Epidemiology and risk factors for phantom limb pain.

Approximately 356 million limb amputations are performed globally every year. In 2005, the prevalence of limb loss in the United States was 1.6 million people; and it is estimated to increase to 3.6 million by 2050. Many post-amputation patients experience chronically altered sensations and pain associated with the amputation, such as phantom limb pain. The risk factors for phantom limb pain are widely debated in the literature due to the heterogeneity of the population being studied. This review will highlight both the non-operative and operative risk factors for phantom limb pain.

Robotic-Enhanced Prosthetic Liners for Vibration Therapy: Reducing Phantom Limb Pain in Transfemoral Amputees.

Phantom limb pain, a common challenge for amputees, lacks effective treatment options. Vibration therapy is a promising non-pharmacologic intervention for reducing pain intensity, but its efficacy in alleviating phantom limb pain requires further investigation. This study focused on developing prosthesis liners with integrated vibration motors to administer vibration therapy for phantom limb pain. The prototypes developed for this study addressed previous issues with wiring the electronic components. Two transfemoral amputees participated in a four-week at-home trial, during which they used the vibration liner and rated their initial and final pain intensity on a numeric rating scale each time they had phantom pain. Semi-structured interviews were conducted to gather feedback following the at-home trial. Both participants described relaxing and soothing sensations in their residual limb and phantom limb while using vibration therapy. One participant reported a relaxation of his phantom limb sensations, while both participants noted a decrease in the intensity of their phantom limb pain. Participants said the vibration liners were comfortable but suggested that the vibration could be stronger and that aligning the contacts could be easier. The results of this study highlight the potential effectiveness of using vibration therapy to reduce the intensity of phantom limb pain and suggest a vibration liner may be a feasible mode of administering the therapy. Future research should address optimizing the performance of the vibration liners to maximize their therapeutic benefits.

Current and Future Directions for Upper Extremity Amputations: Comparisons Between Regenerative Peripheral Nerve Interface and Targeted Muscle Reinnervation Surgeries.

Upper extremity amputation can lead to significant functional morbidity. The main goals after amputation are to minimize pain and maintain or improve functional status while optimizing the quality of life. Postamputation pain is common and can be addressed with regenerative peripheral nerve interface surgery or targeted muscle reinnervation surgery. Both modalities are effective in treating residual limb pain and phantom limb pain, as well as improving prosthetic use. Differences in surgical technique between the 2 approaches need to be weighed when deciding what strategy may be most appropriate for the patient.

Analysis of Natural Antibodies during the Development of Phantom Pain Syndrome.

We determined natural antibodies (n-Abs) to the regulators of the main systems of biochemical homeostasis: ß-endorphin, serotonin, dopamine, histamine, orphanin, angiotensin, GABA, glutamate, bradykinin, vasopressin, thrombin, and α-2-macroglobulin in individuals with phantom pain syndrome (PPS), resulting from amputation after injury. It was established that each patient has an individual immunoprofile, but for all of them there was a significant increase in the level of antibodies to serotonin, histamine, and angiotensin, which reflect the chronicity of the pain syndrome and do not depend on the self-assessment of the severity of PPS. Determination of the role of regulators of biochemical homeostasis in the development of phantom pain showed that, at high, moderate, and weak severity of PPS, the biogenic amine and angiotensinergic systems are activated. A decrease in PPS intensity normalizes deviations in all immunological parameters. The levels of n-Abs for the pain (ß-endorphin) and analgesic (orphanin) systems are significant only at low PPS. Monitoring the individual profile of n-Abs to endogenous regulators allows us to obtain an objective picture of the pain status of the patient's body.

Dorsal Root Ganglion Stimulation for the Management of Phantom Bladder Pain: A Case Report.

