Induced sensorimotor brain plasticity controls pain in phantom limb patients.
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ABSTRACT:
SUBMITTER: Yanagisawa T
PROVIDER: S-EPMC5095287 | biostudies-literature | 2016 Oct
REPOSITORIES: biostudies-literature
Publications
Induced sensorimotor brain plasticity controls pain in phantom limb patients.
Yanagisawa Takufumi T Fukuma Ryohei R Seymour Ben B Hosomi Koichi K Kishima Haruhiko H Shimizu Takeshi T Yokoi Hiroshi H Hirata Masayuki M Yoshimine Toshiki T Kamitani Yukiyasu Y Saitoh Youichi Y
Nature communications 20161027
The cause of pain in a phantom limb after partial or complete deafferentation is an important problem. A popular but increasingly controversial theory is that it results from maladaptive reorganization of the sensorimotor cortex, suggesting that experimental induction of further reorganization should affect the pain, especially if it results in functional restoration. Here we use a brain-machine interface (BMI) based on real-time magnetoencephalography signals to reconstruct affected hand moveme ...[more]
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Project description:ObjectivePhantom limb pain (PLP) is notoriously difficult to treat, partly due to an incomplete understanding of PLP-related disease mechanisms. Noninvasive brain stimulation (NIBS) is used to modulate plasticity in various neuropathological diseases, including chronic pain. Although NIBS can alleviate neuropathic pain (including PLP), both disease and treatment mechanisms remain tenuous. Insight into the mechanisms underlying both PLP and NIBS-induced PLP relief is needed for future implementation of such treatment and generalization to related conditions.MethodsWe used a within-participants, double-blind, and sham-controlled design to alleviate PLP via task-concurrent NIBS over the primary sensorimotor missing hand cortex (S1/M1). To specifically influence missing hand signal processing, amputees performed phantom hand movements during anodal transcranial direct current stimulation. Brain activity was monitored using neuroimaging during and after NIBS. PLP ratings were obtained throughout the week after stimulation.ResultsA single session of intervention NIBS significantly relieved PLP, with effects lasting at least 1 week. PLP relief associated with reduced activity in the S1/M1 missing hand cortex after stimulation. Critically, PLP relief and reduced S1/M1 activity correlated with preceding activity changes during stimulation in the mid- and posterior insula and secondary somatosensory cortex (S2).InterpretationThe observed correlation between PLP relief and decreased S1/M1 activity confirms our previous findings linking PLP with increased S1/M1 activity. Our results further highlight the driving role of the mid- and posterior insula, as well as S2, in modulating PLP. Lastly, our novel PLP intervention using task-concurrent NIBS opens new avenues for developing treatment for PLP and related pain conditions. ANN NEUROL 2019;85:59-73.
| S-EPMC6492189 | biostudies-literature
Project description:Following arm amputation the region that represented the missing hand in primary somatosensory cortex (S1) becomes deprived of its primary input, resulting in changed boundaries of the S1 body map. This remapping process has been termed 'reorganisation' and has been attributed to multiple mechanisms, including increased expression of previously masked inputs. In a maladaptive plasticity model, such reorganisation has been associated with phantom limb pain (PLP). Brain activity associated with phantom hand movements is also correlated with PLP, suggesting that preserved limb functional representation may serve as a complementary process. Here we review some of the most recent evidence for the potential drivers and consequences of brain (re)organisation following amputation, based on human neuroimaging. We emphasise other perceptual and behavioural factors consequential to arm amputation, such as non-painful phantom sensations, perceived limb ownership, intact hand compensatory behaviour or prosthesis use, which have also been related to both cortical changes and PLP. We also discuss new findings based on interventions designed to alter the brain representation of the phantom limb, including augmented/virtual reality applications and brain computer interfaces. These studies point to a close interaction of sensory changes and alterations in brain regions involved in body representation, pain processing and motor control. Finally, we review recent evidence based on methodological advances such as high field neuroimaging and multivariate techniques that provide new opportunities to interrogate somatosensory representations in the missing hand cortical territory. Collectively, this research highlights the need to consider potential contributions of additional brain mechanisms, beyond S1 remapping, and the dynamic interplay of contextual factors with brain changes for understanding and alleviating PLP.
| S-EPMC7422832 | biostudies-literature
Project description:Following amputation, individuals ubiquitously report experiencing lingering sensations of their missing limb. While phantom sensations can be innocuous, they are often manifested as painful. Phantom limb pain (PLP) is notorious for being difficult to monitor and treat. A major challenge in PLP management is the difficulty in assessing PLP symptoms, given the physical absence of the affected body part. Here, we offer a means of quantifying chronic PLP by harnessing the known ability of amputees to voluntarily move their phantom limbs. Upper-limb amputees suffering from chronic PLP performed a simple finger-tapping task with their phantom hand. We confirm that amputees suffering from worse chronic PLP had worse motor control over their phantom hand. We further demonstrate that task performance was consistent over weeks and did not relate to transient PLP or non-painful phantom sensations. Finally, we explore the neural basis of these behavioural correlates of PLP. Using neuroimaging, we reveal that slower phantom hand movements were coupled with stronger activity in the primary sensorimotor phantom hand cortex, previously shown to associate with chronic PLP. By demonstrating a specific link between phantom hand motor control and chronic PLP, our findings open up new avenues for PLP management and improvement of existing PLP treatments.
