathic pain resulting from sensorimotor impairment. We have built on this hypothesis to investigate the efficacy of enhancing PME interventions by using phantom motor imagery to facilitate execution and with the addition of sensory training. We refer to this new treatment concept as Mindful SensoriMotor Therapy (MiSMT). In this study, we further complement MiSMT with non-invasive brain modulation, specifically transcranial direct current stimulation (tDCS), for the treatment of neuropathic pain in patients with disarticulation or peripheral nerve injury. METHODS AND ANALYSIS: This single-arm clinical trial investigates the efficacy of MiSMT and tDCS as a treatment of neuropathic pain resulting from highly impaired extremity or peripheral nerve injury in eight participants. The study consists of 12 sessions of MiSMT with anodal tDCS in the motor cortex, pretreatment and post-treatment assessments, and follow-up sessions (up to 6 months). The primary outcome is the change in pain intensity as measured by the Pain Rating Index between the first and last treatment sessions. ETHICS AND DISSEMINATION: The study is performed under the approval of the governing ethical committee in Sweden (approval number 2020-07157) and in accordance with the Declaration of Helsinki. TRIAL REGISTRATION NUMBER: NCT04897425.

Detangling the Structural Neural Correlates Associated with Resting versus Dynamic Phantom Limb Pain Intensity Using a Voxel-based Morphometry Analysis.

The management of phantom limb pain (PLP) is still challenging due to a partial understanding of its neurophysiological mechanisms. Structural neuroimaging features are potential biomarkers. However, only a few studies assessed their correlations with clinical severity and treatment response. This study aims to explore the association between brain gray matter volume (GMV) with phantom limb manifestations severity and PLP improvement after neuromodulatory treatments (transcranial direct current stimulation and mirror therapy). Voxel-based morphometry analyses and functional decoding using a reverse inference term-based meta-analytic approach were used. We included 24 lower limb traumatic amputees with moderate to severe PLP. We found that alterations of cortical GMV were correlated with PLP severity but not with other clinical manifestations. Less PLP severity was associated with larger brain clusters GMV in the non-affected prefrontal, insula (non-affected mid-anterior region), and bilateral thalamus. However, only the insula cluster survived adjustments. Moreover, the reverse inference meta-analytic approach revealed that the found insula cluster is highly functionally connected to the contralateral insula and premotor cortices, and the decoded psychological processes related to this cluster were "rating," "sustained attention," "impulsivity, " and "suffering." Moreover, we found that responders to neuromodulatory treatment have higher GMV in somatosensory areas (total volume of S1 and S2) in the affected hemisphere at baseline, compared to non-responders, even after adjustments.

[Clinical updates on phantom limb pain : German version]. / Klinisches Update zu Phantomschmerz : Deutsche Fassung.

INTRODUCTION: Most patients with amputation (up to 80 %) suffer from phantom limb pain postsurgery. These are often multimorbid patients who also have multiple risk factors for the development of chronic pain from a pain medicine perspective. Surgical removal of the body part and sectioning of peripheral nerves result in a lack of afferent feedback, followed by neuroplastic changes in the sensorimotor cortex. The experience of severe pain, peripheral, spinal, and cortical sensitization mechanisms, and changes in the body scheme contribute to chronic phantom limb pain. Psychosocial factors may also affect the course and the severity of the pain. Modern amputation medicine is an interdisciplinary responsibility. METHODS: This review aims to provide an interdisciplinary overview of recent evidence-based and clinical knowledge. RESULTS: The scientific evidence for best practice is weak and contrasted by various clinical reports describing the polypragmatic use of drugs and interventional techniques. Approaches to restore the body scheme and integration of sensorimotor input are of importance. Modern techniques, including apps and virtual reality, offer an exciting supplement to already established approaches based on mirror therapy. Targeted prosthesis care helps to obtain or restore limb function and at the same time plays an important role reshaping the body scheme. DISCUSSION: Consequent prevention and treatment of severe postoperative pain and early integration of pharmacological and nonpharmacological interventions are required to reduce severe phantom limb pain. To obtain or restore body function, foresighted surgical planning and technique as well as an appropriate interdisciplinary management is needed.

Comparative Effects of Interventions on Phantom Limb Pain: A Network Meta-Analysis.

BACKGROUND: Phantom limb pain (PLP) is a common type of chronic pain that occurs after limb amputation. Many treatment approaches are available; however, the treatment of PLP is still a challenge. This study aimed to quantify and rank the efficacy of interventions for phantom limb pain. METHODS: A comprehensive literature search was performed using the databases of PubMed, MEDLINE, Embase, Web of Science, and Cochrane. A network meta-analysis was applied to formulate direct and indirect comparisons among interventions for PLP. RESULTS: Twenty-two studies comprising 662 patients and 13 different interventions were included in this study. The mirror therapy (MT) (-1.00; 95% confidence interval, -1.94 to -0.07) and MT + phantom exercise (PE) (-6.05; 95% confidence interval, -8.29 to -3.81) group presented significantly lower pain intensity compared with placebo. In SUCRA (surface under the cumulative ranking curve) analysis, the MT+PE and neuromodulation techniques groups had the highest SUCRA value (81.2). CONCLUSIONS: Our results suggest that MT is the most optimal treatment for PLP, and a combination of therapies would enhance the therapeutic effect.