Phantom bladder pain, a rare condition following cystectomy, can pose a challenge to pain management providers. We present the case of a 43-year-old male who developed severe phantom bladder pain post-cystectomy. Despite multiple treatments, his symptoms persisted, significantly affecting his quality of life. Dorsal root ganglion stimulation (DRGS) was attempted after conventional therapies failed. The DRGS trial provided significant relief, leading to permanent implantation and a 90% reduction in pain. This case highlights DRGS as a potential treatment for phantom bladder pain, expanding its applications beyond traditional uses. Further research is needed to elucidate its mechanisms and broader applicability.

[Treatment and prevention phantom pain syndrome in mine-explosive injuries]. / Analiz ispol'zovaniya sovremennykh metodov lecheniya i profilaktiki fantomnogo bolevogo sindroma pri minno-vzryvnykh travmakh.

Phantom pain syndrome significantly impairs the quality of life and effectiveness of surgical treatment after limb amputations. The authors consider possible strategies for treatment and prevention in elective surgical intervention and mine-explosive injuries.

Lower jaw-to-forepaw rapid and delayed reorganization in the rat forepaw barrel subfield in primary somatosensory cortex.

We used the forepaw barrel subfield (FBS), that normally receives input from the forepaw skin surface, in rat primary somatosensory cortex as a model system to study rapid and delayed lower jaw-to-forepaw cortical reorganization. Single and multi-unit recording from FBS neurons was used to examine the FBS for the presence of "new" lower jaw input following deafferentations that include forelimb amputation, brachial plexus nerve cut, and brachial plexus anesthesia. The major findings are as follows: (1) immediately following forelimb deafferentations, new input from the lower jaw becomes expressed in the anterior FBS; (2) 7-27 weeks after forelimb amputation, new input from the lower jaw is expressed in both anterior and posterior FBS; (3) evoked response latencies recorded in the deafferented FBS following electrical stimulation of the lower jaw skin surface are significantly longer in both rapid and delayed deafferents compared to control latencies for input from the forepaw to reach the FBS or for input from lower jaw to reach the LJBSF; (4) the longer latencies suggest that an additional relay site is imposed along the somatosensory pathway for lower jaw input to access the deafferented FBS. We conclude that different sources of input and different mechanisms underlie rapid and delayed reorganization in the FBS and suggest that these findings are relevant, as an initial step, for developing a rodent animal model to investigate phantom limb phenomena.

A case of phantom pain and stump pain that was effectively controlled by ultrasound-guided ulnar and median peripheral nerve blocks.

Phantom limb pain and stump pain are often intractable, and their incidences are relatively high. We report a case of a patient with phantom limb and stump pain of the finger, who was successfully treated by peripheral nerve blocks. The patient was a male truck driver in his fifties, who had his left annular finger amputated in an accident 2 years previously. Owing to poor pain control at the stump of his finger, he was referred to our department. The initial examination revealed pain about numerical rating scale (NRS) 6/10 in the left annular finger transection as well as allodynia. Although some pain relief had been observed with postoperative medication, he still had persistent resting pain of about NRS 4/10. Therefore, blocks of the ulnar nerve and median nerve were performed. After the blocks were performed, the pain improved to NRS 1 to 2/10, and pain upon movement also almost disappeared. Peripheral nerve blocks can be a useful treatment modality for phantom limb pain and stump pain in the fingers, as in this case.

Dolor de miembro fantasma una complicación frecuente en el paciente amputado / Phantom pain, a frequent complication in amputee patients

