Chronic Phantom Limb Pain Research Articles

Managing acute phantom limb pain with transcutaneous electrical nerve stimulation: a case report

IntroductionPhantom limb pain is characterized by painful sensations in the amputated limb. The clinical presentation of acute phantom limb pain may differ from that of patients with chronic phantom limb pain. The variation observed implies that acute phantom limb pain may be driven by peripheral mechanisms, indicating that therapies focused on the peripheral nervous system might be successful in reducing pain.Case presentationA 36-year-old African male with acute phantom limb pain in the left lower limb, was treated with transcutaneous electrical nerve stimulation.ConclusionThe assessment results of the presented case and the evidence on acute phantom limb pain mechanisms contribute to the current body of literature, indicating that acute phantom limb pain presents differently to chronic phantom limb pain. These findings emphasize the importance of testing treatments that target the peripheral mechanisms responsible for phantom limb pain in relevant individuals with acquired amputations.

Effect of perioperative sciatic nerve block on chronic pain in patients undergoing below-knee amputation: A randomised controlled trial

Many pain syndromes such as chronic phantom limb pain (PLP) and stump pain (SP), involving nociceptive and neuropathic pain, develop after amputation. Recent literature suggests that the use of regional blocks reduces repeated stimulation of transected nerve roots and thus prevents central sensitisation. This randomised, double-blind study was conducted to evaluate the effect of pre-emptive ultrasound-guided single-shot lateral sciatic nerve block on the occurrence of chronic pain at six months after traumatic below-knee amputation. Thirty patients undergoing traumatic lower limb amputation under general anaesthesia were randomised into two groups: Group B received sciatic nerve block pre-emptively using ultrasound with 20 ml of 0.75% ropivacaine, whereas group C received 20 ml of normal saline. Follow-up of patients was done till six months post-amputation. The primary objective was to assess the occurrence of chronic pain at six months. Pain at 15 days and one month after surgery, post-operative morphine consumption and post-operative nausea and vomiting (PONV) were the secondary outcomes assessed. The occurrence of PLP at six months was comparable in the two groups, group B (46.7%) and C (66.7%). None of the patients developed SP at six months. Median intensities of phantom pain were 1.0 (range, 1-2.0) versus 1.0 (range, 1-2.0) (P = 0.36), and median intensities of SP 2 (range, 2-3.0) versus 3 (range, 2-3.0) (P = 0.39) at 1 month. Pre-emptive sciatic nerve block did not decrease the occurrence or severity of chronic pain after traumatic below-knee amputation.

Clinical updates on phantom limb pain : German version

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. This review aims to provide an interdisciplinary overview of recent evidence-based and clinical knowledge. 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. 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.

Quality of Life among Lower Limb Amputees with Chronic Phantom Limb Pain or Stump Pain at a Tertiary Institution’s Pain Clinic

Background: Phantom pain and stump pain in amputees have negative physical and psychological impacts. These effects may influence the quality of life (QoL) of lower limb amputees. Objective: To explore QoL of lower limb amputees treated at Ramathibodi pain clinic. Materials and Methods: All lower limb amputees treated at Ramathibodi pain clinic in 2020 were invited to answer questionnaires, including demographic data, the Short Form-36 Health Survey (SF-36), and the Hospital Anxiety and Depression Scale (HADS). Participants were recruited to join a focus group discussion and individual interviews. Qualitative data were collected, and then analyzed using content analysis and inductive thematic analysis. Results: Twenty-two participants were recruited. Average SF-36 score was 49.17±10.07. Physical component summary was 23.36±15.27 and mental component summary was 68.02±16.45. HADS were 5.91±3.69 and 5.23±3.42 for anxiety and depression, respectively. Eight participants were selected for focus group discussion and individual interviews. Five themes emerged, including biopsychosocial effects of amputation, pain among amputees, concepts of encouragement in life, gaps between patients and multidisciplinary team staff, and effects of the COVID-19 pandemic. Conclusion: Lower limb amputees had low QoL. Amputation was found to restrict patients’ physical function, and good pain management was reported to be crucial to help amputees cope and accept their condition. Positive self-esteem and social support also played a significant role. Inadequate communication was found to be the main deficit requiring attention. Lockdown policies during the COVID-19 pandemic affected QoL but pain intensity was maintained with management via telemedicine. Keywords: Lower limb amputee; Quality of life; Phantom limb pain; Stump pain

