Patient-centered results from a multicenter study of continuous peripheral nerve blocks and postamputation phantom and residual limb pain: secondary outcomes from a randomized, clinical trial.

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.

[Involuntary movements of the stump after transtibial amputation: Jumping stump syndrome]. / Movimientos involuntarios del muñón tras una amputación transtibial: síndrome del muñón saltarín.

45-year-old woman with history of hallux valgus surgery and torpid evolution, which led to transtibial amputation. Six months after surgery, she began to experience involuntary movements of the stump such as myoclonus, that were triggered by touch or hip extension, associating worsening of the previous stump and phantom limb pain. During the following year, concurring with change of prosthesis, symptoms progressively worsened, which limited walking. The therapeutic approach to pain and myoclonus was initially pharmacological, without response. Given the clinical and ultrasound suspicion of neuroma in the external popliteal sciatic nerve, it was infiltrated with corticosteroid and anesthetic, and the gastrocnemius with botulinum toxin type A, without success. Finally, the myoclonus disappeared, and the pain decreased after surgical remodeling of the stump and resection of the neuroma. This clinical picture is known as jumping stump syndrome and is a rare complication that must be considered after amputation.

Brain (re)organisation following amputation: Implications for phantom limb pain.

Following arm amputation the region that represented the missing hand in primary somatosensory cortex (S1) becomes deprived of its primary input, resulting in changed boundaries of the S1 body map. This remapping process has been termed 'reorganisation' and has been attributed to multiple mechanisms, including increased expression of previously masked inputs. In a maladaptive plasticity model, such reorganisation has been associated with phantom limb pain (PLP). Brain activity associated with phantom hand movements is also correlated with PLP, suggesting that preserved limb functional representation may serve as a complementary process. Here we review some of the most recent evidence for the potential drivers and consequences of brain (re)organisation following amputation, based on human neuroimaging. We emphasise other perceptual and behavioural factors consequential to arm amputation, such as non-painful phantom sensations, perceived limb ownership, intact hand compensatory behaviour or prosthesis use, which have also been related to both cortical changes and PLP. We also discuss new findings based on interventions designed to alter the brain representation of the phantom limb, including augmented/virtual reality applications and brain computer interfaces. These studies point to a close interaction of sensory changes and alterations in brain regions involved in body representation, pain processing and motor control. Finally, we review recent evidence based on methodological advances such as high field neuroimaging and multivariate techniques that provide new opportunities to interrogate somatosensory representations in the missing hand cortical territory. Collectively, this research highlights the need to consider potential contributions of additional brain mechanisms, beyond S1 remapping, and the dynamic interplay of contextual factors with brain changes for understanding and alleviating PLP.

Selective nerve root injection of ozone for the treatment of phantom limb pain: Three case reports.

RATIONALE: Phantom limb pain (PLP) refers to a common complication following amputation, which is characterized by intractable pain in the absent limb, phantom limb sensation, and stump pain. The definitive pathogenesis of PLP has not been fully understood, and the treatment of PLP is still a great challenge. Till now, ozone injection has never been reported for the treatment of PLP. PATIENT CONCERNS: We report 3 cases: a 68-year-old man, a 48-year-old woman, and a 46-year-old man. All of them had an amputation history and presented with stump pain, phantom limb sensation, and sharp pain in the phantom limb. Oral analgesics and local blocking in stump provided no benefits. DIAGNOSIS: They were diagnosed with PLP. INTERVENTIONS: We performed selective nerve root ozone injection combined with ozone injection in the stump tenderness points. OUTCOMES: There were no adverse effects. Postoperative, PLP, and stump pain were significantly improved. During the follow-up period, the pain was well controlled. LESSONS: Selective nerve root injection of ozone is safe and the outcomes were favorable. Ozone injection may be a new promising approach for treating PLP.

Arthur Rimbaud: "The Man with Wind Soles" - Riders' Osteosarcoma with Postamputation Stump Pain.