Introducción: La amputación de la extremidad con frecuencia da lugar a alteraciones sensoriales, dolorosas o no, tales como el síndrome del miembro fantasma, que dificulta el proceso de rehabilitación y afecta el estado psicológico del paciente. El dolor de miembro fantasma ha sido descrito como una condición en la que los pacientes experimentan una sensación dolorosa en el miembro ausente. Objetivo: Describir aspectos esenciales del dolor fantasma como complicación en los pacientes amputados Métodos: Se realizó una búsqueda de la literatura publicada durante el período comprendido entre enero de 2015 y diciembre de 2021 que hiciera referencia al dolor en miembro fantasma en paciente amputado. Resultados: Entre las causas que conllevan a la amputación de una extremidad se encuentran los problemas vasculares, trauma, cáncer y alteraciones congénitas, es importante tenerlas en consideración debido a los efectos psicológicos y socioeconómicos que puede tener en el paciente. El síndrome del miembro fantasma se divide en miembro o sensación fantasma, dolor de miembro fantasma y muñón doloroso. Es importante hacer distinciones entre ellos, lo que ayuda a evaluar la magnitud del problema y el tratamiento que es diferente. El tratamiento convencional no ha sido muy efectivo. Conclusiones: Se describieron los aspectos esenciales del dolor fantasma como complicación en los pacientes amputados, el manejo y tratamiento del dolor de miembro fantasma en miembros amputados, constituye una prioridad a vencer dentro de las pautas de la medicina moderna(AU)

Introduction: Limb amputation often gives rise to sensory alterations, painful or not, such as phantom limb syndrome, which hinders the rehabilitation process and affects the patient's psychological state. Phantom limb pain has been described as a condition in which patients experience a painful sensation in the missing limb. Objective: To describe essential aspects of phantom pain as a complication in amputee patients. Methods: A search of the literature published between January 2015 and December 2021 that referred to phantom limb pain in amputee patients was carried out. Results: Among the causes that lead to the amputation of a limb are vascular problems, trauma, cancer and congenital alterations, it is important to take them into consideration due to the psychological and socioeconomic effects that they can have on the patient. Phantom limb syndrome is divided into phantom limb or sensation, phantom limb pain, and painful stump. It is important to make distinctions between them, which helps to assess the magnitude of the problem and the treatment that is different. Conventional treatment has not been very effective. Conclusions: The management and treatment of phantom limb pain in amputated limbs is a priority to be overcome within the guidelines of modern medicine, which is why care intervention is necessary in order to improve the quality of life of the amputated patient and their better rehabilitation(AU)

An Algorithm Approach to Phantom Limb Pain.

Phantom limb pain (PLP) is a common condition that occurs following both upper and lower limb amputation. First recognized and described in 1551 by Ambroise Pare, research into its underlying pathology and effective treatments remains a very active and growing field. To date, however, there is little consensus regarding the optimal management of phantom limb pain. With few large well-designed clinical trials of which to make treatment recommendations, as well as significant heterogeneity in clinical response to available treatments, the management of PLP remains challenging. Below we summarize the current state of knowledge in the field, as well as propose an algorithm for the approach to the treatment of PLP.

A Rare Occurrence of Phantom Tongue Pain.

This is a case of phantom tongue pain observed in a 65-year-old male with a history of adenoid cystic carcinoma with involvement of the base of the tongue and supraglottic laryngopharyngeal cancer who underwent a laryngopharyngectomy and glossectomy for treatment. The patient subsequently developed phantom tongue pain in acute rehabilitation. Post total glossectomy phantom pain is rare, and as this is a singular appendage, current techniques that rely on the presence of an intact limb, such as mirror therapy could not be applied to our patient. Therefore mental imagery techniques originally developed for extremity amputation required adaptation to the context of total glossectomy. Recommended anticonvulsant medications, desensitization, and mental imagery techniques for phantom limb pain were effective in relieving the patient's phantom tongue pain. Utilizing therapeutic desensitization techniques may allow for the direction of neuroplasticity in order to decrease pain.

Treating phantom limb pain: cryoablation of the posterior tibial nerve.

Phantom limb pain (PLP) is a complex pathophysiologic process involving both the central and peripheral nervous system for which there is no definitive treatment. The number of individuals living with amputated limbs is predicted to increase to 3.5 million by 2050, and up to 80% of these patients will have PLP. In this case report, we will demonstrate successful reduction of PLP in a patient with bilateral phantom toe pain utilizing nerve blockade and subsequent cryoablation of the posterior tibial nerves.

Altered intra- and inter-network brain functional connectivity in upper-limb amputees revealed through independent component analysis.