The Prevalence and Characteristics of Phantom Limb Pain and Non-Painful Phantom Phenomena in a Nationwide Survey of 3,374 Unilateral Limb Amputees

The experience of phantom limb pain (PLP) is a common consequence of limb amputation, resulting in severe impairments of the affected person. Previous studies have shown that several factors such as age at or site of amputation are associated with the emergence and maintenance of PLP. In this cross-sectional study we assessed the presence of several phantom phenomena including PLP and other amputation-related information in a sample of 3,374 unilateral upper and lower limb amputees. Clinical and demographic variables (age at amputation, level of amputation) explained 10.6% of the variance in PLP and perceptual variables (intensity of phantom limb sensation [PLS], referred sensations, intensity of telescoping, residual limb pain [RLP] intensity) explained 16.9% of the variance. These variables were specific for PLP and not for RLP. These results suggest that distinct variables are associated with PLP (age at amputation, level of amputation, PLS intensity, referred sensations, intensity of telescoping, RLP intensity) and RLP (PLP intensity) and point at partly different mechanisms for the emergence and maintenance of PLP and RLP. PerspectiveClinical/demographic variables as well as perceptual variables are 2 major components related to PLP and explain ∼11% and ∼17% of the variance. These results could potentially help clinicians to understand which factors may contribute to chronic phantom limb pain.

Phantom limb pain after unilateral arm amputation is associated with decreased heat pain thresholds in the face

AbstractBackgroundThe mechanisms underlying chronic phantom limb pain (PLP) are complex and insufficiently understood. Altered sensory thresholds are often associated with chronic pain but quantitative sensory testing (QST) in PLP has so far been inconclusive due to large methodological variation between studies and small sample sizes.MethodsIn this study, we applied QST in 37 unilateral upper‐limb amputees (23 with and 14 without PLP) and 19 healthy controls. We assessed heat pain (HPT), pressure pain, warmth detection and two‐point discrimination thresholds at the residual limb, a homologous point and the thenar of the intact limb as well as both corners of the mouth.ResultsWe did not find significant differences in any of the thresholds between the groups. However, PLP intensity was negatively associated with HPT at all measured body sites except for the residual limb, indicating lower pain thresholds with higher PLP levels. Correlations between HPT and PLP were strongest in the contralateral face (r = −0.65, p < 0.001). Facial HPT were specifically associated with PLP, independent of residual limb pain (RLP) and various other covariates. HPT at the residual limb, however, were significantly associated with RLP, but not with PLP.ConclusionWe conclude that the association between PLP and, especially facial, HPT could be related to central mechanisms.SignificancePhantom limb pain (PLP) is still poorly understood. We show that PLP intensity is associated with lower heat pain thresholds, especially in the face. This finding could be related to central nervous changes in PLP.

Targeted Muscle Reinnervation for the Treatment of Neuroma.

Targeted muscle reinnervation (TMR) is the surgical rerouting of severed nerve endings to nearby expendable motor nerve branches. These nerve transfers provide a pathway for axonal growth, limiting the amputated nerve ends' disorganized attempt at regeneration that leads to neuroma formation. In the amputee population, TMR is successful in the treatment and prevention of chronic phantom limb pain and residual limb pain. In the nonamputee population, applications of TMR are ever expanding in the treatment of chronic neuroma pain owing to trauma, compression, or surgery. This article reviews the indications for TMR, preoperative evaluation, and various surgical techniques.

Clinical updates on phantom limb pain.

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. This review aims to provide an interdisciplinary overview of recent evidence-based and clinical knowledge. 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. 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.

BCI training to move a virtual hand reduces phantom limb pain: A randomized crossover trial.

