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Objective: To explore the relationship between sociodemographic, clinical, and neurophysiological variables and health-related quality of life (HR-QOL) of patients with phantom limb pain (PLP)., Methods: This is a cross-sectional analysis of a previous clinical trial. Univariate and multivariate linear and logistic regression analyses were used to model the predictors of HR-QOL. We utilized a sequential modeling approach with increasing adjustment levels, controlling for age and sex, and other relevant clinical variables (time since amputation, level of amputation, and pain). HR-QOL was assessed by the SF-36 Health Survey and its 8 subdomains., Results: We analyzed baseline data from 92 patients with lower-limb amputations. They were mostly male (63%), 45.2 ± 15.6 years, with a mean time since amputation of 82.7 ± 122.4 months, and an overall SF-36 score of 55.9 ± 21.5. We found an association between intracortical facilitation (ICF) in the affected hemisphere, gabapentin usage, and HR-QOL. ICF is a predictor of better HRQOL, whereas gabapentin usage was associated with a poorer HR-QOL, with the main model explaining 13.4% of the variance in the outcome. For the SF-36 subdomains, ICF was also a positive predictor for social functioning, bodily pain, and vitality, while medication usage was associated with lower scores in mental health, general health perception, bodily pain, and vitality., Conclusion: We found firsthand 2 new independent predictors of HR-QOL in individuals with PLP, namely, the neurophysiological metric ICF and gabapentin usage. These results highlight the role of the motor cortex excitability in the HR-QOL and stress the need for treatments that favor the neuroplastic adaptation after amputation, for which ICF may be used as a possible marker., (© The Author(s) 2024. Published by Oxford University Press on behalf of the American Academy of Pain Medicine. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Despite the increasing incidence and prevalence of amputation across the globe, individuals with acquired limb loss continue to struggle with functional recovery and chronic pain. A more complete understanding of the motor and sensory remodeling of the peripheral and central nervous system that occurs postamputation may help advance clinical interventions to improve the quality of life for individuals with acquired limb loss. The purpose of this article is to first provide background clinical context on individuals with acquired limb loss and then to provide a comprehensive review of the known motor and sensory neural adaptations from both animal models and human clinical trials. Finally, the article bridges the gap between basic science researchers and clinicians that treat individuals with limb loss by explaining how current clinical treatments may restore function and modulate phantom limb pain using the underlying neural adaptations described above. This review should encourage the further development of novel treatments with known neurological targets to improve the recovery of individuals postamputation. Significance Statement In the United States, 1.6 million people live with limb loss; this number is expected to more than double by 2050. Improved surgical procedures enhance recovery, and new prosthetics and neural interfaces can replace missing limbs with those that communicate bidirectionally with the brain. These advances have been fairly successful, but still most patients experience persistent problems like phantom limb pain, and others discontinue prostheses instead of learning to use them daily. These problematic patient outcomes may be due in part to the lack of consensus among basic and clinical researchers regarding the plasticity mechanisms that occur in the brain after amputation injuries. Here we review results from clinical and animal model studies to bridge this clinical-basic science gap., (Copyright © 2023 the authors.)

Purpose of Review: Chronic postamputation pain (cPAP) remains a clinical challenge, and current understanding places a high emphasis on prevention strategies. Unfortunately, there is still no evidence-based regimen to reliably prevent chronic pain after amputation., Recent Findings: Risk factors for the development of phantom limb pain have been proposed. Analgesic preventive interventions are numerous and no silver bullet has been found. Novel techniques such as neuromodulation and cryoablation have been proposed. Surgical techniques focusing on reimplantation of the injured nerve might reduce the incidence of phantom limb pain after surgery., Summary: Phantom limb pain is a multifactorial process involving profound functional and structural changes in the peripheral and central nervous system. These changes interact with individual medical, psychosocial and genetic patient risk factors. The patient collective of amputees is very heterogeneous. Available evidence suggests that efforts should focus on prevention of phantom limb pain, since treatment is notoriously difficult. Questions as yet unanswered include the evidence-base of specific analgesic interventions, their optimal "window of opportunity" where they may be most effective, and whether patient stratification according to biopsychosocial risk factors can help guide preventive therapy., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Introduction: We previously reported that a 6-day continuous peripheral nerve block reduces established postamputation phantom pain. To provide patients and providers with the information to best inform treatment decisions, here we reanalyze the data and present the results in a more patient-centered format. We also provide information on patient-defined clinically relevant benefits to facilitate evaluation of available studies and guide future trial design., Methods: The original trial enrolled participants with a limb amputation and phantom pain who were randomized to receive a 6-day continuous peripheral nerve block(s) of either ropivacaine (n=71) or saline (n=73) in a double-masked fashion. Here we calculate the percentage of each treatment group that experienced a clinically relevant improvement as defined by previous studies as well as present what the participants of our study defined as small, medium, and large analgesic improvements using the 7-point ordinal Patient Global Impression of Change scale., Results: Among patients who were given a 6-day ropivacaine infusion, 57% experienced at least a 2-point improvement on the 11-point numeric rating scale in their average and worst phantom pain 4 weeks postbaseline as compared with 26% (p<0.001) for average and 25% (p<0.001) for worst pain in patients given a placebo infusion. At 4 weeks, the percentage of participants rating their pain as improved was 53% for the active vs 30% for the placebo groups (95% CI 1.7 (1.1, 2.7), p = 0.008). For all patients combined, the median (IQR) phantom pain Numeric Rating Scale improvements at 4 weeks considered small, medium, and large were 2 (0-2), 3 (2-5), and 5 (3-7), respectively. The median improvements in the Brief Pain Inventory interference subscale (0-70) associated with small, medium, and large analgesic changes were 8 (1-18), 22 (14-31), and 39 (26-47)., Conclusions: Among patients with postamputation phantom pain, a continuous peripheral nerve block more than doubles the chance of a clinically relevant improvement in pain intensity. Amputees with phantom and/or residual limb pain rate analgesic improvements as clinically relevant similarly to other chronic pain etiologies, although their smallest relevant improvement in the Brief Pain Inventory was significantly larger than previously published values., Trial Registration Number: NCT01824082., Competing Interests: Competing interests: BMI and BK: The University of California has received funding and/or equipment for other research projects from Epimed International (Dallas, TX), Infutronics (Natick, MA), Avanos (Irvine, CA), and SPR Therapeutics (Cleveland, OH). DIS: Chair Data and Safety Monitoring Board, Neuros Medical QUEST trial. Consultant for Pacira Pharmaceuticals (Parsippany, NJ), and this company funds trials in the Department of Outcomes Research. SPC: receives research funding (paid to the institution) from Avanos (Irvine, CA), and research funding (paid to the institution) from Scilex (San Diego, CA). He serves as a consultant for SPR Therapeutics (Cleveland, OH). AT: Pacira Pharmaceuticals (Parsippany, NJ) funds trials in the Department of Outcomes Research., (© American Society of Regional Anesthesia & Pain Medicine 2023. Re-use permitted under CC BY-NC. No commercial re-use. Published by BMJ.)

