Research Library

Surgical procedures, including nerve reconstruction and end-organ muscle reinnervation, have become more prominent in the prosthetic field over the past decade. Primarily developed to increase the functionality of prosthetic limbs, these surgical procedures have also been found to reduce postamputation neuropathic pain. Today, some of these procedures are performed more frequently for the management and prevention of postamputation pain than for prosthetic fitting, indicating a significant need for effective solutions to postamputation pain. One notable emerging procedure in this context is the Regenerative Peripheral Nerve Interface (RPNI). RPNI surgery involves an operative approach that entails splitting the nerve end longitudinally into its main fascicles and implanting these fascicles within free denervated and devascularized muscle grafts. The RPNI procedure takes a proactive stance in addressing freshly cut nerve endings, facilitating painful neuroma prevention and treatment by enabling the nerve to regenerate and innervate an end organ, i.e., the free muscle graft. Retrospective studies have shown RPNI’s effectiveness in alleviating postamputation pain and preventing the formation of painful neuromas. The increasing frequency of utilization of this approach has also given rise to variations in the technique. This article aims to provide a step-by-step description of the RPNI procedure, which will serve as the standardized procedure employed in an international, randomized controlled trial (ClinicalTrials.gov, NCT05009394). In this trial, RPNI is compared to two other surgical procedures for postamputation pain management, specifically, Targeted Muscle Reinnervation (TMR) and neuroma excision coupled with intra-muscular transposition and burying.

Over the past decade, the field of prosthetics has witnessed significant progress, particularly in the development of surgical techniques to enhance the functionality of prosthetic limbs. Notably, novel surgical interventions have had an additional positive outcome, as individuals with amputations have reported neuropathic pain relief after undergoing such procedures. Subsequently, surgical techniques have gained increased prominence in the treatment of postamputation pain, including one such surgical advancement – targeted muscle reinnervation (TMR). TMR involves a surgical approach that reroutes severed nerves as a type of nerve transfer to “target” motor nerves and their accompanying motor end plates within nearby muscles. This technique originally aimed to create new myoelectric sites for amplified electromyography (EMG) signals to enhance prosthetic intuitive control. Subsequent work showed that TMR also could prevent the formation of painful neuromas as well as reduce postamputation neuropathic pain (e.g., Residual and Phantom Limb Pain). Indeed, multiple studies have demonstrated TMR’s effectiveness in mitigating postamputation pain as well as improving prosthetic functional outcomes. However, technical variations in the procedure have been identified as it is adopted by clinics worldwide. The purpose of this article is to provide a detailed step-by-step description of the TMR procedure, serving as the foundation for an international, randomized controlled trial (ClinicalTrials.gov, NCT05009394), including nine clinics in seven countries. In this trial, TMR and two other surgical techniques for managing postamputation pain will be evaluated.

Background: Painful conditions such as residual limb pain (RLP) and phantom limb pain (PLP) can manifest after amputation. The mechanisms underlying such postamputation pains are diverse and should be addressed accordingly. Different surgical treatment methods have shown potential for alleviating RLP due to neuroma formation — commonly known as neuroma pain — and to a lesser degree PLP. Two reconstructive surgical interventions, namely targeted muscle reinnervation (TMR) and regenerative peripheral nerve interface (RPNI), are gaining popularity in postamputation pain treatment with promising results. However, these two methods have not been directly compared in a randomised controlled trial (RCT). Here, we present a study protocol for an international, double-blind, RCT to assess the effectiveness of TMR, RPNI, and a non-reconstructive procedure called neuroma transposition (active control) in alleviating RLP, neuroma pain, and PLP. Methods: One hundred ten upper and lower limb amputees suffering from RLP will be recruited and assigned randomly to one of the surgical interventions (TMR, RPNI, or neuroma transposition) in an equal allocation ratio. Complete evaluations will be performed during a baseline period prior to the surgical intervention, and follow-ups will be conducted in short term (1, 3, 6, and 12 months post-surgery) and in long term (2 and 4 years post-surgery). After the 12-month follow-up, the study will be unblinded for the evaluator and the participants. If the participant is unsatisfied with the outcome of the treatment at that time, further treatment including one of the other procedures will be discussed in consultation with the clinical investigator at that site. Discussion: A double-blind RCT is necessary for the establishment of evidence-based procedures, hence the motivation for this work. In addition, studies on pain are challenging due to the subjectivity of the experience and the lack of objective evaluation methods. Here, we mitigate this problem by including different pain evaluation methods known to have clinical relevance. We plan to analyse the primary variable, mean change in NRS (0–10) between baseline and the 12-month follow-up, using the intention-to-treat (ITT) approach to minimise bias and keep the advantage of randomisation. The secondary outcomes will be analysed on both ITT and per-protocol (PP). An adherence protocol (PP population) analysis will be used for estimating a more realistic effect of treatment. Trial registration: ClincialTrials.gov NCT05009394.