The famous poet Arthur Rimbaud (1854-1891) stopped writing poetry at 21 years and subsequently had a rather adventurous life mainly in the Arabic peninsula and Ethiopia. He died at 37 years, only a few months after the amputation of his right lower limb due to a developing tumor in the knee, which probably was an osteosarcoma in the lower third of the femur. His letters to his sister Isabelle suggest that he suffered from severe stump pain rather than phantom limb, but since he lived only shortly after surgery (he developed extensive carcinomatosis), one does not know whether a full phantom would have developed and how this would have affected his subsequent life.

Relieving phantom limb pain with multimodal sensory-motor training.

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

Patient care for postamputation pain and the complexity of therapies: living experiences.

AIM: Limb amputation traumatically alters body image. Sensations rapidly prevail that the limb is still present and 85% of patients portray phantom limb pain. Throughout the testimonies of amputated patients with intense phantom limb pain, we show the difficulty in treating this chronic pain with current pharmacological and nonpharmacological therapies. PATIENTS & METHODS: We qualitatively analyzed the therapeutic choices of five amputees, the effectiveness of the treatments chosen and the impact on patients' quality-of-life. RESULTS & CONCLUSION: In general, patients who are refractory to pharmacological treatments are in favor of trying alternative therapies. It is therefore crucial to design a combined and personalized therapeutic plan under the coordination of a multidisciplinary team for the wellbeing of the patient.

Cortical plasticity as a basis of phantom limb pain: Fact or fiction?

Cortical reorganization has been proposed as a major factor involved in phantom pain with prior nociceptive input to the deafferented region and input from the non-deafferented cortex creating neuronal activity that is perceived as phantom pain. There is substantial evidence that these processes play a role in neuropathic pain, although causal evidence is lacking. Recently it has been suggested that a maintenance of the cortical representation of the former hand area is related to phantom pain. Although interesting, evidence for this process is so far scarce. In addition, peripheral factors have been proposed as important for phantom limb pain. Although often introduced as contradictory, we suggest that cortical reorganization, preserved limb function and peripheral factors interact to create the various painful and nonpainful aspects of the phantom limb experience. In addition, the type of task (sensory versus motor), the interaction of injury- and use-dependent plasticity, the type of data analysis, contextual factors such as the body representation and psychological variables determine the outcome and need to be considered in models of phantom limb pain. Longitudinal studies are needed to determine the formation of the phantom pain experience.

Chronic pain and other symptoms among breast cancer survivors: prevalence, predictors, and effects on quality of life.

PURPOSE: To investigate prevalence and risk factors associated with self-reported chronic pain, and other symptoms related to breast cancer or its treatment among breast cancer survivors (BCS). METHODS: A cross-sectional study of a random sample of 410 female BCS, members of "Leumit" healthcare fund, diagnosed with primary nonmetastatic invasive breast cancer in the years 2002-2012. The study questionnaire included questions on health-related quality of life, pain symptoms, and was completed by all women contacted. RESULTS: A total of 305 BCS (74%), with a median of 7.4 years since diagnosis reported chronic pain, of whom 84% had moderate pain, and 97% experienced pain at least 1-3 days/week. Other symptoms were paresthesia (63%), allodynia (48%), and phantom sensations (15%). Report of pain symptoms, alone or combined, was significantly associated with poorer quality of life. In multivariable analyses, chronic pain was positively associated with mastectomy compared to breast-conserving surgery [Odds ratio (OR), 3.54; 95% confidence interval (CI) 1.46-8.59; P = 0.005], radiotherapy compared to non-radiotherapy (OR 2.96; 95% CI 1.43-6.12; P = 0.003), breast cancer stage at diagnosis-regional versus localized (OR 3.63; 95% CI 2.00-6.57; P < 0.001), and inversely with age (OR per one-year increment, 0.96; 95% CI 0.94-0.99; P = 0.002), and with time since diagnosis (OR per one-year increment, 0.82; 95% CI 0.75-0.90; P < 0.001). CONCLUSIONS: With the increasing incidence of detected breast cancer and the improvements in treatment and consequently survival, knowledge about prevalence, and factors related to treatment late effects of chronic pain is highly relevant for potential prevention or management without negatively impacting quality of life.