Objective: Painful Phantom Limb Syndrome (PPLS) occurs in 50 to 80% of patients undergoing amputation, having a great impact on quality of life, productivity and psychosocial sphere. The objective of this review is to summarize the pharmacological and non-pharmacological strategies, surgical optimization, and provide a multidisciplinary approach aimed at reducing the incidence of chronic pain associated with PPLS in patients undergoing limb amputation., Methods: A narrative review was carried out using Medline, Pubmed, Proquest, LILACS and Cochrane, searching for articles between 2000 and 2021. Articles describing the epidemiology, pathophysiological considerations, and current treatments were selected after a screening process., Results: A multidisciplinary and multimodal approach is required in PPLS, and should include the use of regional techniques, and adjuvants such as NSAIDs, ketamine, lidocaine and gabapentinoids. In addition, an evaluation and continuous management of risk factors for chronic pain in conjunction with the surgical team is necessary., Conclusion: The current literature does not support that a single technique is effective inthe prevention of PPLS. However, adequate acute pain control, rehabilitation and early restoration of the body scheme under a multidisciplinary and multimodal approach have shown benefit in the acute setting.

Introduction: Phantom 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 Presentation: A 36-year-old African male with acute phantom limb pain in the left lower limb, was treated with transcutaneous electrical nerve stimulation., Conclusion: The 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., (© 2023. The Author(s).)

Objectives: Randomised controlled trial of the effect of a perineural infusion of levobupivacaine on moderate/severe phantom limb pain 6 months after major lower limb amputation., Setting: Single-centre, UK university hospital., Participants: Ninety 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., Interventions: Either 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 Measures: The 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., Results: Data 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., Conclusions: Long-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 Numbers: EudraCT 2007-000619-27; ISRCTN68691928., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Postamputation phantom pain is notoriously persistent with few validated treatments. Cryoneurolysis involves the application of low temperatures to reversibly ablate peripheral nerves. The authors tested the hypothesis that a single cryoneurolysis treatment would decrease phantom pain 4 months later., Methods: The authors enrolled patients with a lower-limb amputation and established phantom pain. Each received a single-injection femoral and sciatic nerve block with lidocaine and was subsequently randomized to receive either ultrasound-guided percutaneous cryoneurolysis or sham treatment at these same locations. The primary outcome was the change in average phantom pain intensity between baseline and 4 months as measured with a numeric rating scale (0 to 10), after which an optional crossover treatment was offered. Investigators, participants, and clinical staff were masked to treatment group assignment with the exception of the treating physician performing the cryoneurolysis, who had no subsequent participant interaction., Results: Pretreatment phantom pain scores were similar in both groups, with a median [quartiles] of 5.0 [4.0, 6.0] for active treatment and 5.0 [4.0, 7.0] for sham. After 4 months, pain intensity decreased by 0.5 [-0.5, 3.0] in patients given cryoneurolysis (n = 71) versus 0 [0, 3] in patients given sham (n = 73), with an estimated difference (95% CI) of -0.1 (-1.0 to 0.7), P = 0.759. Following their statistical gatekeeping protocol, the authors did not make inferences or draw conclusions on secondary endpoints. One serious adverse event occurred after a protocol deviation in which a femoral nerve cryolesion was induced just below the inguinal ligament-instead of the sensory-only saphenous nerve-which resulted in quadriceps weakness, and possibly a fall and clavicle fracture., Conclusions: Percutaneous cryoneurolysis did not decrease chronic lower extremity phantom limb pain 4 months after treatment. However, these results were based upon the authors' specific study protocol, and since the optimal cryoneurolysis treatment parameters such as freeze duration and anatomic treatment location remain unknown, further research is warranted., (Copyright © 2022, the American Society of Anesthesiologists. All Rights Reserved.)

Background and Objective: Phantom limb pain (PLP) concerns >50% of amputees and has a negative impact on their rehabilitation, mental health and quality of life. Mirror therapy (MT) is a promising strategy, but its effectiveness remains controversial. We performed a systematic review to: (i) evaluate the effectiveness of MT versus placebo in reducing PLP, and (ii) determine MT effect on disability and quality of life., Databases and Data Treatment: We selected randomized-controlled trials in five databases (Medline, Cochrane Library, CINAHL, PEDro and Embase) that included patients with unilateral lower or upper limb amputation and PLP and that compared the effects on PLP of MT versus a placebo technique. The primary outcome was PLP intensity changes and the secondary outcomes were PLP duration, frequency, patients' disability and quality of life., Results: Among the five studies included, only one reported a significant difference between the MT group and control group, with a positive MT effect at week 4. Only one study assessed MT effect on disability and found a significant improvement in the MT group at week 10 and month 6., Conclusions: Our systematic review did not allow concluding that MT reduces PLP and disability in amputees. This lack of strong evidence is probably due to (i) the low methodological quality of the included studies, and (ii) the lack of statistical power. Future trials should include a higher number of patients, increase the number and frequency of MT sessions, have a long-term follow-up and improve the methodological quality., Significance: Recent meta-analyses concluded that MT is effective for reducing phantom limb pain. Conversely, the present systematic review that included only studies with the best level of evidence did not find any evidence about its effectiveness for this condition. We identified many ways to improve future randomized-controlled trials on this topic: increasing the number of participants, reducing the intra-group heterogeneity, using a suitable placebo and intensifying the MT sessions and frequency., (© 2022 The Authors. European Journal of Pain published by John Wiley & Sons Ltd on behalf of European Pain Federation - EFIC ®.)

Introduction: Phantom limb pain (PLP) is a type of neuropathic pain that affects the territory of an amputated limb or other surgically removed body parts. Between 60% and 90% of amputees suffer from PLP during follow-up. There are a range of therapeutic options for PLP, both pharmacological (gabapentin, amitriptyline, tricyclic antidepressants, etc) and non-pharmacological (transcutaneous electrical nerve stimulation, hypnosis, acupuncture, etc). A widely accepted hypothesis considers PLP to be the consequence of postamputation cortical reorganisation. New treatment approaches, such as mirror therapy (MT), have been developed as a result of Ramachandran's groundbreaking research in the 1990s. This review analyses the current evidence on the efficacy of MT for treating PLP., Development: We performed a literature review of publications registered from 2012 to 2017 on the CINAHL, Cochrane, Scopus, and PubMed (including Medline) databases Using the descriptors "phantom limb‿ and "mirror therapy.‿ We identified 115 publications addressing MT in PLP. Of these, 17 (15%) contributed useful information for pooled analysis., Conclusions: MT seems to be effective in relieving PLP, reducing the intensity and duration of daily pain episodes. It is a valid, simple, and inexpensive treatment for PLP. The methodological quality of most publications in this field is very limited, highlighting the need for additional, high-quality studies to develop clinical protocols that could maximise the benefits of MT for patients with PLP., (Copyright © 2018 Sociedad Española de Neurología. Publicado por Elsevier España, S.L.U. All rights reserved.)

