Prevalence and factors associated with psychological morbidity, phantom limb Pain in lower limb amputees.

BACKGROUND: Lower limb amputation can lead to psychological problems.There is a lack of data to evaluate the psychological problems and associated factors in lower limb amputees. AIM: Prevalence and factors associated with psychological disorder and phantom limb pain in lower limb amputees METHODS: It was a cross-sectional study with a consecutive sampling technique. Patients were assessed on the Hospital Anxiety and Depression Scale (HADS) for the presence of depression and anxiety disorder. DSM-5 diagnostic criteria for substance use disorder were used, andphantom limb pain was diagnosed as defined by Pare. RESULTS: 103 patients were included in the present study with a mean age of37.7 ± 14.5 yrs. The majorityof patients were males (87.4 %), married (69.9 %), on paid employment (95.1 %), and were of middle socioeconomic status (83.5 %). Most of the patients presented with roadside accident injuries (83.5 %)and had below-knee amputation (58.3 %). As per DSM-5, 38.8 % had a substance use disorder, out of which 35.9 % and 24.3 % had alcohol and tobacco use disorders, respectively. On HADS, 48.5 % had a presence of depressive disorder, and 30.1 % had anxiety disorder. The majority of patients (97.1 %) had phantom limb pain. Those from rural areas reported significantly more frequency of anxiety (x2-5.501; p-0.019) and depressive disorder (x2-7.009; p-0.008). Lower incomehad a significant positive association with depression (r-0.228; p-0.021) and phantom limb pain (U-22.500; p-0.008). CONCLUSION: The prevalence of psychiatric morbidity in lower-limb amputeeswas very high. The most common psychological morbidity was depression,followed by anxiety disorder and substance use disorders.Our findings reflect that we would benefit by including mental health professionals asintegral members of the multidisciplinary team to do an early psychological assessment and intervention, which would help prevent psychological illnesses and improve quality of life.

Long-Term Treatment of Chronic Postamputation Pain With Bioelectric Nerve Block: Twelve-Month Results of the Randomized, Double-Blinded, Cross-Over QUEST Study.

OBJECTIVE: The multicenter, randomized, double-blinded, active-sham controlled trial (high-freQUEncy nerve block for poST amputation pain [QUEST]) was conducted to show the safety and efficacy of a novel, peripherally placed high-frequency nerve block (HFNB) system in treating chronic postamputation pain (PAP) in patients with lower limb amputations. The primary outcomes from QUEST were reported previously. This study presents the long-term, single-cross-over, secondary outcomes of on-demand HFNB treatment for chronic PAP. MATERIALS AND METHODS: After the three-month randomized period, subjects in the active-sham group were crossed over to receive therapy for 12 months. Subjects self-administered HFNB therapy as needed and reported their pain (numerical rating scale [NRS]; range, 1-10) before and 30 and 120 minutes after each treatment. Pain medication use was reported throughout the study. Pain-days per week and quality of life (QOL) were assessed using the Brief Pain Inventory (BPI). Adverse events (AEs) were recorded for all subjects implanted for 12 months. RESULTS: Of 180 subjects implanted in QUEST, 164 (91%) were included in the cross-over period, and 146 (82%) completed follow-up. By month 12, average NRS pain in the combined cohort was reduced by 2.3 ± 2.2 points (95% CI, 1.7-2.8; p < 0.0001) 30 minutes after treatment and 2.9 ± 2.4 points (95% CI, 2.2-3.6; p < 0.0001) 120 minutes after treatment. Mean pain-days per week were significantly reduced (-3.5 ± 2.7 days; p < 0.001), and subject daily opioid use was reduced by 6.7 ± 29.0 morphine equivalent dose from baseline to month 12 (p = 0.013). Mean BPI-interference scores (QOL) improved by 2.7 ± 2.7 points from baseline (p < 0.001). The incidence of nonserious AEs and serious AEs was 72% (130/180) and 42% (76/180), respectively; serious device-related AEs occurred in 15 of 180 subjects (8%). CONCLUSION: Overall, HFNB delivered directly to the damaged peripheral nerve provided sustained, on-demand relief of acute PAP exacerbations, reduced opioid utilization, and improved QOL for patients with lower limb amputations with chronic PAP.