Although cerebral neuroplasticity following amputation has been observed, little is understood about how network-level functional reorganization occurs in the brain following upper-limb amputation. The objective of this study was to analyze alterations in brain network functional connectivity (FC) in upper-limb amputees (ULAs). This observational study included 40 ULAs and 40 healthy control subjects; all participants underwent resting-state functional magnetic resonance imaging. Changes in intra- and inter-network FC in ULAs were quantified using independent component analysis and brain network FC analysis. We also analyzed the correlation between FC and clinical manifestations, such as pain. We identified 11 independent components using independent component analysis from all subjects. In ULAs, intra-network FC was decreased in the left precuneus (precuneus gyrus) within the dorsal attention network and left precentral (precentral gyrus) within the auditory network; but increased in the left Parietal_Inf (inferior parietal, but supramarginal and angular gyri) within the ventral sensorimotor network, right Cerebelum_Crus2 (crus II of cerebellum) and left Temporal_Mid (middle temporal gyrus) within the ventral attention network, and left Rolandic_Oper (rolandic operculum) within the auditory network. ULAs also showed decreased inter-network FCs between the dorsal sensorimotor network and ventral sensorimotor network, the dorsal sensorimotor network and right frontoparietal network, and the dorsal sensorimotor network and dorsal attention network. Correlation analyses revealed negative correlations between inter-network FC changes and residual limb pain and phantom limb pain scores, but positive correlations between inter-network FC changes and daily activity hours of stump limb. These results show that post-amputation plasticity in ULAs is not restricted to local remapping; rather, it also occurs at a network level across several cortical regions. This observation provides additional insights into the plasticity of brain networks after upper-limb amputation, and could contribute to identification of the mechanisms underlying post-amputation pain.

Multicenter, Double-Blinded, Randomized, Active-Sham Controlled Clinical Study Design to Assess the Safety and Effectiveness of a Novel High Frequency Electric Nerve Block System in the Treatment of Post-Amputation Pain (The QUEST Study).

Background: Chronic pain that follows amputation of a limb is reported as "one of the most severe pains in the human experience," due to the magnitude of tissue injury and the multiple potential of pain generators at the local peripheral, spinal, and cortical levels. The Altius® System was developed to deliver high-frequency nerve block (HFNB) therapy via a cuff electrode applied to the peripheral nerve(s) and an implantable pulse generator. We report a novel clinical trial design for the first study of an active-implantable medical device in subjects with lower-limb post-amputation pain utilizing a multicenter, double-blinded, randomized, active-sham controlled clinical study protocol called QUEST, which is an ongoing investigational device exemption study to support United States Food and Drug Administration approval. Methods: The study enrollment of 180 subjects was completed in September 2021. Subjects were randomized 1:1 to the treatment group or the active-sham control group for the 3-month primary effectiveness and safety endpoints. After month 3, the active-sham control program group crossed over to the treatment program group and all subjects continued to the 12-month study endpoint. Study effectiveness success is determined by a superiority test between responder rates in the treatment and control groups at 3 months. A responder is defined as someone who experiences a 50% or greater reduction in pain scores - after a 30-minute treatment session - for more than 50% of all pain episodes in which the treatment was used. Discussion: The QUEST study design employs an active-sham control group to objectively assess the effectiveness of HFNB therapy. Additionally, the electronic diary repeated measures data collection in QUEST is expected to reduce the intra-subject variation typically observed in pain treatment studies. Finally, the longitudinal measurement of health-related quality of life and use of pain medication may, for example, show effectiveness in reducing opioid use over time.

Feasibility of Magnetic Resonance-Guided High-Intensity-Focused Ultrasound (MRgHIFU) Ablation of Stump Neuromas for the Relief of Chronic Postamputation Neuropathic Pain.