Introduction: Phantom limb pain (PLP) is a type of neuropathic pain that affects the territory of an amputated limb or other surgically removed body parts. Between 60% and 90% of amputees suffer from PLP during follow-up. There are a range of therapeutic options for PLP, both pharmacological (gabapentin, amitriptyline, tricyclic antidepressants, etc) and non-pharmacological (transcutaneous electrical nerve stimulation, hypnosis, acupuncture, etc). A widely accepted hypothesis considers PLP to be the consequence of postamputation cortical reorganisation. New treatment approaches, such as mirror therapy (MT), have been developed as a result of Ramachandran's groundbreaking research in the 1990s. This review analyses the current evidence on the efficacy of MT for treating PLP., Development: We performed a literature review of publications registered from 2012 to 2017 on the CINAHL, Cochrane, Scopus, and PubMed (including Medline) databases using the descriptors "phantom limb" and "mirror therapy." We identified 115 publications addressing MT in PLP. Of these, 17 (15%) contributed useful information for pooled analysis., Conclusions: MT seems to be effective in relieving PLP, reducing the intensity and duration of daily pain episodes. It is a valid, simple, and inexpensive treatment for PLP. The methodological quality of most publications in this field is very limited, highlighting the need for additional, high-quality studies to develop clinical protocols that could maximise the benefits of MT for patients with PLP., (Copyright © 2018 Sociedad Española de Neurología. Published by Elsevier España, S.L.U. All rights reserved.)

Background: We recently reported that a 6-day continuous peripheral nerve block reduced established postamputation phantom pain 3 weeks after treatment ended. However, the immediate effects of perineural infusion (secondary outcomes) have yet to be reported., Methods: Participants from 5 enrolling academic centers with an upper or lower limb amputation and established phantom pain received a single-injection ropivacaine peripheral nerve block(s) and perineural catheter insertion(s). They were subsequently randomized to receive a 6-day ambulatory perineural infusion of either ropivacaine 0.5% or normal saline in a double-masked fashion. Participants were contacted by telephone 1, 7, 14, 21, and 28 days after the infusion started, with pain measured using the Numeric Rating Scale. Treatment effects were assessed using the Wilcoxon rank-sum test at each time point. Adjusting for 4 time points (days 1, 7, 14, and 21), P < .0125 was deemed statistically significant. Significance at 28 days was reported using methods from the original, previously published article., Results: Pretreatment average phantom and residual pain scores were balanced between the groups. The day after infusion initiation (day 1), average phantom, and residual limb pain intensity was lower in patients receiving local anesthetic (n = 71) versus placebo (n = 73): median [quartiles] of 0 [0-2.5] vs 3.3 [0-5.0], median difference (98.75% confidence interval [CI]) of -1.0 (-3.0 to 0) for phantom pain (P = .001) and 0 [0-0] vs 0 [0-4.3], and median difference 0.0 (-2.0 to 0.0) for residual limb pain (P < .001). Pain's interference with physical and emotional functioning as measured with the interference domain of the Brief Pain Inventory improved during the infusion on day 1 for patients receiving local anesthetic versus placebo: 0 [0-10] vs 10 [0-40], median difference (98.75% CI) of 0.0 (-16.0 to 0.0), P = .002. Following infusion discontinuation (day 6), a few differences were found between the active and placebo treatment groups between days 7 and 21. In general, sample medians for average phantom and residual limb pain scores gradually increased after catheter removal for both treatments, but to a greater degree in the control group until day 28, at which time the differences between the groups returned to statistical significance., Conclusions: This secondary analysis suggests that a continuous peripheral nerve block decreases phantom and residual limb pain during the infusion, although few improvements were again detected until day 28, 3 weeks following catheter removal., Competing Interests: Conflicts of Interest: See Disclosures at the end of the article., (Copyright © 2021 International Anesthesia Research Society.)

The purpose of this study is to describe the results of clonazepam use in the treatment of phantom limb pain (PLP). Although the efficacy of clonazepam on PLP has been reported in 1996, there are no subsequent known studies that confirmed this report. A consecutive sample of 32 patients who suffered from PLP after recent lower limb amputation was studied based on clinical charts. Wilcoxon's signed rank test was used to compare Numeric Rating Scale (NRS) values before and after the treatment with clonazepam. Twenty-three amputees were treated only with clonazepam, without adding other drugs or targeted rehabilitation treatments. The median NRS before the treatment with clonazepam was 7 (2), the median NRS after 31 ± 5 days of treatment was 3 (3.5) ( p < 0.0001). The average dosage of clonazepam used was 1.5 ± 1 mg per day. The results suggest that clonazepam has to be considered as an alternative drug for PLP treatment., Competing Interests: There are no conflicts of interest., (Copyright © 2021 Stefano Brunelli et al.)

Abstract: A 36-yr-old man with a history of industrial accident causing traumatic left hip disarticulation, pubic symphysis, and right sacroiliac joint fractures presented with a 3-yr history of left-sided lower back pain radiating down the amputated limb. Computed tomography lumbar spine showed osteophytes surrounding the sacroiliac joint bilaterally with reduced left L4-L5 foraminal space. A fluoroscopically guided left sacroiliac steroid injection led to mild improvement in low back pain. Magnetic resonance imaging of the lumbar spine without contrast showed transitional type L5 vertebral body with left-sided flowing osteophytes abutting the extraforaminal L4 and L5 nerves. Ultimately, multilevel left fluoroscopically guided transforaminal epidural steroid injection at L4-L5 and L5-S1 significantly improved symptoms. Although phantom radiculopathy is a rare entity, clinical suspicion of degenerative spine disease or other pathology contributing to nerve impingement in patients with amputations should remain; this unique case discusses bony osteophyte complex as the cause for phantom radiculopathy instead of previously described disc herniation. Magnetic resonance imaging remains a key tool in delineating causes of low back pain among patients with lower limb amputations., Competing Interests: Financial disclosure statements have been obtained, and no conflicts of interest have been reported by the authors or by any individuals in control of the content of this article., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)

Phantom limb pain is thought to be sustained by reentrant neural pathways, which provoke dysfunctional reorganization in the somatosensory cortex. We hypothesized that disrupting reentrant pathways with a 6-day-long continuous peripheral nerve block reduces phantom pain 4 weeks after treatment. We enrolled patients who had an upper- or lower-limb amputation and established phantom pain. Each was randomized to receive a 6-day perineural infusion of either ropivacaine or normal saline. The primary outcome was the average phantom pain severity as measured with a Numeric Rating Scale (0-10) at 4 weeks, after which an optional crossover treatment was offered within the following 0 to 12 weeks. Pretreatment pain scores were similar in both groups, with a median (interquartile range) of 5.0 (4.0, 7.0) for each. After 4 weeks, average phantom limb pain intensity was a mean (SD) of 3.0 (2.9) in patients given local anesthetic vs 4.5 (2.6) in those given placebo (difference [95% confidence interval] 1.3 [0.4, 2.2], P = 0.003). Patients given local anesthetic had improved global impression of change and less pain-induced physical and emotional dysfunction, but did not differ on depression scores. For subjects who received only the first infusion (no self-selected crossover), the median decrease in phantom limb pain at 6 months for treated subjects was 3.0 (0, 5.0) vs 1.5 (0, 5.0) for the placebo group; there seemed to be little residual benefit at 12 months. We conclude that a 6-day continuous peripheral nerve block reduces phantom limb pain as well as physical and emotional dysfunction for at least 1 month., (Copyright © 2020 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the International Association for the Study of Pain.)