ObjectiveTo determine whether training with a brain–computer interface (BCI) to control an image of a phantom hand, which moves based on cortical currents estimated from magnetoencephalographic signals, reduces phantom limb pain.MethodsTwelve patients with chronic phantom limb pain of the upper limb due to amputation or brachial plexus root avulsion participated in a randomized single-blinded crossover trial. Patients were trained to move the virtual hand image controlled by the BCI with a real decoder, which was constructed to classify intact hand movements from motor cortical currents, by moving their phantom hands for 3 days (“real training”). Pain was evaluated using a visual analogue scale (VAS) before and after training, and at follow-up for an additional 16 days. As a control, patients engaged in the training with the same hand image controlled by randomly changing values (“random training”). The 2 trainings were randomly assigned to the patients. This trial is registered at UMIN-CTR (UMIN000013608).ResultsVAS at day 4 was significantly reduced from the baseline after real training (mean [SD], 45.3 [24.2]–30.9 [20.6], 1/100 mm; p = 0.009 < 0.025), but not after random training (p = 0.047 > 0.025). Compared to VAS at day 1, VAS at days 4 and 8 was significantly reduced by 32% and 36%, respectively, after real training and was significantly lower than VAS after random training (p < 0.01).ConclusionThree-day training to move the hand images controlled by BCI significantly reduced pain for 1 week.Classification of evidenceThis study provides Class III evidence that BCI reduces phantom limb pain.

Peripheral input and phantom limb pain: A somatosensory event-related potential study.

Following amputation, nearly all amputees report nonpainful phantom phenomena and many of them suffer from chronic phantom limb pain (PLP) and residual limb pain (RLP). The aetiology of PLP remains elusive and there is an ongoing debate on the role of peripheral and central mechanisms. Few studies have examined the entire somatosensory pathway from the truncated nerves to the cortex in amputees with PLP compared to those without PLP. The relationship among afferent input, somatosensory responses and the change in PLP remains unclear. Transcutaneous electrical nerve stimulation was applied on the truncated median nerve, the skin of the residual limb and the contralateral homologous nerve in 22 traumatic upper-limb amputees (12 with and 10 without PLP). Using somatosensory event-related potentials, the ascending volley was monitored from the brachial plexus, the spinal cord, the brainstem and the thalamus to the primary somatosensory cortex. Peripheral input could evoke PLP in amputees with chronic PLP (7/12), but not in amputees without a history of PLP (0/10). The amplitudes of the somatosensory components were comparable between amputees with and without PLP. In addition, evoked potentials from the periphery through the spinal, subcortical and cortical segments were not significantly associated with PLP. Peripheral input can modulate PLP but seems insufficient to cause PLP. These findings suggest the multifactorial complexity of PLP and different mechanisms for PLP and RLP. Peripheral afferent input plays a role in PLP and has been assumed to be sufficient to generate PLP. In this study we found no significant differences in the electrical potentials generated by peripheral stimulation from the truncated nerve and the skin of the residual limb in amputees with and without PLP. Peripheral input could enhance existing PLP but could not cause it. These findings indicate the multifactorial complexity of PLP and an important role of central processes in PLP.

Protective and Risk Factors for Phantom Limb Pain and Residual Limb Pain Severity.

The 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. This 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. We 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). These 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.

Brain and spinal stimulation therapies for phantom limb pain: a systematic review