Up to 70% of limb amputees develop chronic postamputation neuropathic pain (CPANP) which includes phantom pain and residual limb neuropathic pain due to neuroma formation. CPANP often requires invasive procedures aimed at neuroma ablation. Five amputees received 6 noninvasive magnetic resonance-guided high-intensity-focused ultrasound MRgHIFU treatments ExAblate®, Insightec, Tirat-Carmel, Israel). Although ablative temperature (>65°C) at the neuroma was reached in only 1 patient, pain intensity dropped from 5.7 at baseline to 4.3 and back to 5.6 at 3 and 6 month follow-up. Post-treatment bone necrosis was demonstrated in 1 patient. Although no firm conclusion about the effectiveness of MRgHIFU for CPANP could be drawn, further studies are warranted.

Post-amputation pain among lower limb amputees in a tertiary care hospital in Jeddah, Saudi Arabia: A retrospective study.

OBJECTIVES: To estimate the prevalence of post- amputation pain among lower-limb amputees and its burden on their lives. METHODS: A retrospective patients record review of lower limb amputation surgeries was carried out at King Abdulaziz University Hospital, Jeddah, Saudi Arabia, between 2008-2019. e collected data included: patients demographics, surgical operations, chronic pain characteristics, functional impairment, and treatment. RESULTS: A total of 645 lower-limb amputations carried out on 509 patients, 104 (20.4%) patients had more than one amputation surgery carried out, and 40 (7.9%) patients having bilateral amputations. The estimated prevalence of chronic post-amputation pain among the lower-limb amputees was approximately 61.5%. Persistent postoperative neuropathic pain was the most common type of pain following amputation, followed by residual limb pain, then phantom limb pain. The most common cause of amputation was diabetes and its related complications (76%). The mean age at surgery was 57.46±12.02 years. Although diabetes was a common comorbid illness (95.6%), it had no correlation with the development of chronic post-amputation pain. However, peripheral vascular disease had a strong association (p=0.009), especially with the development of phantom limb pain (54.5%; p=0.016). The most common reason for functional impairment among the amputees was disability (52.7%), while only 6.6% said it was secondary to pain. CONCLUSION: Post-amputation pain is one of the major consequences of amputation. Pain was poorly managed among these patients. Special considerations should be obtained to manage these patients' pain and reduce their suffering.

A cartography of energy medicine: From subtle anatomy to energy physiology.

The field of energy medicine (EM) is perhaps the most controversial branch of integrative medicine. Its core concept - the existence of an invisible healing energy - has not yet been validated by Western medicine, and the mechanism(s) of action of its techniques have not been fully elucidated. This paper addresses these problems by marshalling several types of evidence: basic science research into electromagnetic fields (EMF), subjective sensations experienced when receiving EM treatments, and clairvoyant perceptions of EM in action. The latter two sources of information, while not solid enough to meet current standards of scientific rigor, can nonetheless generate important new information. A hypothesis is then developed to explain these findings. First, the main components of the human subtle energy system are presented: the "subtle anatomy" of the meridians, of the energy centers and of the biofield. Several representative EM techniques are then analyzed to determine which specific components of that energy structure they impact. Next, EM's mechanisms of action are explored by describing how these altered energy dynamics can affect biologic processes. This subject is termed "energy physiology", in parallel with conventional medicine's foundation in anatomy and physiology. Finally, potential research into energy physiology is outlined that focuses on several common but distinctive experiences which are not fully explained by the current mechanistic biomedical model. Plausible and testable energy-based explanations are proposed for phantom limb pain, emotional entrainment in groups, unusually rapid symptom response to EM, and the invisible templates that guide cell growth and differentiation. This analysis is intended to serve as a guide to future clinical and research explorations into the multidimensional nature of human beings. As Western medicine develops technologies that can generate objective empiric evidence in these subtle domains, we will be able to more fully understand the energetic components of health and illness.

Effectiveness of Mirror Therapy for Phantom Limb Pain: A Systematic Review and Meta-analysis.