Neuropathic opioid refractory phantom limb pain (PLP) following amputation can be a life long debilitating chronic pain syndrome capable of completely destroying a patient's life. The pain, its associated depression and sleep deprivation can make many patients suicidal. Ever changing and relentless, it is notoriously unresponsive to traditional cocktails of strong opioids, adjuvant pain medications, antidepressants, local anaesthetics, nerve stimulators, hypnotics and psychotropics. Drug effects are seldom more effective than placebo. We describe a successful sustained rescue of a difficult 2-year-long PLP case with sublingual buprenorphine/naloxone using the drug's potent multimodal mechanisms of action: potent long-acting mu agonist/antagonist, kapa receptor antagonist, delta receptor antagonist and novel opioid receptor-like 1 (OR-L1) agonist effects. Traditional escalating pure mu-opioid receptor agonists and adjuvant neuropathic pain cocktails often have disappointing efficacy in the treatment of resistant PLP. We suggest introducing buprenorphine/naloxone as an early effective opioid choice in PLP management., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2021. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Phantom limb pain (PLP) is a prevalent problem for children after amputation because of the chemotherapy treatment. Gabapentin is a potential option to manage PLP after amputation in pediatric oncology. However, no systematic review specifically investigated this topic. Thus, this study aims to appraise the efficacy and safety of gabapentin for post-amputation PLP in pediatric oncology., Methods: Electronic databases (Cochrane Library, MEDLINE, EMBASE, Web of Science, CINAHL, PsychINFO, Scopus, WANGFANG, and Chinese Biomedical Literature Database) will be systematically searched from the beginning to the present without limitations to publication status and language. Primary outcome is pain intensity. Secondary outcomes are analgesic drug consumption, sleep quality, depression, anxiety, health-related quality of life, and adverse events. The treatment effect of all dichotomous outcome data will be estimated as risk ratio and 95% confidence intervals (CIs) and that of continuous outcome data will be calculated as mean difference or standardized mean difference and 95% CIs. Methodological quality of randomized controlled trials (RCTs) will be assessed using Cochrane risk of bias tool and that of case-controlled studies (CCSs) will be appraised using Newcastle-Ottawa Tool. Statistical analysis will be conducted using RevMan 5.3 software., Discussion: This study will summarize up-to-date high-quality RCTs and CCSs to assess the efficacy and safety of gabapentin for PLP after amputation in pediatric oncology. The findings of this study will help to determine whether or not gabapentin is effective and safe for children with PLP after amputation., Systematic Review Registration: INPLASY202060090.

Prevention of phantom limb pain is one of the biggest and still largely unsolved challenges in perioperative medicine. Despite many study efforts and optimization of postoperative pain treatment over the last 30 years, a significant reduction in the incidence of phantom limb pain has not been achieved. Current studies have also shown that at least 50% of patients develop phantom pain after 6 months. A possible approach could be to combine multiple synergistic interventions and implement them as a perioperative phantom pain management strategy bundle. In addition to regional anesthesia, NMDA antagonists, gabapentinoids, antidepressants and systemic lidocaine could play a relevant role. The aim of this pharmacological intervention was the modification of the pathophysiological changes in peripheral nerves and in the central nervous system after amputation.

Limb amputations are carried out for a number of reasons, which include trauma, vascular disorders, infection, oncology and congenital abnormalities. These patients can develop multiple complications postoperatively with phantom limb pain being a well-recognised issue. That being said, phantom radiculopathy is far less encountered and can therefore be easily overlooked. There are limited cases described in literature and as a result pathophysiology is poorly understood. In this report, we present a patient who had developed phantom radiculopathy decades after his left above knee amputation surgery, which was performed after a road traffic accident. However, we were successfully able to treat the patient with foraminal epidural corticosteroid injection., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2020. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Patients who have limb amputation are at risk of chronic pain, including phantom limb pain that can be challenging to treat. The aim of this study was to describe the incidence of pre-operative opioid usage and the incidence and risk factors for new persistent post-operative opioid usage in opioid-naïve patients after limb amputation., Methods: A retrospective study of all patients 18 years and older underwent upper or lower extremity amputations in Landspitali University Hospital between 2005 and 2015. Patients were considered to use opioids pre-operatively if they filled an opioid prescription 1-6 months prior to amputation and were considered to have persistent opioid use if opioid prescriptions were filled between post-operative months four to twenty-four. In addition to incidence estimate, uni- and multivariate analysis was performed to identify risk factors for persistent post-operative opioid usage., Results: Of 328 total patients, 216 (66%) were opioid naïve and 112 (34%) were chronic opioid users. Of the opioid-naïve patients surviving more than 3 months 40 (20%) developed persistent post-operative opioid usage. In multivariate analysis, factors independently associated with persistent post-operative opioid usage were younger age, male gender, pre-operative use of neuropathic medications or benzodiazepines and lower (opposed to upper) extremity amputation., Conclusion: Opioid naïve patients undergoing major amputation had a 20% chance of having a persistent opioid requirement following surgery. This could represent new-onset phantom limb pain or other chronic pain. Our findings should encourage perioperative multimodal efforts to reduce the burden of chronic pain after limb amputations., (© 2019 The Acta Anaesthesiologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.)

In this randomized, double-blind, placebo-controlled crossover study, we investigated whether a peripheral nerve block could temporarily eliminate phantom and stump pain after amputation. Amputees with constant postamputation pain were included and randomized to receive a nerve block with lidocaine 2% with adrenaline or saline in a crossover design. Spontaneous phantom and stump pain and evoked responses were assessed at baseline and at fixed time-points until 120 minutes after lidocaine or saline injection. The primary outcome was the difference in absolute change between worst pain intensity, either phantom or stump pain, at baseline and at 30 minutes after lidocaine or saline injection. Twelve amputees were randomized and 9 patients were included in the analysis. The absolute change in median worst pain intensity between lidocaine and saline injection was -2.0 (interquartile range, -4.0 to 0.0) (n = 9, P = 0.12). Nine of 9 patients reported at least some pain relief after lidocaine injection compared with only 2 of 9 patients after saline injection (P = 0.02). Phantom pain intensity was significantly reduced after lidocaine compared with saline injection (P = 0.04), whereas there was no significant change in stump pain intensity between the 2 interventions (P = 0.17). In all 9 amputees, evoked responses were eliminated after lidocaine injection. Thus, our findings suggest that afferent input from the peripheral nervous system plays an important role in postamputation pain.