Although many treatments exist for phantom limb pain (PLP), the evidence supporting them is limited and there are no guidelines for PLP management. Brain and spinal cord neurostimulation therapies are targeted at patients with chronic PLP but have yet to be systematically reviewed. To determine which types of brain and spinal stimulation therapy appear to be the best for treating chronic PLP. Systematic reviews of effectiveness and epidemiology studies, and a survey of NHS practice. All patients with PLP. Invasive interventions - deep brain stimulation (DBS), motor cortex stimulation (MCS), spinal cord stimulation (SCS) and dorsal root ganglion (DRG) stimulation. Non-invasive interventions - repetitive transcranial magnetic stimulation (rTMS) and transcranial direct current stimulation (tDCS). Phantom limb pain and quality of life. Twelve databases (including MEDLINE and EMBASE) and clinical trial registries were searched in May 2017, with no date limits applied. Two reviewers screened titles and abstracts and full texts. Data extraction and quality assessments were undertaken by one reviewer and checked by another. A questionnaire was distributed to clinicians via established e-mail lists of two relevant clinical societies. All results were presented narratively with accompanying tables. Seven randomised controlled trials (RCTs), 30 non-comparative group studies, 18 case reports and 21 epidemiology studies were included. Results from a good-quality RCT suggested short-term benefits of rTMS in reducing PLP, but not in reducing anxiety or depression. Small randomised trials of tDCS suggested the possibility of modest, short-term reductions in PLP. No RCTs of invasive therapies were identified. Results from small, non-comparative group studies suggested that, although many patients benefited from short-term pain reduction, far fewer maintained their benefits. Most studies had important methodological or reporting limitations and few studies reported quality-of-life data. The evidence on prognostic factors for the development of chronic PLP from the longitudinal studies also had important limitations. The results from these studies suggested that pre-amputation pain and early PLP intensity are good predictors of chronic PLP. Results from the cross-sectional studies suggested that the proportion of patients with severe chronic PLP is between around 30% and 40% of the chronic PLP population, and that around one-quarter of chronic PLP patients find their PLP to be either moderately or severely limiting or bothersome. There were 37 responses to the questionnaire distributed to clinicians. SCS and DRG stimulation are frequently used in the NHS but the prevalence of use of DBS and MCS was low. Most responders considered SCS and DRG stimulation to be at least sometimes effective. Neurosurgeons had mixed views on DBS, but most considered MCS to rarely be effective. Most clinicians thought that a randomised trial design could be successfully used to study neurostimulation therapies. There was a lack of robust research studies. Currently available studies of the efficacy, effectiveness and safety of neurostimulation treatments do not provide robust, reliable results. Therefore, it is uncertain which treatments are best for chronic PLP. Randomised crossover trials, randomised N-of-1 trials and prospective registry trials are viable study designs for future research. The study is registered as PROSPERO CRD42017065387. The National Institute for Health Research Health Technology Assessment programme.

Relieving phantom limb pain with multimodal sensory-motor training

Objective. The causes for the disabling condition of phantom limb pain (PLP), affecting 85% of amputees, are so far unknown, with few effective treatments available. Sensory feedback based strategies to normalize the motor commands to control the phantom limb offer important targets for new effective treatments as the correlation between phantom limb motor control and sensory feedback from the motor intention has been identified as a possible mechanism for PLP development. Approach. Ten upper-limb amputees, suffering from chronic PLP, underwent 16 days of intensive training on phantom-limb movement control. Visual and tactile feedback, driven by muscular activity at the stump, was provided with the aim of reducing PLP intensity. Main results. A 32.1% reduction of PLP intensity was obtained at the follow-up (6 weeks after the end of the training, with an initial 21.6% reduction immediately at the end of the training) reaching clinical effectiveness for chronic pain reduction. Multimodal sensory-motor training on phantom-limb movements with visual and tactile feedback is a new method for PLP reduction. Significance. The study results revealed a substantial reduction in phantom limb pain intensity, obtained with a new training protocol focused on improving phantom limb motor output using visual and tactile feedback from the stump muscular activity executed to move the phantom limb.

Traditional and augmented reality mirror therapy for patients with chronic phantom limb pain (PACT study): results of a three-group, multicentre single-blind randomized controlled trial

Objective: To compare the effects of traditional mirror therapy (MT), a patient-centred teletreatment (PACT) and sensomotor exercises without a mirror on phantom limb pain (PLP). Design: Three-arm multicentre randomized controlled trial. Setting: Rehabilitation centres, hospital and private practices. Subjects: Adult patients with unilateral lower limb amputation and average PLP intensity of at least 3 on the 0–10 Numeric Rating Scale (NRS). Interventions: Subjects randomly received either four weeks of traditional MT followed by a teletreatment using augmented reality MT, traditional MT followed by self-delivered MT or sensomotor exercises of the intact limb without a mirror followed by self-delivered exercises. Main measures: Intensity, frequency and duration of PLP and patient-reported outcomes assessing limitations in daily life at baseline, 4 weeks, 10 weeks and 6 months. Results: In total, 75 patients received traditional MT (n = 25), teletreatment (n = 26) or sensomotor exercises (n = 24). Mean (SD) age was 61.1 (14.2) years and mean (SD) pain intensity was 5.7 (2.1) on the NRS. Effects of MT at four weeks on PLP were not significant. MT significantly reduced the duration of PLP at six months compared to the teletreatment (P = 0.050) and control group (P = 0.019). Subgroup analyses suggested significant effects on PLP in women, patients with telescoping and patients with a motor component in PLP. The teletreatment had no additional effects compared to self-delivered MT at 10 weeks and 6 months. Conclusion: Traditional MT over four weeks was not more effective than sensomotor exercises without a mirror in reducing PLP, although significant effects were suggested in some subgroups.

