Explore the vast range of titles available.

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 ClinicalTrials.gov NCT05009394.

ObjectivesRandomised controlled trial of the effect of a perineural infusion of levobupivacaine on moderate/severe phantom limb pain 6 months after major lower limb amputation.SettingSingle-centre, UK university hospital.ParticipantsNinety patients undergoing above-knee and below-knee amputation for chronic limb threatening ischaemia under general anaesthesia. Exclusion criteria were patients having surgery under neuraxial anaesthesia; inability to operate a patient-controlled analgesia device or complete a Visual Analogue Scale; amputation for trauma or malignancy; or contraindication to levobupivacaine.InterventionsEither levobupivacaine 0.125% or saline 0.9% (10 mL bolus, infusion of 8 mL/hour for 96 hours) via a sciatic or posterior tibial nerve sheath catheter placed under direct vision during surgery.Primary and secondary outcome measuresThe primary outcome measure was the presence of phantom limb pain, residual limb pain and phantom limb sensations up to 6 months after amputation. Secondary outcome measures included early postoperative pain and morphine requirements after surgery.ResultsData from 81 participants were analysed; 6-month follow-up data were available for 62 patients. Pain and morphine requirements varied widely before and after amputation in both groups. The incidences of moderate/severe phantom limb pain, residual limb pain and phantom limb sensations were low from 6 weeks with no significant differences between groups in phantom limb pain at rest (OR 0.56, 95% CI 0.14 to 2.14, p=0.394) or movement (OR 0.58, 95% CI 0.15 to 2.21, p=0.425) at 6 months. Early postoperative pain scores were low in both groups with no between-group differences in residual limb pain or phantom limb sensations (rest or movement) at any time point. High postoperative morphine consumption was associated with worsening phantom limb pain both at rest (−17.51, 95% CI −24.29 to −10.74; p<0.001) and on movement (−18.54, 95% CI −25.58 to −11.49; p<0.001). The incidence of adverse effects related to the study was low in both groups: postoperative nausea, vomiting and sedation scores were similar, and there were no features of local anaesthetic toxicity.ConclusionsLong-term phantom limb pain, residual limb pain and phantom limb sensations were not reduced significantly by perineural infusion of levobupivacaine, although the study was underpowered to show significant differences in the primary outcome. The incidence of phantom limb pain was lower than previously reported, possibly attributable to frequent assessment and early intervention to identify and treat postoperative pain when it occurred. There were large variations in postoperative pain scores, high requirements for analgesics before and after surgery and some problems maintaining recruitment and long -term follow-up. Knowledge of these potential problems should inform future research in this group of patients. Further work should investigate the association between perioperative morphine requirements and late phantom limb pain.Trial registration numbersEudraCT 2007-000619-27; ISRCTN68691928.

ObjectivesTo determine the feasibility of undertaking a randomised controlled effectiveness trial evaluating the use of a perineural catheter (PNC) after major lower limb amputation with postoperative pain as the primary outcome.DesignRandomised controlled feasibility trial.SettingTwo vascular Centres in South Wales, UK.Participants50 patients scheduled for major lower limb amputation (below or above knee) for complications of peripheral vascular disease.InterventionsThe treatment arm received a PNC placed adjacent to the sciatic or tibial nerve at the time of surgery, with continuous infusion of levobupivacaine hydrochloride 0.125% for up to 5 days. The control arm received neither local anaesthetic nor PNC. Both arms received usual perioperative anaesthesia and postoperative analgesia.Primary and secondary outcome measuresThe primary outcomes were the proportion of eligible patients who were randomised and the proportion of recruited patients who provided primary effectiveness outcome data. Secondary outcomes were: the proportion of recruited patients reaching 2 and 6 month follow-up and supplying pain data; identification of key cost drivers; development of an economic analysis framework for a future effectiveness trial; identification of barriers to recruitment and site set-up; and identification of the best way to measure postoperative pain.ResultsSeventy-six of 103 screened patients were deemed eligible over a 10 month period. Fifty (64.5%) of these patients were randomised, with one excluded in the perioperative period. Forty-five (91.3%) of 49 recruited patients provided enough pain scores on a 4-point verbal rating scale to allow primary effectiveness outcome evaluation. Attrition rates were high; 18 patients supplied data at 6 month follow-up. Costs were dominated by length of hospital stay. Patients and healthcare professionals reported that trial processes were acceptable.ConclusionsRecruitment of patients into a trial comparing PNC use to usual care after major lower limb amputation with postoperative pain measured on a 4-point verbal rating scale is feasible. Evaluation of longer-term symptoms is difficult.Trial registration numberISRCTN: 85 710 690. EudraCT: 2016-003544-37.