Phantom limb (PLP) as well as residual limb pain (RLP) are still a very significant problem after amputation and their causes are only partially known. Here we tested whether the predisposition for the frequency, duration and intensity of PLP and RLP is shared with other prior chronic pains and/or the presence of postamputation subacute pain. A week preoperatively we collected data using validated questionnaires, a pain diary and interviews on past chronic pain conditions, acute pain, depression, anxiety, pain interference, life control, social support and affective distress and pain ratings one day before the amputation in 52 patients scheduled for limb amputation. In the week postamputation and again three and 12 months thereafter, we collected data on postoperative wound pain, PLP, RLP and non-painful phantom sensation (PLS). Phantom and residual limb pain indices were calculated per patient, integrating the intensity, frequency and duration of past chronic pain, PLP, RLP and PLS into a single value to index the overall burden of pain. We report that acute and chronic pain long before but not on the day before the amputation and subacute pain postamputation significantly predicted up to half of the variance in the incidence and severity of PLP, RLP and PLS 12 months postamputation. Moreover, the severity of these painful sensations at 12 months postamputation was partially predicted by preamputation scores of depression and anxiety. These findings corroborate the hypothesis that chronic pain and non-painful sensations following limb amputation are strongly related to longstanding preoperative chronic pain and to subacute postoperative pain as well as to psychological factors before the amputation that may be inherited and/or acquired (learning- and memory-related). Furthermore, we also confirm that subacute pain postamputation comprises an additional risk factor for long-term painful sensations postamputation. Our results suggest that timely interventions might prevent the development of chronic pain., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Background and Purpose: The purpose of this case report is to describe a multimodal pain therapeutic concept including the adjunct use of pregabalin in a 4.5 year-old child after forefoot amputation. Phantom limb pain and sensation is a complex pain syndrome that is difficult to treat and prevent. 70-75% of all children develop such a pain syndrome after amputation. We describe here a paediatric patient who underwent forefoot amputation following traumatic foot injury and received multimodal pain therapy including pregabalin., Methods: A 4.5 year-old otherwise healthy girl suffered severe injuries of the right foot and lower leg during a motor vehicle accident. Due to development of severe necrosis, forefoot amputation had to be performed during the hospital stay., Results: Initial pain therapy included paracetamol, ibuprofen, metamizol, morphine and fentanyl. With mounting pain and anxiety, regional anaesthesia of the distal sciatic nerve was administered in combination with a ketamine and morphine patient controlled analgesia pump (PCA). The peripheral blockade of the distal sciatic nerve was placed with the guidance of ultrasound and nerve stimulator. The PCA concept included a continuous basal rate combined with a bolus function. Although the regional anaesthesia was well positioned and functioning, there was inadequate pain control. The pain was described by the patient as short, highly intense and sharp sensations with intensity on the visual analogue scale (VAS) of 10 (out of 10). Furthermore, she suffered from anxiety episodes and sleep disturbance. The medical team decided to treat with pregabalin to resolve these issues while awaiting amputation (Lisfranc line). She received psychological counselling as adjunct treatment. This multimodal concept enabled an early and efficient pain reduction pre- and post-amputation and allowed for the possibility of a hospital discharge without any opioid pain medication., Conclusion: The multimodal pain therapy including pregabalin was well tolerated, safe and highly effective in this case of traumatic limb injury and subsequent amputation. The use of pregabalin allowed significant pain and anxiety reduction for the patient., Implications: Pregabalin is frequently used in adult patients for severe complex pain syndromes. There are only few reports of such adjunct medication (pregabalin) in paediatric pain syndromes. These reports focus mainly on the paediatric oncologic population. The case reported here encourages physicians to consider adjunct medications when treating complex pain, which are well established in the adult population. The benefits of such therapy in complex pain and anxiety can be extended to the paediatric population in select cases. Of course, one must always take into account that many routine medications used in children are well established but are off-label use. The authors are well aware of this problem and have conducted a critical literature review prior to pregabalin administration, including the search for randomized trials examining safety and tolerability. The parents or legal guardians of a minor must be thoroughly informed and consent to such a constellation of medical treatment., (Copyright © 2017 Scandinavian Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.)

A case is presented of a 54-year old patient who had been treated 10 months previously with enucleation for a painful blind eye. This led to severe and chronic pain in the orbital region that did not respond to conventional pain management. However, a single 1.5 ml injection of 96 % ethanol led to almost complete resolution of pain for the follow-up period of 6 months. Orbital pain after enucleation or evisceration may originate from the implant itself, the prosthesis, the socket or the sinuses. Taking a careful medical history and an examination, including orbital scans, are necessary to decide on the correct differential diagnosis. If any pathology is excluded, one should keep in mind that phantom pain in the orbit seems common after removing an eye, more often when pain originating from the ball and/or headache was present before removal. The management of chronic pain in the orbital region has received little attention. Retrobulbar alcohol injection still has a place in modern ophthalmology, because it delivers effective pain relief in certain chronic conditions., (Georg Thieme Verlag KG Stuttgart · New York.)

Deafferentation pain induced by subarachnoid block (SAB) is rare, but it can appear in the form of recurrent phantom lower limb pain, new acute-onset stump pain in amputees, lower limb pain in patients with tabes dorsalis, and neuropathic pain. We have previously reported that thiopental is an effective treatment for deafferentation pain induced by therapeutic SAB applied to treat neuropathic pain of central origin. Here, we report the case of an amputee who developed new stump pain in his lower limb immediately after subarachnoid tetracaine was administered prior to appendectomy. A 51-year-old man who had previously undergone right below-knee amputation for acute arterial thrombosis, and who had not previously experienced chronic phantom limb or stump pain, was scheduled for emergency open appendectomy. For anesthesia, we induced SAB with a hyperbaric tetracaine solution. No paresthesia occurred during administration. However, the patient immediately complained of severe, lightning-bolt pain in the right lower limb stump after the SAB was established. He was given intravenous pentazocine, which promptly resolved the pain. Appendectomy was then performed under sedation using intravenous midazolam. The patient did not experience further deafferentation pain during his hospital stay and has reported no stump pain since discharge from the hospital. This case report suggests that SAB induces deafferentation pain in some patients and that this unusual pain can be treated with pentazocine.

Phantom limb pain (PLP) occurs in up to 85% of patients who have undergone an amputation and remains difficult to treat. Memantine is a N-Methyl-d-aspartate receptor antagonist that has shown benefit in pain syndromes. The objective of this systematic review is to evaluate the evidence for the use of memantine in the treatment of acute and chronic PLP. MEDLINE (1956 to May 2016) and Embase (1957 to May 2016) were queried for articles that characterized the clinical outcomes of patient(s) treated with memantine for PLP. The initial search identified 185 studies and case reports. After screening, eight articles were included. One prospective study, a case report, and two case series demonstrated benefit with memantine in the treatment of acute PLP. However, in chronic PLP that persisted for over 1 year, four prospective studies failed to demonstrate significant analgesic effects with memantine. Memantine was well tolerated in all studies. Memantine appears to be a reasonable option to trial in a patient with a recent amputation or who has failed or cannot tolerate other analgesics. Additional research is needed to further determine the role of memantine in the treatment and prevention of PLP and to identify the population most likely to gain benefit.