OBJECTIVE: To evaluate the effectiveness of mirror therapy (MT) for phantom limb pain (PLP). DATA SOURCES: PubMed, EMBASE, Ovid MEDLINE, Scopus, Cochrane Library, Physiotherapy Evidence Database, CNKI, and WanFang Data were used to search for studies published up to March 31, 2021. STUDY SELECTION: Randomized controlled trials (RCTs) comparing the pain intensity of MT for PLP were performed. A total of 2094 articles were found. Among them, 10 were eligible for the final analysis. DATA EXTRACTION: The quality of the RCTs was assessed using the Physiotherapy Evidence Database (PEDro) scale by 2 independent reviewers. Outcome data were pooled according to follow-up intervals (1, 3, 6, and 12mo). Duration times were used as a basis for distinguishing subgroups. The primary evaluation was by visual analog scale. The PEDro scale was used to assess the methodological quality of studies. DATA SYNTHESIS: Meta-analysis revealed a statistically significant decrease in pain in the MT group vs the control group within 1 month (I2=0%; standardized mean difference [SMD]=-0.46, 95% confidence interval [CI], -0.79 to -0.13; P = .007). The patients with pain for longer than 1 year benefited more from MT (I2=0%; SMD=-0.46; 95% CI, -0.85 to -0.07; P = .02). CONCLUSIONS: MT has beneficial effects for patients with PLP in the short-term, as evidenced by their improved pain scores. There was no evidence that MT had a long-term effect, but that may be a product of limited data. For patients with long-term PLP, MT may be an effective treatment.

"Decreasing Postamputation Pain with the Regenerative Peripheral Nerve Interface (RPNI)".

Over 185,000 limb amputations are performed in the United States annually, many of which are due to the sequelae of peripheral vascular disease. Symptomatic neuromas remain a significant source of postamputation morbidity and contribute to both phantom limb (PLP) and residual limb pain (RLP). While many interventions have been proposed for the treatment of symptomatic neuromas, conventional methods lead to a high incidence of neuroma recurrence. Furthermore, these existing methods do not facilitate an ability to properly interface with myoelectric prosthetic devices. The Regenerative Peripheral Nerve Interface (RPNI) was developed to overcome these limitations. The RPNI consists of an autologous free muscle graft secured around the end of a transected nerve. The muscle graft provides regenerating axons with end organs to reinnervate, thereby preventing neuroma formation. We have shown that this simple, reproducible, and safe surgical technique successfully treats and prevents neuroma formation in major limb amputations. In this paper, we describe RPNI surgery in the setting of major limb amputation and highlight the promising results of RPNIs in our animal and clinical studies.

Transcranial Direct Current Stimulation for the Management of Neuropathic Pain: A Narrative Review.

BACKGROUND: Neuropathic pain (NP) is common and often resistant to conventional analgesics. Among different types of noninvasive brain stimulation techniques, transcranial direct current stimulation (tDCS) has been widely used to mitigate pain in patients with NP. OBJECTIVE: The aim of this study was to review the effects of tDCS on the management of various types of NP. STUDY DESIGN: Narrative review. METHODS: A PubMed search was conducted for articles published until October 1, 2020, using tDCS to treat NP. The key search phrase, transcranial direct current stimulation and pain, was used to identify potentially relevant articles. The following inclusion criteria were applied for article selection: (1) studies involving patients with NP and (2) studies that used tDCS to treat NP. Review articles were excluded from the analysis. RESULTS: A total of 524 potentially relevant articles were identified. After reading the titles and abstracts and assessing eligibility based on the full-text articles, 34 publications were included in our review. Overall, our results suggest that tDCS induced pain reduction in patients with NP due to stroke or spinal cord injury, multiple sclerosis, or trigeminal neuralgia. There is insufficient evidence to validate the efficacy of tDCS for treating other painful conditions, such as complex regional pain syndrome, phantom pain, or NP of various origins. LIMITATIONS: The review did not include studies indexed in databases other than PubMed. CONCLUSION: The results of the included studies suggest that tDCS may be beneficial in treating patients with NP due to stroke, spinal cord injury, multiple sclerosis, and trigeminal neuralgia. Further studies are recommended to validate the efficacy of tDCS in treating other types of NPs.