| S-EPMC5637164 | biostudies-literature
Project description:The aim of this study was to investigate whether a special prosthetic training in phantom limb pain patients aimed at increasing the functional use of the prosthesis leads to neural morphological plasticity of brain structures and a reduction in phantom limb pain. For chronic pain disorders, it was shown that morphological alterations due to pain might become at least partially reversed by pain therapies. Phantom limb pain is a chronic pain disorder that is frequently followed by neural plasticity of anatomical brain structures. In our study, 10 patients with amputation of the upper limb participated in a two-week training with a myoelectric prosthesis with somatosensory feedback. Grip strength was fed back with electrocutaneous stimulus patterns applied to the stump. Phantom limb pain was assessed before and after the two-week training. Similarly, two T1 weighted MRI scans were conducted for longitudinal thickness analyses of cortical brain structures. As result of this treatment, patients experienced a reduction in phantom limb pain and a gain in prosthesis functionality. Furthermore, we found a change of cortical thickness in small brain areas in the visual stream and the post-central gyrus ipsilateral to the amputation indicating morphological alterations in brain areas involved in vision and pain processing.
| S-EPMC5476738 | biostudies-literature
Project description:Currently, there is neither a standardized mode for the documentation of phantom sensations and phantom limb pain, nor for their visualization as perceived by patients. We have therefore created a tool that allows for both, as well as for the quantification of the patient's visible and invisible body image. A first version provides the principal functions: (1) Adapting a 3D avatar for self-identification of the patient; (2) modeling the shape of the phantom limb; (3) adjusting the position of the phantom limb; (4) drawing pain and cramps directly onto the avatar; and (5) quantifying their respective intensities. Our tool (C.A.L.A.) was evaluated with 33 occupational therapists, physiotherapists, and other medical staff. Participants were presented with two cases in which the appearance and the position of the phantom had to be modeled and pain and cramps had to be drawn. The usability of the software was evaluated using the System Usability Scale and its functional range was evaluated using a self-developed questionnaire and semi-structured interview. In addition, our tool was evaluated on 22 patients with limb amputations. For each patient, body image as well as phantom sensation and pain were modeled to evaluate the software's functional scope. The accuracy of the created body image was evaluated using a self-developed questionnaire and semi-structured interview. Additionally, pain sensation was assessed using the SF-McGill Pain Questionnaire. The System Usability Scale reached a level of 81%, indicating high usability. Observing the participants, though, identified several operational difficulties. While the provided functions were considered useful by most participants, the semi-structured interviews revealed the need for an improved pain documentation component. In conclusion, our tool allows for an accurate visualization of phantom limbs and phantom limb sensations. It can be used as both a descriptive and quantitative documentation tool for analyzing and monitoring phantom limbs. Thus, it can help to bridge the gap between the therapist's conception and the patient's perception. Based on the collected requirements, an improved version with extended functionality will be developed.
| S-EPMC9397903 | biostudies-literature
Project description:IntroductionThe exact mechanisms underlying the development and maintenance of phantom limb pain (PLP) are still unclear. This study aimed to identify the factors affecting pain intensity in patients with chronic, lower limb, traumatic PLP.MethodsThis is a cross-sectional analysis of patients with PLP. We assessed amputation-related and pain-related clinical and demographic variables. We used univariate and multivariate models to evaluate the associated factors modulating PLP and residual limb pain (RLP) intensity.ResultsWe included 71 unilateral traumatic lower limb amputees. Results showed that (1) amputation-related perceptions were experienced by a large majority of the patients with chronic PLP (sensations: 90.1%, n = 64; residual pain: 81.7%, n = 58); (2) PLP intensity has 2 significant protective factors (phantom limb movement and having effective treatment for PLP previously) and 2 significant risk factors (phantom limb sensation intensity and age); and (3) on the other hand, for RLP, risk factors are different: presence of pain before amputation and level of amputation (in addition to the same protective factors).ConclusionThese results suggest different neurobiological mechanisms to explain PLP and RLP intensity. While PLP risk factors seem to be related to maladaptive plasticity, since phantom sensation and older age are associated with more pain, RLP risk factors seem to have components leading to neuropathic pain, such as the amount of neural lesion and previous history of chronic pain. Interestingly, the phantom movement appears to be protective for both phenomena.