Development of a Multimodal Analgesia Protocol for Perioperative Acute Pain Management for Lower Limb Amputation.

Multimodal analgesia may include pharmacological components such as regional anesthesia, opioid and nonopioid systemic analgesics, nonsteroidal anti-inflammatories, and a variety of adjuvant agents. Multimodal analgesia has been reported for a variety of surgical procedures but not yet for lower limb amputation in vasculopathic patients. Perioperative pain management in these patients presents a particular challenge considering the multiple sources and pathways for acute and chronic pain that are involved, such as chronic ischemic limb pain, postoperative residual limb pain, coexisting musculoskeletal pain, phantom limb sensations, and chronic phantom limb pain. These pain mechanisms are explored and a proposed protocol for multimodal analgesia is outlined taking into account the common patient comorbidities found in this patient population.

Reaffirming the link between chronic phantom limb pain and maintained missing hand representation

Phantom limb pain (PLP) is commonly considered to be a result of maladaptive brain plasticity. This model proposes that PLP is mainly caused by reorganisation in the primary somatosensory cortex, presumably characterised by functional degradation of the missing hand representation and remapping of other body part representations. In the current study, we replicate our previous results by showing that chronic PLP correlates with maintained representation of the missing hand in the primary sensorimotor missing hand cortex. We asked unilateral upper-limb amputees to move their phantom hand, lips or other body parts and measured the associated neural responses using functional magnetic resonance imaging (fMRI). We confirm that amputees suffering from worse chronic PLP have stronger activity in the primary sensorimotor missing hand cortex while performing phantom hand movements. We find no evidence of lip representation remapping into the missing hand territory, as assessed by measuring activity in the primary sensorimotor missing hand cortex during lip movements. We further show that the correlation between chronic PLP and maintained representation of the missing hand cannot be explained by the experience of chronic non-painful phantom sensations or compensatory usage of the residual arm or an artificial arm (prosthesis). Together, our results reaffirm a likely relationship between persistent peripheral inputs pertaining to the missing hand representation and chronic PLP. Our findings emphasise a need to further study the role of peripheral inputs from the residual nerves to better understand the mechanisms underlying chronic PLP.

Strategies for prevention of lower limb post-amputation pain: A clinical narrative review.

Postamputation limb pain or phantom limb pain (PLP) develops due to the complex interplay of peripheral and central sensitization. The pain mechanisms are different during the initial phase following amputation as compared with the chronic PLP. The literature describes extensively about the management of established PLP, which may not be applicable as a preventive strategy for PLP. The novelty of the current narrative review is that it focuses on the preventive strategies of PLP. The institution of preoperative epidural catheter prior to amputation and its continuation in the immediate postoperative period reduced perioperative opioid consumption (Level II). Optimized preoperative epidural or intravenous patient–controlled analgesia starting 48 hours and continuing for 48 hours postoperatively decreased PLP at 6 months (Level II). Preventive role of epidural LA with ketamine (Level II) reduced persistent pain at 1 year and LA with calcitonin decreased PLP at 12 months (Level II). Peripheral nerve catheters have opioid sparing effect in the immediate postoperative period in postamputation patients (Level I), but evidence is low for the prevention of PLP (Level III). Gabapentin did not reduce the incidence or intensity of postamputation pain (Level II). The review in related context mentions evidence regarding therapeutic role of gabapentanoids, peripheral nerve catheters, and psychological therapy in established PLP. In future, randomized controlled trials with long-term follow-up of patients receiving epidural analgesia, perioperative peripheral nerve catheters, oral gabapentanoids, IV ketamine, or mechanism-based modality for prevention of PLP as primary outcome are required.