Repetitive Transcranial Magnetic Stimulation for Phantom Limb Pain in Land Mine Victims: A Double-Blinded, Randomized, Sham-Controlled Trial.

UNLABELLED: We evaluated the effects of repetitive transcranial magnetic stimulation (rTMS) in the treatment of phantom limb pain (PLP) in land mine victims. Fifty-four patients with PLP were enrolled in a randomized, double-blinded, placebo-controlled, parallel group single-center trial. The intervention consisted of real or sham rTMS of M1 contralateral to the amputated leg. rTMS was given in series of 20 trains of 6-second duration (54-second intertrain, intensity 90% of motor threshold) at a stimulation rate of 10 Hz (1,200 pulses), 20 minutes per day, during 10 days. For the control group, a sham coil was used. The administration of active rTMS induced a significantly greater reduction in pain intensity (visual analogue scale scores) 15 days after treatment compared with sham stimulation (-53.38 ± 53.12% vs -22.93 ± 57.16%; mean between-group difference = 30.44%, 95% confidence interval, .30-60.58; P = .03). This effect was not significant 30 days after treatment. In addition, 19 subjects (70.3%) attained a clinically significant pain reduction (>30%) in the active group compared with 11 in the sham group (40.7%) 15 days after treatment (P = .03). The administration of 10 Hz rTMS on the contralateral primary motor cortex for 2 weeks in traumatic amputees with PLP induced significant clinical improvement in pain. PERSPECTIVE: High-frequency rTMS on the contralateral primary motor cortex of traumatic amputees induced a clinically significant pain reduction up to 15 days after treatment without any major secondary effect. These results indicate that rTMS is a safe and effective therapy in patients with PLP caused by land mine explosions.

Spinal Cord Stimulation Therapy for the Treatment of Concomitant Phantom Limb Pain and Critical Limb Ischemia.

Phantom limb pain (PLP) is a chronic condition experienced by about 80% of patients who have undergone amputation. In most patients, both the frequency and the intensity of pain attacks diminish with time, but severe pain persists in about 5-10%. Probably, factors in both the peripheral and central nervous system play a role in the occurrence and persistence of pain in the amputated lower limb. The classical treatment of PLP can be divided into pharmacologic, surgical, anesthetic, and psychological modalities. Spinal cord stimulation (SCS) does not represent a new method of treatment for this condition. However, the concomitant treatment of PLP and critical lower limb ischemia by using SCS therapy has not yet been described in the current literature. The aim of the present article is to highlight the possibility of apply SCS for the simultaneous treatment of PLP and critical lower limb ischemia on the contralateral lower limb after failure of medical therapy in a group of 3 patients, obtaining pain relief in both lower limbs, delaying an endovascular or surgical revascularization. After SCS implantation and test stimulation, the pain was reduced by 50% on both the right and the left side in all our patients. The main indications for permanent SCS therapy after 1 week of test stimulation were represented by transcutaneous oxygen (TcPO2) increase >75%, decrease of opioids analgesics use of at least 50% and a pain maintained to within 20-30/100 mm on visual analog scale.

Use of calcitonin in recalcitrant phantom limb pain complicated by heterotopic ossification.

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.

The relationship between prosthesis use, phantom pain and psychiatric symptoms in male traumatic limb amputees.