| S-EPMC7363546 | biostudies-literature
Project description:BackgroundMirror therapy has been demonstrated to reduce phantom limb pain (PLP) experienced by unilateral limb amputees. Research suggests that the visual feedback of observing a limb moving in the mirror is critical for therapeutic efficacy.ObjectiveSince mirror therapy is not an option for bilateral lower limb amputees, the purpose of this study was to determine if direct observation of another person's limbs could be used to relieve PLP.MethodsWe randomly assigned 20 bilateral lower limb amputees with PLP to visual observation (n = 11) or mental visualization (n = 9) treatment. Treatment consisted of seven discrete movements which were mimicked by the amputee's phantom limbs moving while visually observing the experimenter's limbs moving, or closing the eyes while visualizing and attempting the movements with their phantom limbs, respectively. Participants performed movements for 20 min daily for 1 month. Response to therapy was measured using a 100-mm visual analog scale (VAS) and the McGill Short-Form Pain Questionnaire (SF-MPQ).ResultsDirect visual observation significantly reduced PLP in both legs (P < 0.05). Amputees assigned to the mental visualization condition did not show a significant reduction in PLP.InterpretationDirect visual observation therapy is an inexpensive and effective treatment for PLP that is accessible to bilateral lower limb amputees.
| S-EPMC4241790 | biostudies-literature
Project description:The neural mechanism of phantom limb pain (PLP) is related to the intense brain reorganization process implicating plasticity after deafferentation mostly in sensorimotor system. There is a limited understanding of the association between the sensorimotor system and PLP. We used a novel task-based functional magnetic resonance imaging (fMRI) approach to (1) assess neural activation within a-priori selected regions-of-interested (motor cortex [M1], somatosensory cortex [S1], and visual cortex [V1]), (2) quantify the cortical representation shift in the affected M1, and (3) correlate these changes with baseline clinical characteristics. In a sample of 18 participants, we found a significantly increased activity in M1 and S1 as well as a shift in motor cortex representation that was not related to PLP intensity. In an exploratory analyses (not corrected for multiple comparisons), they were directly correlated with time since amputation; and there was an association between increased activity in M1 with a lack of itching sensation and V1 activation was negatively correlated with PLP. Longer periods of amputation lead to compensatory changes in sensory-motor areas; and itching seems to be a protective marker for less signal changes. We confirmed that PLP intensity is not associated with signal changes in M1 and S1 but in V1.
| S-EPMC9394643 | biostudies-literature
Project description:IntroductionPhantom limb pain (PLP) is a complex condition resulting in pain in the missing limb affecting 60-80% amputees. Increasing number of patients are undergoing amputations. Approximately 1 per every 1000 people in the United Kingdom is an amputee. Incidence of PLP can be as high as 80% following amputation. PLP can be severe and difficult to treat. A range of pharmacological interventions exist yet little is known about them in respect to PLP. This article will address the effectiveness of both single pharmacological, therapy as well as drug combination therapy.MethodsWe reviewed all literature looking at the evidence for the efficacy of both single and combined pharmacological therapy in the management of phantom limb pain. Not all commonly prescribed analgesic agents have been studied in the use of PLP and in these cases, the evidence of their efficacy in neuropathic pain was reviewed.ConclusionIt is difficult to draw definitive conclusions on the pharmacological management of PLP based on current available evidence. Most trials involved small cohorts and were not specific to the PLP. The trials which looked specifically at the PLP population gave conflicting results. Only the N-methyl-d-aspartate (NMDA) receptor antagonist class demonstrated consistent positive results. Most notably ketamine did produce a reduction in pressure pain thresholds and pain windup associated with PLP, although the numbers in these studies remain small. This benefit was not demonstrated across all NMDA receptor antagonists. Combination therapy has demonstrated effectiveness in previous studies for neuropathic pain but this has never been tested specifically against a PLP cohort. Therefore, combination treatment of agents with proven efficacy in PLP such as opioid and gabapentin deserves a closer examination in a controlled study against a placebo as well as single drug therapy.
| S-EPMC6194972 | biostudies-literature
Project description:Post-amputation phantom limb pain (PLP) is highly prevalent and very difficult to treat. The high-prevalence, high-pain intensity levels, and decreased quality of life associated with PLP compel us to explore novel avenues to prevent, manage, and reverse this chronic pain condition. This narrative review focuses on recent advances in the treatment of PLP and reviews evidence of mechanism-based treatments from randomized controlled trials published over the past 5 years. We review recent evidence for the efficacy of targeted muscle reinnervation, repetitive transcranial magnetic stimulation, imaginal phantom limb exercises, mirror therapy, virtual and augmented reality, and eye movement desensitization and reprocessing therapy. The results indicate that not one of the above treatments is consistently better than a control condition. The challenge remains that there is little level 1 evidence of efficacy for PLP treatments and most treatment trials are underpowered (small sample sizes). The lack of efficacy likely speaks to the multiple mechanisms that contribute to PLP both between and within individuals who have sustained an amputation. Research approaches are called for to classify patients according to shared factors and evaluate treatment efficacy within classes. Subgroup analyses examining sex effects are recommended given the clear differences between males and females in pain mechanisms and outcomes. Use of novel data analytical approaches such as growth mixture modeling for multivariate latent classes may help to identify sub-clusters of patients with common outcome trajectories over time.
| S-EPMC6652103 | biostudies-literature