We developed a medical sensory training device, the device can give a wide variaty of sensations to the skin. During validation tests, we showed that peoples’ capability to distinguish different sensations improved. This may allow us to reduce the pain and restore function in people with neurological diseases.

This article describes the protocol for Mindful SensoriMotor Therapy in combination with Brain Modulation. This therapy will be used for the treatment of pain in individuals with disarticulations or nerve injuries.

A mathematical model of possible mechanisms contributing to phantom limb pain. By modelling the activity of neurons in the spinal cord we can recreate several characteristics that are typical for pain. We then explore how the system behaves after a severe nerve injury, such as an amputation, and how this could contribute to phantom limb pain.

Phantom limb pain (PLP) is a complex medical condition that is often difficult to treat, and thus can become detrimental to patients’ quality of life. No standardized clinical treatments exist and there is no conclusive understanding of the underlying mechanisms causing it. Noninvasive brain stimulation (NIBS) has been used to find correlations between changes in brain activity and various brain conditions, including neurological disease, mental illnesses, and brain disorders. Studies have also shown that NIBS can be effective in alleviating pain. Here, we examined the literature on a particular type of NIBS, known as transcranial direct current stimulation (tDCS), and its application to the treatment of PLP.We first discuss the current hypotheses on theworkingmechanism of tDCS and then we examine published evidence of its efficacy to treat PLP. We conclude this article by discussing how tDCS alone, and in combination with brain imaging techniques such as electroencephalography (EEG) and magnetic resonance imagining, could be applied to further investigate the mechanisms underlyingPLP.

Electrodes used for measuring electric signals from the body are commonly made of metal making them expensive, stiff, non-efficient potentially toxic. We made electrodes made of graphene induced with a laser allows for an economical, soft, and organic electrode. We tested the graphene electrode on the bench and in humans and found that they were more stable in bench testing and rivals metal electrodes in human testing. Graphene electrodes show potential to replace metal electrodes leading to better and cheaper electrodes.

To promote transparency and proper adherence to the scientific method, we published a protocol for the statistics we planned to conduct for our international clincial trial investigating purposeful control over the phantom limb as a treatment for phantom limb pain. The primary outcome of the study is to examine whether 15 sessions of out treatment can induce greater phantom limb pain relief, compared to a placebo treatment. The statistical analysis plan was written and published prior to reviewing the completed dataset to reduce bias when reporting the overall study results. The degree of phantom limb pain relief, in addition to other study outcomes to be examined, will provide insight into the mechanism behind phantom limb pain and its treatments, which serves to guide future developments of phantom limb pain treatments.

Phantom Limb Pain (PLP) is a chronic condition frequent among individuals with acquired amputation. PLP has been often investigated with the use of functional MRI focusing on the changes that take place in the sensorimotor cortex after amputation. In the present study, we investigated whether a different type of data, namely electroencephalographic (EEG) recordings, can be used to study the condition. We acquired resting state EEG data from people with and without PLP and then used machine learning for a binary classification task that differentiates the two. Common Spatial Pattern (CSP) decomposition was used as the feature extraction method and two validation schemes were followed for the classification task. Six classifiers (LDA, Log, QDA, LinearSVC, SVC and RF) were optimized through grid search and their performance compared. Two validation approaches, namely all-subjects validation and leave-one-out cross-validation (LOOCV), resulted in high classification accuracy. Most notably, the 93.7% accuracy achieved with SVC in LOOCV holds promise for good diagnostic capabilities using EEG biomarkers. In conclusion, our findings indicate that EEG data is a promising target for future research aiming at elucidating the neural mechanisms underlying PLP and its diagnosis.