Background: This is an updated version of the original Cochrane review published in Issue 12, 2011. Phantom limb pain (PLP) is pain that arises in the missing limb after amputation and can be severe, intractable, and disabling. Various medications have been studied in the treatment of phantom pain. There is currently uncertainty in the optimal pharmacologic management of PLP., Objectives: This review aimed to summarise the evidence of effectiveness of pharmacologic interventions in treating PLP., Search Methods: For this update, we searched the Cochrane Central Register of Controlled Trials (CENTRAL, the Cochrane Library), MEDLINE, and Embase for relevant studies. We ran the searches for the original review in September 2011 and subsequent searches for this update up to April 2016. We sought additional studies from clinical trials databases and reference lists of retrieved papers., Selection Criteria: We included randomised and quasi-randomised trials studying the effectiveness of pharmacologic interventions compared with placebo, another active treatment, or no treatment, in established PLP. We considered the following outcomes: change in pain intensity, function, sleep, depression or mood, quality of life, adverse events, treatment satisfaction, and withdrawals from the study., Data Collection and Analysis: We independently assessed issues of study quality and extracted efficacy and adverse event data. Due to the wide variability in the studies, we did not perform a meta-analysis for all the interventions and outcomes, but attempted to pool the results of some studies where possible. We prepared a qualitative description and narrative summary of results. We assessed clinical heterogeneity by making qualitative comparisons of the populations, interventions, outcomes/outcome measures, and methods., Main Results: We added only one new study with 14 participants to this updated review. We included a 14 studies (10 with low risk of bias and 4 with unclear risk of bias overall) with a total of 269 participants. We added another drug class, botulinum neurotoxins (BoNTs), in particular botulinum toxin A (BoNT/A), to the group of medications reviewed previously. Our primary outcome was change in pain intensity. Most studies did not report our secondary outcomes of sleep, depression or mood, quality of life, treatment satisfaction, or withdrawals from the study.BoNT/A did not improve phantom limb pain intensity during the six months of follow-up compared with lidocaine/methylprednisolone.Compared with placebo, morphine (oral and intravenous) was effective in decreasing pain intensity in the short term with reported adverse events being constipation, sedation, tiredness, dizziness, sweating, voiding difficulty, vertigo, itching, and respiratory problems.The N-methyl D-aspartate (NMDA) receptor antagonists ketamine (versus placebo; versus calcitonin) and dextromethorphan (versus placebo), but not memantine, had analgesic effects. The adverse events of ketamine were more serious than placebo and calcitonin and included loss of consciousness, sedation, hallucinations, hearing and position impairment, and insobriety.The results for gabapentin in terms of pain relief were conflicting, but combining the results favoured treatment group (gabapentin) over control group (placebo) (mean difference -1.16, 95% confidence interval -1.94 to -0.38; 2 studies). However, gabapentin did not improve function, depression score, or sleep quality. Adverse events experienced were somnolence, dizziness, headache, and nausea.Compared with an active control benztropine mesylate, amitriptyline was not effective in PLP, with dry mouth and dizziness as the most frequent adverse events based on one study.The findings for calcitonin (versus placebo; versus ketamine) and local anaesthetics (versus placebo) were variable. Adverse events of calcitonin were headache, vertigo, drowsiness, nausea, vomiting, and hot and cold flushes. Most of the studies were limited by their small sample sizes., Authors' Conclusions: Since the last version of this review, we identified another study that added another form of medical therapy, BoNTs, specifically BoNT/A, to the list of pharmacologic interventions being reviewed for clinical efficacy in phantom limb pain. However, the results of this study did not substantially change the main conclusions. The short- and long-term effectiveness of BoNT/A, opioids, NMDA receptor antagonists, anticonvulsants, antidepressants, calcitonins, and local anaesthetics for clinically relevant outcomes including pain, function, mood, sleep, quality of life, treatment satisfaction, and adverse events remain unclear. Based on a small study, BoNT/A (versus lidocaine/methylprednisolone) does not decrease phantom limb pain. Morphine, gabapentin, and ketamine demonstrate favourable short-term analgesic efficacy compared with placebo. Memantine and amitriptyline may not be effective for PLP. However, results must be interpreted with caution, as they were based mostly on a small number of studies with limited sample sizes that varied considerably and also lacked long-term efficacy and safety outcomes. The direction of efficacy of calcitonin, local anaesthetics, and dextromethorphan needs further clarification. Overall, the efficacy evidence for the reviewed medications is thus far inconclusive. Larger and more rigorous randomised controlled trials are needed for us to reach more definitive conclusions about which medications would be useful for clinical practice.

Background: Phantom limb pain (PLP) is a common complication after amputation, affecting up to 80% of the amputee population. However, only 5% to 10% of amputees have severe PLP impacting daily function. The present report details the management of severe, treatment-resistant PLP in a 72-year-old man with a traumatic left transradial amputation and a comorbid complication of heterotopic ossification (HO)., Objective: To describe a case of PLP with HO and the possible role of calcitonin in the treatment of both conditions., Methods: A systematic review of the literature regarding the management of PLP., Results: Seventeen articles that directly addressed PLP were identified; 11 were randomized controlled trials. All involved small samples and follow-up ranged from 6 h to one year, with the majority limited to six weeks., Discussion: In the present case, medication management was limited by side effects, lack of response and the patient's desire to avoid long-term medication. Investigations revealed HO, which was suspected to envelop the median nerve in the proximal forearm. After several unsuccessful medication trials, the literature was reviewed in search of common variables between HO formation and persistent PLP. Ultimately, the biochemical effects associated with nerve injury were identified to be a possible factor in both HO and PLP development. Calcitonin's proposed mechanisms of action may help to manage HO and PLP at multiple stages of disease development and maintenance. In the present case, a four-week trial of intranasal calcitonin was successful, with pain control lasting at least 18 months., Conclusion: The present case report provided a review of the current literature in PLP pharmacological management and the current understanding of the etiology of PLP and HO, as well as how the two may coexist. It also provided an opportunity to discuss the proposed mechanisms of action of calcitonin in the management of PLP and HO.