Background Turning gait is an integral part of daily ambulation and likely poses a greater challenge for patients with transtibial amputation compared with walking a straight pathway. A torsion adapter is a prosthetic component that can increase transverse plane compliance of the prosthesis and decrease the torque applied to the residual limb, but whether this will improve patients’ mobility, pain, and fatigue remains unknown. Questions/purposes Does prescription of a torsion adapter translate to improvements in (1) functional mobility and (2) self-perceived pain and fatigue in moderately active patients with lower limb amputation? Methods Ten unilateral transtibial amputees wore a torsion or rigid adapter in random order. Functional mobility was assessed through a field measurement using an activity monitor and through a laboratory measurement using a 6-minute walk test that included turns. The residual limb pain grade assessed self-perceived pain and the Multidimensional Fatigue Inventory assessed fatigue. Results We found relatively small functional differences for amputees wearing a torsion adapter versus a rigid adapter. Amputees wearing a torsion adapter tended to take more low- and medium-intensity steps per day (331 ± 365 and 437 ± 511 difference in steps; effect size = 0.44 and 0.17; confidence interval [CI], 70–592 and 71–802; p = 0.019 and 0.024, respectively). They also experienced less pain interference with activities (1.9 ± 1.7 change in score; effect size = 0.83; CI, 0.3–3.4; p = 0.026) when wearing a torsion adapter. However, these patients took a similar number of total steps per day, walked a comparable distance in 6 minutes, and reported similar residual limb pain and fatigue. Conclusions For a moderately active group of amputees, the torsion adapter did not translate to substantial improvements in functional mobility and self-perceived pain and fatigue. The small increases in low- and medium-intensity activities with less pain interference when wearing a torsion adapter provides evidence to support prescribing this device for amputees with difficulty navigating the household and community environments. Level of Evidence Level II, therapeutic study. See Instructions for Authors for a complete description of levels of evidence.

Phantom limb pain (PLP)-pain felt in the amputated limb-is often accompanied by significant suffering. Estimates of the burden of PLP have provided conflicting data. To obtain a robust estimate of the burden of PLP, we gathered and critically appraised the literature on the prevalence and risk factors associated with PLP in people with limb amputations. Articles published between 1980 and July 2019 were identified through a systematic search of the following electronic databases: MEDLINE/PubMed, PsycINFO, PsycArticles, Cumulative Index to Nursing and Allied Health Literature, Africa-Wide Information, Health Source: Nursing/Academic Edition, SCOPUS, Web of Science and Academic Search Premier. Grey literature was searched on databases for preprints. Two reviewers independently conducted the screening of articles, data extraction and risk of bias assessment. The meta-analyses were conducted using the random effects model. A statistically significant level for the analyses was set at p<0.05. The pooling of all studies demonstrated a prevalence estimate of 64% [95% CI: 60.01-68.05] with high heterogeneity [I2 = 95.95% (95% CI: 95.10-96.60)]. The prevalence of PLP was significantly lower in developing countries compared to developed countries [53.98% vs 66.55%; p = 0.03]. Persistent pre-operative pain, proximal site of amputation, stump pain, lower limb amputation and phantom sensations were identified as risk factors for PLP. This systematic review and meta-analysis estimates that six of every 10 people with an amputation report PLP-a high and important prevalence of PLP. Healthcare professionals ought to be aware of the high rates of PLP and implement strategies to reduce PLP by addressing known risk factors, specifically those identified by the current study.