Clinical Characteristics Associated with the PLP-PLS Index, a New Potential Metric to Phenotype Phantom Limb Pain.

BACKGROUND: Phantom limb pain (PLP) is highly prevalent after amputation. However, the influence of non-painful sensations (PLS) remains unclear. This study examines the PLP-PLS index as a novel tool to differentiate PLP from PLS and explores the association of clinical factors with the index. METHODS: We conducted a cross-sectional analysis of baseline data from 112 participants in a previous factorial trial in patients with unilateral traumatic lower limb amputation. Linear regression models were used to examine the associations between the index and various demographic, psychological and clinical factors. Logistic and Poisson regression, and e-value calculation were utilized for sensitivity analyses. RESULTS: Adjusted multivariable linear regression models demonstrated significant associations of phantom movement sensation (ß: -1.532; 95% CI: -2.615 to -0.449; p = 0.006) and time since amputation (ß: 0.005; 95% CI: 0.0006 to 0.0101; p = 0.026) with the PLP-PLS index. These findings were confirmed by multivariable logistic regression (phantom movement sensation OR: 0.469; 95% CI: 0.200 to 1.099, p = 0.082; time since amputation OR: 1.003; 95% CI: 1.00003 to 1.007; p = 0.048) and sensitivity analyses. CONCLUSIONS: Time since amputation and phantom movement sensation likely reflect distinct phenotypes and potential mechanisms for PLP and PLS. The PLP-PLS index is a promising clinical tool for selecting therapies to prevent/treat PLP and for measuring treatment effects to modulate phantom pain. These findings emphasize the importance of understanding the mechanisms underlying PLP and PLS for improving clinical management and guiding future research.

Neural correlates of phantom motor execution: A functional neuroimaging systematic review and meta-analysis.

Phantom motor execution (PME) shows promise as a new treatment for phantom limb pain (PLP) by inducing motor-related analgesia and retraining the pain network activation. However, the current understanding of the neural correlates underlying PME is limited. Databases were systematically searched for multimodal neuroimaging studies to explore the neural correlates of PME. A narrative synthesis (17 studies, n = 328) and coordinate-based meta-analysis were performed to identify activation commonalities. Contrasting PME-vs-REST revealed differential activation of the supplementary motor area (SMA), post-central gyrus, and dorsolateral superior frontal gyrus; while PME-vs-ME revealed differential activation of the right anterior insula, anterior cingulate, left amygdala, and right striatum. Further narrative synthesis revealed a positive correlation between PME-induced brain activity and PLP intensity, and a specific connectivity pattern during PME on the SMA-M1 network compared to ME and motor imagery. Our results suggest that the PME represents a distinct type of motor network activation, partially overlapping with ME and motor imagery activations but with special activation of interoceptive regulation and mood-related regions. Thus, confirming its potential as a therapeutic approach for PLP.

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.

Sources of Rapid and Delayed New Lower Jaw Input in the Forepaw Barrel Subfield (FBS) in Rat Primary Somatosensory Cortex (SI) Following Forelimb Deafferentation.