OBJECTIVES: The purpose of this study was to identify psychiatric symptoms by comparing male patients with traumatic leg amputations (LAs) with healthy controls and to determine the association between these psychiatric symptoms and phantom pain and prosthesis use characteristics. METHODS: One hundred four volunteers, 51 LA patients (group 1) and 53 healthy controls (group 2) were included. Demographic data including age, height, weight, time since amputation, duration of prosthesis use, and Satisfaction with Prosthesis Questionnaire scores were recorded. Phantom pain was measured a visual analog scale (VAS). Psychiatric symptoms were measured using the Symptom Checklist-90-R, Beck Depression Inventory, Pittsburgh Sleep Quality Index, Rosenberg Self-Esteem Scale, and State-Trait Anxiety Inventory. Correlations were determined between time since amputation, duration of prosthesis use and satisfaction with prosthesis questionnaire scores and psychiatric scale scores. RESULTS: Amputee patients had higher phobic anxiety, state anxiety, trait anxiety and sleep disturbance scores (p<0.05) than the controls. No difference was determined in terms of psychiatric symptoms between the phantom pain and no phantom pain groups (p>0.05). There were significant negative correlations between time since amputation, duration of prosthesis use, duration of daily prosthesis use, and satisfaction with prosthesis questionnaire scores and psychiatric symptoms. CONCLUSIONS: Apart from anxiety (state, trait or phobic) and disturbed sleep, other psychiatric symptoms in amputee patients undergoing lengthy prosthetic rehabilitation may not differ from those of healthy controls. The presence and severity of phantom pain appear to be unrelated to general psychiatric symptomatology. Length of time since amputation, length of prosthesis use, daily length of prosthesis use and prosthesis satisfaction are negatively correlated with general psychiatric symptoms. These characteristics must be borne in mind in psychiatric and prosthetic rehabilitation.

Heightened motor and sensory (mirror-touch) referral induced by nerve block or topical anesthetic.

Mirror neurons allow us to covertly simulate the sensation and movement of others. If mirror neurons are sensory and motor neurons, why do we not actually feel this simulation- like "mirror-touch synesthetes"? Might afferent sensation normally inhibit mirror representations from reaching consciousness? We and others have reported heightened sensory referral to phantom limbs and temporarily anesthetized arms. These patients, however, had experienced illness or injury of the deafferented limb. In the current study we observe heightened sensory and motor referral to the face after unilateral nerve block for routine dental procedures. We also obtain double-blind, quantitative evidence of heightened sensory referral in healthy participants completing a mirror-touch confusion task after topical anesthetic cream is applied. We suggest that sensory and motor feedback exist in dynamic equilibrium with mirror representations; as feedback is reduced, the brain draws more upon visual information to determine- perhaps in a Bayesian manner- what to feel.

Radicular pain from lumbar canal stenosis in addition to pre-existing phantom limb pain.

Phantom limb (PL) is a term used to designate the sensation of the presence of an extremity following amputation, and it may be seen immediately after injury or years later in the part of the body that is deafferented or amputated. Phantom limb pain (PLP) is the term used to describe painful sensations referred to the absent limb. We present a case of a 71-year-old male with spinal claudication from discoligamentous lumbar canal stenosis L3-L4 and L4-L5 with L5 radicular pain in the left PL 13 years after the amputation. The patient had a disappearance of his radicular pain in the left PL following microsurgical lumbar decompression of L3-L4 and L4-L5. This is one of the rare cases reported in the literature in which a radicular pain in the PL disappeared following surgical decompression of the spinal canal.

[Burning sensation in oral cavity--burning mouth syndrome in everyday medical practice]. / Égo érzés a szájüregben--a "burning mouth" szindróma a mindennapos orvosi gyakorlatban.

Burning mouth syndrome (BMS) refers to chronic orofacial pain, unaccompanied by mucosal lesions or other evident clinical signs. It is observed principally in middle-aged patients and postmenopausal women. BMS is characterized by an intense burning or stinging sensation, typically on the tongue or in other areas of the oral mucosa. It can be accompanied by other sensory disorders such as dry mouth or taste alterations. Probably of multifactorial origin, and often idiopathic, with a still unknown etiopathogenesis in which local, systemic and psychological factors are implicated. Currently there is no consensus on the diagnosis and classification of BMS. This study reviews the literature on this syndrome, with special reference to the etiological factors that may be involved and the clinical aspects they present. The diagnostic criteria that should be followed and the therapeutic management are discussed with reference to the most recent studies.

The contribution of sympathetic mechanisms to postamputation phantom and residual limb pain: a pilot study.