Background Postamputation neuroma pain can prevent comfortable prosthesis wear in patients with limb amputations, and currently available treatments are not consistently effective. Targeted muscle reinnervation (TMR) is a decade-old technique that employs a series of novel nerve transfers to permit intuitive control of upper-limb prostheses. Clinical experience suggests that it may also serve as an effective therapy for postamputation neuroma pain; however, this has not been explicitly studied. Questions/purposes We evaluated the effect of TMR on residual limb neuroma pain in upper-extremity amputees. Methods We conducted a retrospective medical record review of all 28 patients treated with TMR from 2002 to 2012 at Northwestern Memorial Hospital/Rehabilitation Institute of Chicago (Chicago, IL, USA) and San Antonio Military Medical Center (San Antonio, TX, USA). Twenty-six of 28 patients had sufficient (> 6 months) followup for study inclusion. The amputation levels were shoulder disarticulation (10 patients) and transhumeral (16 patients). All patients underwent TMR for the primary purpose of improved myoelectric control. Of the 26 patients included in the study, 15 patients had evidence of postamputation neuroma pain before undergoing TMR. Results Of the 15 patients presenting with neuroma pain before TMR, 14 experienced complete resolution of pain in the transferred nerves, and the remaining patient’s pain improved (though did not resolve). None of the patients who presented without evidence of postamputation neuroma pain developed neuroma pain after the TMR procedure. All 26 patients were fitted with a prosthesis, and 23 of the 26 patients were able to operate a TMR-controlled prosthesis. Conclusions None of the 26 patients who underwent TMR demonstrated evidence of new neuroma pain after the procedure, and all but one of the 15 patients who presented with preoperative neuroma pain experienced complete relief of pain in the distribution of the transferred nerves. TMR offers a novel and potentially more effective therapy for the management of neuroma pain after limb amputation. Level of Evidence Level IV, therapeutic study. See Instructions for Authors for a complete description of levels of evidence.

Background Symptomatic neuroma occurs in 13% to 32% of amputees, causing pain and limiting or preventing the use of prosthetic devices. Targeted nerve implantation (TNI) is a procedure that seeks to prevent or treat neuroma-related pain in amputees by implanting the proximal amputated nerve stump onto a surgically denervated portion of a nearby muscle at a secondary motor point so that regenerating axons might arborize into the intramuscular motor nerve branches rather than form a neuroma. However, the efficacy of this approach has not been demonstrated. Questions/purposes We asked: Does TNI (1) prevent primary neuroma-related pain in the setting of acute traumatic amputation and (2) reduce established neuroma pain in upper- and lower-extremity amputees? Methods We retrospectively reviewed two groups of patients treated by one surgeon: (1) 12 patients who underwent primary TNI for neuroma prevention at the time of acute amputation and (2) 23 patients with established neuromas who underwent neuroma excision with secondary TNI. The primary outcome was the presence or absence of palpation-induced neuroma pain at last followup, based on a review of medical records. The patients presented here represent 71% of those who underwent primary TNI (12 of 17) and 79% of those who underwent neuroma excision with secondary TNI (23 of 29 patients) during the period in question; the others were lost to followup. Minimum followup was 8 months (mean, 22 months; range, 8–60 months) for the primary TNI group and 4 months (mean, 22 months; range, 4–72 months) for the secondary TNI group. Results At last followup, 11 of 12 patients (92%) after primary TNI and 20 of 23 patients (87%) after secondary TNI were free of palpation-induced neuroma pain. Conclusions TNI performed either primarily at the time of acute amputation or secondarily for the treatment of established symptomatic neuroma is associated with a low frequency of neuroma-related pain. By providing a distal target for regenerating axons, TNI may offer an effective strategy for the prevention and treatment of neuroma pain in amputees. Level of Evidence Level IV, therapeutic study. See Instructions for Authors for a complete description of levels of evidence.

Among the leading etiologies of limb amputations are diabetes mellitus, alongside trauma and peripheral vascular disease conditions, whose complications are major indications for surgery, which can subsequently elicit chronic refractory postamputation pain. ‘Phantom limb pain’ (PLP) denotes pain that is perceived as occurring in an absent part of the limb following amputation. Even though it is a relatively common complication among amputees—with an estimated prevalence as high as ~80 percent—the underlying mechanisms of this puzzling condition remain poorly understood. Current theories predominantly emphasize the role of the nervous system and neuropsychopathology in the development of PLP. However, these neurocentric explanations are disputed and have not yet been translated into effective treatments or a definitive cure for the condition, nor have several notable anomalies been settled, which has prompted researchers to call for the exploration of alternative theories. The aim of this paper is to offer an alternative mechanical mechanism for explaining PLP and spontaneous phantom sensations. This work introduces a theoretical model for the mechanism of PLP, drawing on a recent study that proposed this model to explain fibromyalgia-type psychosomatic syndromes as disorders driven by overactive soft tissue myofibroblasts. The manuscript proposes a shift from purely neurocentric models of PLP to a framework where the extracellular matrix and connective tissue, specifically myofascial tissue and inflammatory myofibroblasts—which are often overlooked in research—take part in its pathogenesis. In this suggested model, surgical interventions disrupt the biomechanical stability of the fascio-musculoskeletal biotensegrity-like system, thus acting as a contributing factor in the chronic pain manifestation. The term ‘biotensegrity’ refers to the dynamic biomechanical behavior of a living system that is stabilized by compressive and tensile force elements, a characteristic quality of myofascial tissue. In this framework, abnormal extracellular matrix remodeling, driven by overactive peripheral myofibroblasts, and the concomitant mechanical effects exerted on sensory nerves embedded within the fascia and reaching the neuroma microenvironment contribute to the generation and perception of spontaneous PLP and phantom sensations. The interplay between abnormal extracellular matrix, the neuroma’s intrinsic excitability, as well as peripheral and central neurophysiological mechanisms, collectively provide a biophysical neuropathophysiological basis to help explain PLP. This offers a different unexplored perspective on a condition with poorly understood mechanisms.