To explore the effects of phantom phenomena on a group of dysvascular lower limb amputees. This was a cross-sectional study of dysvascular lower limb amputees. A modified version of the phantom phenomena questionnaire was used to measure the prevalence of phantom phenomena and the effects of those phenomena on daily life. Eighty-nine amputees were recruited. The majority were inpatients (72%) and male (72%). Most had pain before amputation (83%). Sixty-three percent had phantom limb pain. No associations were found between phantom limb pain and preamputation pain (p = .397). Phantom limb pain was present immediately on waking from amputation in 23%. Phantom limb pain is highly fluctuant. It is more likely that phantom limb pain was present with more time passed since amputation (p = .002). Outpatients with unhealed wounds were less likely to have phantom limb pain (p = .007). The effects of postamputation phenomena include sleep loss and social restrictions. These results challenge the belief that phantom limb pain reduces over time as more outpatients reported phantom limb pain than inpatients. Preamputation pain is not linked to the presence of phantom limb pain. The fluctuant nature of phantom limb pain makes its treatment complex. Some may wish intensity to reduce, whereas others may prefer to reduce the number of episodes or duration of each episode instead. More research is needed to clarify the needs of amputees in relation to the postamputation phenomena., (Copyright © 2015 American Society for Pain Management Nursing. Published by Elsevier Inc. All rights reserved.)

Congenital limb differences are uncommon birth defects that may go undetected even with prenatal screening ultrasound scans and often go undetected until birth. For children with congenital limb differences, a diagnostic evaluation should be done to rule out syndromes involving other organ systems or known associations. The most common etiology of acquired amputation is trauma. Postamputation complications include pain and terminal bony overgrowth. A multidisciplinary approach to management with the child and family can lead to a successful, functional, and fulfilling life., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Background: Post amputation pain presents a challenge for pain physicians and is often detrimental to the patient's quality of life., Patients and Methods: A prospective 12-week non-interventional study (NIS) was conducted in Germany to obtain data on the effectiveness and safety of capsaicin 8 % cutaneous patches from real life use in patients with peripheral neuropathic pain. For the first time in a subgroup of amputees data on post amputation pain were collected. This article presents the results for patients who suffered from phantom limb pain (PLP), stump pain (SP) and combined phantom limb/stump pain (PLP/SP)., Results: The analyses included 21 patients with post amputation pain (PLP: n = 10, SP: n = 4, PLP/SP: n = 7). The mean duration of pain (± standard deviation) was 12.8 ± 13.0 years for PLP, 23.1 ± 29.9 years for SP and 11.0 ± 15.8 years for PLP/SP. A single treatment with capsaicin 8 % cutaneous patches significantly reduced the average pain intensity over the observational period of 12 weeks. The mean numeric pain rating scale (NPRS) baseline score changed by - 2.4 for PLP with a standard error of the mean (SEM) of 0.4 (median: - 2.9, Q1: - 3.5, Q3: - 1.0), - 1.7 for SP (SEM: 0.8, median: - 1.1, Q1: - 2.9, Q3: - 0.5) and - 1.5 for PLP/SP (SEM: 0.6, median: - 2.0, Q1: - 2.3, Q3: 0) during weeks 1-12. The 30 % responder rates (i.e. ≥ 30 % reduction in pain, day 7/14 to week 12) were 70.0 % (PLP), 50.0 % (SP) and 28.6 % (PLP/SP). PLP and PLP/SP patients in particular, benefited from improvements in pain attacks, sleep duration and sleep quality and one patient (PLP/SP) reported an adverse drug reaction (increase of pain). Physicians rated the tolerability of the patch as very good or good in 90.5 % of patients. A poor tolerability was stated for none of the 21 amputees. Of the patients 80 % for PLP and 50 % for both SP and PLP/SP expressed the wish to receive retreatment with capsaicin 8 % patches., Conclusion: Capsaicin 8 % cutaneous patches seem to be effective and safe for the treatment of post amputation pain, notably in patients suffering from phantom limb pain.

Nearly all amputees continue to feel their missing limb as if it still existed, and many experience chronic phantom limb pain (PLP). What is the origin of these sensations? There is currently a broad consensus among investigators that PLP is a top-down phenomenon, triggered by loss of sensory input and caused by maladaptive cortical plasticity. We tested the alternative hypothesis that PLP is primarily a bottom-up process, due not to the loss of input but rather to exaggerated input, generated ectopically in axotomized primary afferent neurons in the dorsal root ganglia (DRGs) that used to innervate the limb. In 31 amputees, the local anesthetic lidocaine was applied intrathecally and/or to the DRG surface (intraforaminal epidural block). This rapidly and reversibly extinguished PLP and also nonpainful phantom limb sensation (npPLS). Control injections were ineffective. For intraforaminal block, the effect was topographically appropriate. The suppression of PLP and npPLS could also be demonstrated using dilute lidocaine concentrations that are sufficient to suppress DRG ectopia but not to block the propagation of impulses generated further distally in the nerve. PLP is driven primarily by activity generated within the DRG. We recommend the DRG as a target for treatment of PLP and perhaps also other types of regional neuropathic pain., (Copyright © 2014 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.)

Objective: Review the current evidence-based pharmacotherapy for phantom limb pain (PLP) in the context of the current understanding of the pathophysiology of this condition., Design: We conducted a systematic review of original research papers specifically investigating the pharmacologic treatment of PLP. Literature was sourced from PubMed, Embase, Scopus, and the Cochrane Central Register of Controlled Trials (CENTRAL). Studies with animals, "neuropathic" but not "phantom limb" pain, or without pain scores and/or functional measures as primary outcomes were excluded. A level of evidence 1-4 was ascribed to individual treatments. These levels included meta-analysis or systematic reviews (level 1), one or more well-powered randomized, controlled trials (level 2), retrospective studies, open-label trials, pilot studies (level 3), and anecdotes, case reports, or clinical experience (level 4)., Results: We found level 2 evidence for gabapentin, both oral (PO) and intravenous (IV) morphine, tramadol, intramuscular (IM) botulinum toxin, IV and epidural Ketamine, level 3 evidence for amitriptyline, dextromethorphan, topiramate, IV calcitonin, PO memantine, continuous perineural catheter analgesia with ropivacaine, and level 4 evidence for methadone, intrathecal (IT) buprenorphine, IT and epidural fentanyl, duloxetine, fluoxetine, mirtazapine, clonazepam, milnacipran, capsaicin, and pregabalin., Conclusions: Currently, the best evidence (level 2) exists for the use of IV ketamine and IV morphine for the short-term perioperative treatment of PLP and PO morphine for an intermediate to long-term treatment effect (8 weeks to 1 year). Level 2 evidence is mixed for the efficacy of perioperative epidural anesthesia with morphine and bupivacaine for short to long-term pain relief (perioperatively up to 1 year) as well as for the use of gabapentin for pain relief of intermediate duration (6 weeks)., (Wiley Periodicals, Inc.)