UNLABELLED: Postamputation pain (PAP) affects over 60% of major limb amputees. One of the main challenges in treating PAP is the difficulty involved in identifying pain mechanism(s), which pertains to both residual limb pain (RLP) and phantom limb pain (PLP). In this study, sympathetic blocks were performed on 17 major limb amputees refractory to treatment, including 2 placebo-controlled blocks done for bilateral amputations. One hour postinjection, mean RLP scores at rest declined from 5.2 (SD 2.8) to 2.8 (SD 2.6) (P = .0002), and PLP decreased from 5.3 (SD 3.1) to 2.3 (SD 2.1) (P = .0009). By 1 week, mean pain scores for RLP and PLP were 4.3 (SD 2.9) and 4.2 (SD 3.0), respectively. Overall, 8 of 16 (50%) patients experienced ≥50% reduction in RLP 1-hour postinjection, with the beneficial effects being maintained at 1 and 8 weeks in 4 and 1 patient(s), respectively. For PLP, 8 of 15 (53%) patients obtained ≥50% decrease in pain 1-hour postblock, with these numbers decreasing to 2 patients at both 1 and 8 weeks. In the 2 bilateral amputees who received controlled injections, mean PLP and RLP at rest scores went from 4.0 and 3.3 to 4.0 and 2.5 1-hour postblock, respectively, on the placebo side. On the treatment side, mean PLP and RLP scores decreased from 7.5 and 6.5, respectively, to 0. PERSPECTIVE: The results of this study suggest that sympathetic mechanisms play a role in PLP and to a lesser extent, RLP, but that blocks confer long-term benefits in only a small percentage of patients.

21. Phantom pain.

Phantom pain is pain caused by elimination or interruption of sensory nerve impulses by destroying or injuring the sensory nerve fibers after amputation or deafferentation. The reported incidence of phantom limb pain after trauma, injury or peripheral vascular diseases is 60% to 80%. Over half the patients with phantom pain have stump pain as well. Phantom pain can also occur in other parts of the body; it has been described after mastectomies and enucleation of the eye. Most patients with phantom pain have intermittent pain, with intervals that range from 1 day to several weeks. Even intervals of over a year have been reported. The pain often presents itself in the form of attacks that vary in duration from a few seconds to minutes or hours. In most cases, the pain is experienced distally in the missing limb, in places with the most extensive innervation density and cortical representation. Although there are still many questions as to the underlying mechanisms, peripheral as well as central neuronal mechanisms seem to be involved. Conservative therapy consists of drug treatment with amitriptyline, tramadol, carbamazepine, ketamine, or morphine. Based on the available evidence some effect may be expected from drug treatment. When conservative treatment fails, pulsed radiofrequency treatment of the stump neuroma or of the spinal ganglion (DRG) or spinal cord stimulation could be considered (evidence score 0). These treatments should only be applied in a study design.

Robotic microsurgery 2011: male infertility, chronic testicular pain, postvasectomy pain, sports hernia pain and phantom pain.

PURPOSE OF REVIEW: The use of robotic assistance during microsurgical procedures has evolved from its early beginnings in the early 2000s. Currently, its use is expanding in the treatment of male infertility and patients with chronic testicular or groin pain. The addition of this technology may allow an improvement in outcomes as when the operating microscope was introduced in microsurgery. However, this is yet to be proven. RECENT FINDINGS: This review covers new robotic microsurgical tools and applications of the robotic platform in microsurgical procedures such as vasectomy reversal, varicocelectomy, microsurgical denervation of the spermatic cord for chronic testicular or groin pain, post-vasectomy pain, sports hernia pain, postnephrectomy, donor nephrectomy and phantom groin pain. Preliminary animal studies show an advantage in terms of improved operative efficiency and improved surgical outcomes. Preliminary human clinical studies appear to support these findings. The use of robotic assistance during robotic microsurgical vasovasostomy appears to decrease operative duration and improve early postoperative sperm counts compared to the pure microsurgical technique. SUMMARY: Long-term prospective controlled trials are necessary to assess the true cost-benefit ratio for robotic assisted microsurgery. The preliminary findings are promising and evidence is mounting, but further evaluation is warranted.