Previously, we reported an immediate emergence of new lower jaw input to the anterior forepaw barrel subfield (FBS) in primary somatosensory cortex (SI) following forelimb deafferentation. However, a delay of 7 weeks or more post-amputation results in the presence of this new input to both anterior and posterior FBS. The immediate change suggests pre-existing latent lower jaw input in the FBS, whereas the delayed alteration implies the involvement of alternative sources. One possible source for immediate lower jaw responses is the neighboring lower jaw barrel subfield (LJBSF). We used anatomical tracers to investigate the possible projection of LJBSF to the FBS in normal and forelimb-amputated rats. Our findings are as follows: (1) anterograde tracer injection into LJBSF in normal and amputated rats labeled fibers and terminals exclusively in the anterior FBS; (2) retrograde tracer injection in the anterior FBS in normal and forelimb-amputated rats, heavily labeled cell bodies predominantly in the posterior LJBSF, with fewer in the anterior LJBSF; (3) retrograde tracer injection in the posterior FBS in normal and forelimb-amputated rats, sparsely labeled cell bodies in the posterior LJBSF; (4) retrograde tracer injection in anterior and posterior FBS in normal and forelimb-amputated rats, labeled cells exclusively in ventral posterior lateral (VPL) nucleus and posterior thalamus (PO); (5) retrograde tracer injection in LJBSF-labeled cell bodies exclusively in ventral posterior medial thalamic nucleus and PO. These findings suggest that LJBSF facilitates rapid lower jaw reorganization in the anterior FBS, whereas VPL and/or other subcortical sites provide a likely substrate for delayed reorganization observed in the posterior FBS.

A preliminary study exploring the effects of transcutaneous spinal cord stimulation on spinal excitability and phantom limb pain in people with a transtibial amputation.

Objective. Phantom limb pain (PLP) is debilitating and affects over 70% of people with lower-limb amputation. Other neuropathic pain conditions correspond with increased spinal excitability, which can be measured using reflexes andF-waves. Spinal cord neuromodulation can be used to reduce neuropathic pain in a variety of conditions and may affect spinal excitability, but has not been extensively used for treating PLP. Here, we propose using a non-invasive neuromodulation method, transcutaneous spinal cord stimulation (tSCS), to reduce PLP and modulate spinal excitability after transtibial amputation.Approach. We recruited three participants, two males (5- and 9-years post-amputation, traumatic and alcohol-induced neuropathy) and one female (3 months post-amputation, diabetic neuropathy) for this 5 d study. We measured pain using the McGill Pain Questionnaire (MPQ), visual analog scale (VAS), and pain pressure threshold (PPT) test. We measured spinal reflex and motoneuron excitability using posterior root-muscle (PRM) reflexes andF-waves, respectively. We delivered tSCS for 30 min d-1for 5 d.Main Results. After 5 d of tSCS, MPQ scores decreased by clinically-meaningful amounts for all participants from 34.0 ± 7.0-18.3 ± 6.8; however, there were no clinically-significant decreases in VAS scores. Two participants had increased PPTs across the residual limb (Day 1: 5.4 ± 1.6 lbf; Day 5: 11.4 ± 1.0 lbf).F-waves had normal latencies but small amplitudes. PRM reflexes had high thresholds (59.5 ± 6.1µC) and low amplitudes, suggesting that in PLP, the spinal cord is hypoexcitable. After 5 d of tSCS, reflex thresholds decreased significantly (38.6 ± 12.2µC;p< 0.001).Significance. These preliminary results in this non-placebo-controlled study suggest that, overall, limb amputation and PLP may be associated with reduced spinal excitability and tSCS can increase spinal excitability and reduce PLP.

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.

Repetitive Transcranial Magnetic Stimulation of the Dorsolateral Prefrontal Cortex for Phantom Limb Pain.