The purpose of this literature review was to describe the main features of phantom eye syndrome in relation to their possible causes, symptoms, treatments, and influence of eye amputation on quality of life of anophthalmic patients. For this, a bibliographical research was performed in Pubmed database using the following terms: "eye amputation," "eye trauma," "phantom eye syndrome," "phantom pain," and "quality of life," associated or not. Thirteen studies were selected, besides some relevant references contained in the selected manuscripts and other studies hallowed in the literature. Thus, 56 articles were included in this review. The phantom eye syndrome is defined as any sensation reported by the patient with anophthalmia, originated anophthalmic cavity. In phantom eye syndrome, at least one of these three symptoms has to be present: phantom vision, phantom pain, and phantom sensations. This syndrome has a direct influence on the quality of life of the patients, and psychological support is recommended before and after the amputation of the eyeball as well as aid in the treatment of the syndrome. Therefore, it is suggested that, for more effective treatment of phantom eye syndrome, drug therapy should be associated with psychological approach.

Introduction: Managing neuropathic pain can be very challenging, with standard medical therapies often providing inadequate relief. It has recently been reported in the literature that statins alleviate neuropathic pain in the rat model. We present a case report in which an above-the-knee amputee achieved relief of his neuropathic stump pain with atorvastatin., Case Report: We describe the case of a 50-year-old man with a 12-year history of chronic neuropathic stump pain and sporadic phantom limb pain following an above-the-knee amputation. For 11 years the pain was managed with gabapentin 300 mg 3 times daily plus oxycodone 10 mg twice daily. He autonomously weaned himself to gabapentin 300 mg once daily and oxycodone 10 mg once daily, exacerbating his stump pain in the process. After starting atorvastatin 20 mg once daily for hypercholesterolemia, he immediately experienced decreased intensity of his stump pain, but his phantom pain persisted at its usual intensity., Conclusions: More studies are needed to characterize the analgesic effects of statins better. In patients who have neuropathic pain refractory to traditional treatment options or, rather, decline traditional treatment options, statin therapy may be helpful.

Phantom limb pain is a common consequence of limb amputation and is prevalent among the service members sustaining traumatic battlefield limb injuries during the conflicts in Iraq and Afghanistan. Current treatment to relieve phantom limb pain consists of physical, behavioral, and medical modalities including opioids and adjunct medications. Treatment failure resulting in persistent pain and disability may result. This case series describes four previously healthy service members who developed phantom limb pain following traumatic amputation successfully treated with buprenorphine/naloxone after failing traditional treatment. This is the first reported case series of patients expressing improved pain control with decreased frequency of phantom limb pain with the use of buprenorphine/naloxone instead of traditional opioid agonists., (Reprint & Copyright © 2013 Association of Military Surgeons of the U.S.)

Background: There is currently no reliable treatment for phantom limb pain (PLP). Chronic PLP and associated cortical abnormalities may be maintained from abnormal peripheral input, raising the possibility that a continuous peripheral nerve block (CPNB) of extended duration may permanently reorganize cortical pain mapping, thus providing lasting relief., Methods: Three men with below-the-knee (2) or -elbow (1) amputations and intractable PLP received femoral/sciatic or infraclavicular perineural catheter(s), respectively. Subjects were randomized in a double-masked fashion to receive perineural ropivacaine (0.5%) or normal saline for over 6 days as outpatients using portable electronic infusion pumps. Four months later, subjects returned for repeated perineural catheter insertion and received an ambulatory infusion with the alternate solution ("crossover"). Subjects were followed for up to 1 year., Results: By chance, all three subjects received saline during their initial infusion and reported little change in their PLP. One subject did not receive crossover treatment, but the remaining two subjects reported complete resolution of their PLP during and immediately following treatment with ropivacaine. One subject experienced no PLP recurrence through the 52-week follow-up period and the other reported mild PLP occurring once each week of just a small fraction of his original pain (pretreatment: continuous PLP rated 10/10; posttreatment: no PLP at baseline with average of one PLP episode each week rated 2/10) for 12 weeks (lost to follow-up thereafter)., Conclusions: A prolonged ambulatory CPNB may be a reliable treatment for intractable PLP. The results of this pilot study suggest that a large, randomized clinical trial is warranted., (Wiley Periodicals, Inc.)

Atypical odontalgia (AO) is a little known chronic pain condition. It usually presents as pain in a site where a tooth was endodontically treated or extracted, in the absence of clinical or radiographic evidence of tooth pathology. It is a rare clinical challenge for most clinicians, which leads to the patients being referred to several specialists and sometimes undergoing unnecessary surgical procedures. The pain mechanisms involved in AO are far from clear, and numerous potential mechanisms have been suggested. Currently, the most accredited hypothesis is that AO is a neuropathic pain condition caused by deafferentation. The differential diagnosis of AO remains difficult, because it shares symptoms with many others pathologies affecting this area. Patients have difficulties accepting the AO diagnosis and treatment. As a result, they frequently change physicians, and may potentially also receive several invasive treatments, usually resulting in an aggravation of the pain. Although some patients do get complete pain relief following treatment, for most patients the goal should be to achieve adequate pain management. Currently, most management is based on expert opinion and case reports. More research and high quality randomized controlled trials are needed in order to develop evidence-based treatments, currently based on expert opinion or carried over from other neuropathic pain conditions in the orofacial region.

Background: Post-amputation pain is a multifactorial issue and thus necessitates multiple treatment strategies. Myofascial trigger points-related pain remains under diagnosed and hence not addressed. This study investigates causation and management., Objectives: To identify the presence and role of myofascial trigger points in post amputation pain., Study Design: Post-amputation pain clinic review and recruitment., Methods: Twenty one identified patients in the post-amputation pain clinic with myofascial trigger points were recruited, of which 13 were transtibial and eight transfemoral and all had phantom limb pain and stump pain. The trigger points were identified and injected with long-acting local anaesthetic on a weekly basis and patients were followed up on an ongoing basis., Results: There was significant resolution of pain on the Visual Analogue Scale in the majority of these patients within five weeks, though some of the transtibial cohort needed further eight injections on a weekly basis for resolution of the pain., Conclusion: Identification of myofascial trigger points in amputation stumps and their role in post-amputation pain, followed by appropriate intervention is an important facet of management of this complex chronic pain. Clinical relevance Myofascial trigger points in amputation stumps can lead to ongoing chronic post-amputation pain and our results indicate that identification and intervention of these trigger points does lead to notable resolution of this pain.

Objectives: The successful therapy of phantom pain remains a major challenge, because the underlying pathophysiological mechanisms are still not fully understood. A therapeutic approach with tapentadol has not been described so far., Patients and Methods: Five patients suffering upper and lower extremity phantom pain were successfully treated with tapentadol (prolonged release) with differing doses., Results: In 4 patients, a strongly reduced pain intensity between 4 and 6.5 on the visual analog scale (VAS) was recorded. The fifth patient reported an increase in the nocturnal sleep duration from 2 to 5 h and a decrease in the number of phantom pain attacks by 30 %. In 2 patients, the additional medication could be lowered or stretched. Side effects (vertigo, fatigue) were only observed in one subject., Conclusion: The cases described provide preliminary evidence that the synergistic combination of μ-opioid receptor agonism (MOR) and noradrenalin re-uptake inhibition (NRI) provided by tapentadol may be beneficial in the treatment of phantom pain.