Origins of Phantom Limb Pain.

Phantom limb pain (PLP) is a chronic neuropathic pain occurring in 45-85% of patients who undergo major amputations of the upper and lower extremities. Chronic pain is physically and mentally debilitating, affecting an individual's potential for self-care and the performance of daily living activities essential for personal and economic independence. In addition, chronic 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 this condition. PLP manifest predominantly during two time frames post-amputation: during days to a month and again at around 1year. In most patients, the frequency and intensity of the chronic neuropathic pain diminish over time, but severe pain persists in about 5-10% of patients. The development and maintenance of neuropathic pain is attributed to extremity amputations causing changes in peripheral axon properties and neuronal circuitry in both the peripheral and central nervous systems: peripheral axons, dorsal root ganglia, the spinal cord, and the cortex. However, it is not clear how the changes in neuronal properties in these different locations affect neuropathic pain. Is pain initiated by one set of post-amputation changes while the pain is maintained by another set of changes? If one set of amputation-induced changes, such as those of peripheral axons, are reverted to normal, is the chronic pain reduced or eliminated, while reversing another set of neuronal changes and neuronal circuits to normal do not reduce or eliminate the pain? Or, must all the amputation-induced changes be reverted to normal for pain to be eliminated? While this review examines the mechanisms underlying the induction or maintenance of PLP, it is beyond its scope to examine the mechanisms that may permanently reduce or eliminate neuropathic pain. This paper is the first of two reviews in this journal and deals with the causes of chronic PLP development and maintenance, while the second review examines potential mechanisms that may be responsible for promoting the capacity to coping with PLP by reducing or eliminating it.

Real-time Classification of Non-Weight Bearing Lower-Limb Movements Using EMG to Facilitate Phantom Motor Execution: Engineering and Case Study Application on Phantom Limb Pain.

Phantom motor execution (PME), facilitated by myoelectric pattern recognition (MPR) and virtual reality (VR), is positioned to be a viable option to treat phantom limb pain (PLP). A recent clinical trial using PME on upper-limb amputees with chronic intractable PLP yielded promising results. However, further work in the area of signal acquisition is needed if such technology is to be used on subjects with lower-limb amputation. We propose two alternative electrode configurations to conventional, bipolar, targeted recordings for acquiring surface electromyography. We evaluated their performance in a real-time MPR task for non-weight-bearing, lower-limb movements. We found that monopolar recordings using a circumferential electrode of conductive fabric, performed similarly to classical bipolar recordings, but were easier to use in a clinical setting. In addition, we present the first case study of a lower-limb amputee with chronic, intractable PLP treated with PME. The patient’s Pain Rating Index dropped by 22 points (from 32 to 10, 68%) after 23 PME sessions. These results represent a methodological advancement and a positive proof-of-concept of PME in lower limbs. Further work remains to be conducted for a high-evidence level clinical validation of PME as a treatment of PLP in lower-limb amputees.

Memantine for the treatment of general neuropathic pain: a narrative review.

Neuropathic pain (NP) is difficult to treat and is associated with a decline in quality of life. NP aetiologies are numerous and a number of pathologies display neuropathic characteristics. Of the various N-methyl-d-aspartate antagonists that are alternatives to be recommended in first-line NP treatment, memantine has the safest side-effect profile and has long been approved in Alzheimer's disease. The review covers memantine studies in postherpetic neuralgia, diabetic pain, postoperative pain, complex regional pain syndrome, chronic phantom limb pain, opioid-refractory pain and fibromyalgia. Results were inconclusive because of studies with poor levels of evidence, paucity of trials and small samples. Two recent randomized trials, however, showed significant efficacy of memantine: one demonstrated prophylactic effects against postoperative neuralgia and pain-associated psychological impairment; in the other, memantine improved pain and cognition in fibromyalgia. Both studies found no side effects or adverse events. Given the high rate of therapeutic failure in chronic states, often because of adverse events, the excellent benefit/risk ratio of memantine in these pilot studies encourages further exploration of this drug in NP prevention and in fibromyalgia in larger-scale studies.