Hyperexcitability of N-methyl-D-aspartate (NMDA) receptors may play a role in the persistence of phantom pain. Dextromethorphan (DM) blocks NMDA receptors. Eight cancer and two noncancer amputees with established, disabling phantom pain received oral DM 60 or 90 mg twice daily (BID) in a three-period double-blind crossover placebo-controlled trial. This followed an open-phase trial in which either dose was given three times daily if pain relief during the double-blind phase was <50% of pretreatment intensity. Patients then underwent a 3-month phase of treatment with the best regimen and a subsequent 1-month posttreatment follow-up. All patients reported a >50% decrease in pain intensity, better mood, and lower sedation in each treatment phase. Four individuals reported this level of pain relief with the 60-mg and one with the 90-mg BID regimen during the double-blind phase, whereas two amputees benefited from the 60-mg and three from the 90-mg thrice-daily regimen in the open-phase trial. One reported exacerbation of pain with the 90-mg BID regimen, and three reported pain rebound at the 1-month posttreatment follow-up phase. Three patients stopped all previous analgesic use during the study. Persistent phantom pain probably involves NMDA receptor hyperexcitability because DM 120 to 270 mg/day mitigated the pain satisfactorily.

Background and Objectives: The experience of unpleasant sensory phenomena after lower limb amputations (LLAs), including phantom limb pain (PLP), phantom limb sensation (PLS), and residual limb pain (RLP), impacts global healthcare and adversely affects outcomes post-amputation. This study aimed to describe the distribution of PLP, PLS, and RLP among patients with LLAs registered in the Heidelberg Amputation Registry. The primary objective was to determine the prevalence of sensory abnormalities across different amputation levels and causes. Materials and Methods: In this single-center, cross-sectional study, data from 459 patients registered in the Heidelberg Amputation Registry were analyzed for the occurrence of PLP, PLS and RLP. Subsequently, logistic regression models were used to identify the independent risk factors associated with sensory disturbances following LLAs. The mean age of the LLA patients (31% female, 69% male) was 58 years (SD ± 18). Results: The patients were, on average, 44 years old (SD ± 22) at the time of amputation, with a mean duration since amputation of 15 years (SD ± 17). Transtibial amputations were the most common (43%), followed by transfemoral (39%) and partial foot amputations (10%). Hip and knee disarticulations were observed in 3.7% and 3.5% of the cohort, respectively, with hemipelvectomies accounting for 1%. Traumatic injuries (32%) and neoplastic disorders (22%) were the leading causes of LLAs, while peripheral artery disease and diabetes were responsible for 12% and 6% of cases, respectively. Importantly, a significant proportion of participants (85%) reported experiencing abnormal sensations. The prevalence rates for phantom limb pain (PLP), phantom limb sensation (PLS), and residual limb pain (RLP) were 58%, 66%, and 46%, respectively. The occurrence of sensory disturbances, with the exception of RLP, was significantly affected by the level of amputation. Notably, the age at amputation emerged as an independent risk factor for developing abnormal sensations, including PLS. Conclusions: In conclusion, this study provides a comprehensive overview of sensory abnormalities in a diverse cohort of LLA patients, highlighting the age at amputation as an important factor. The findings emphasize the role of comprehensive registries in enhancing care for individuals with amputations and guiding targeted pain management strategies.