BACKGROUND: Phantom limb pain (PLP) is a prevalent and distressing occurrence in 60-80% of individuals who have undergone amputations. Recent research underscores the significance of maladaptive cortical plasticity in the genesis of PLP, emphasizing the importance of targeting cortical areas for therapeutic interventions. Repetitive transcranial magnetic stimulation (rTMS), a noninvasive tool for cortical stimulation, demonstrates effectiveness in treating various chronic pain conditions of neuropathic origin. Nevertheless, there exists a limited body of research investigating the application of rTMS as a therapeutic intervention specifically for managing PLP. Notably, the dorsolateral prefrontal cortex (DLPFC) plays a crucial role in central pain processing, suggesting its potential as a key therapeutic target in PLP treatment. There is a lack of adequate data regarding the effectiveness of DLPFC-targeting rTMS in alleviating the pain experienced by PLP patients. OBJECTIVE: In this study, our aim was to investigate the impact of 10 sessions of DLPFC-targeting rTMS on the pain status of individuals experiencing PLP. STUDY DESIGN: Randomized controlled trial. SETTING: Traumatic amputees reporting to the tertiary care center with PLP. METHODS: The study was approved by the Institute Ethics Committee (IECPG-299/27.04.2022) and registered in the Clinical Trials Registry of India (CTRI/2022/07/043938). Nineteen patients suffering from PLP were recruited and randomized into real or sham rTMS groups. In the real rTMS group, patients received 10 sessions of rTMS at the DLPFC contralateral to the amputation site. The rTMS, administered at 90% of the resting motor threshold (RMT), was delivered as 8 trains of 150 pulses per train at the rate of one Hz and an inter-train interval of 60 seconds. The total number of pulses per session was 1,200. The sham group received 10 sessions of sham rTMS through the perpendicular placement of an rTMS coil over the DLPFC. These sessions lasted for the same duration and included the same sounds as the real group but involved no active stimulation. The patients' pain status was evaluated using the Visual Analog Scale (VAS) at baseline, at the end of each session of real or sham rTMS and at the 15th, 30th, and 60th day after the the completion of real or sham therapy. RESULTS: A significant decrease in VAS scores was noted after 10 sessions of real rTMS that targeted the DLPFC, in contrast to the sham rTMS group. The real rTMS group's reduction in VAS scores also persisted during the follow-up. LIMITATIONS: A few patients had to drop out due to physical restrictions and financial constraints. Consequently, only a small number of individuals were able to complete the study protocol successfully. CONCLUSION: A regimen of 10 sessions of real rTMS of the DLPFC was associated with significant pain relief in patients with PLP, and the effects were sustained for 2 months. Therefore, the present study shows that rTMS of the DLPFC has potential as an effective therapeutic intervention for sustained pain relief in PLP patients.

Integrating Complementary Therapies in Managing Phantom Limb Pain: A Case Review.

OBJECTIVES: This paper describes phantom limb pain (PLP), its impact on patients, and the various treatment options, including pharmacologic and complementary therapies. It investigates the efficacy of incorporating complementary and alternative therapies, both invasive and noninvasive, for amputees who have not achieved satisfactory results with pharmacologic treatments and suffer from adverse drug events. Furthermore, with the predicted increase in limb amputations, it is crucial for nurses, as frontline providers, to understand PLP, be prepared to manage persistent pain and associated psychological and functional issues and educate patients and families about alternative treatment options. APPROACH: The review includes recent studies on pharmacologic interventions for PLP, case reports, and randomized clinical trials on non-pharmacologic complementary therapies, covering both invasive and noninvasive modalities. Studies from 2013 to 2022 were identified using the PubMed search engine with terms such as "Amputation," "phantom limb pain," "invasive therapies," and "non-invasive therapies." RESULTS AND CONCLUSION: The pathogenesis of PLP remains unclear, complicating the identification of causes and the selection of targeted therapies for each patient. Uncontrolled PLP can severely impact the quality of life, causing psychological distress and loss of productivity. Traditional pharmacologic therapy often requires supplementation with other options due to PLP's refractory nature. A comprehensive, multimodal treatment plan, including non-pharmacologic therapies, can enhance rehabilitation and reduce complications. Incorporating these therapies can decrease reliance on medications, particularly opioids, and mitigate side effects. Although many potential PLP treatments exist, further clinical studies are needed to determine their effectiveness and establish protocols for optimizing patient outcomes.

[Innovative noninvasive gait-synchronized vibrotactile feedback system : "I can feel myself walking again"]. / Innovatives nichtinvasives gangsynchrones vibrotaktiles Feedbacksystem : "Ich fühle, wie ich gehe".

Despite intensive research and development of systems for restoration of sensory information, these have so far only been the subject of study protocols. A new noninvasive feedback system translates pressure loads on the forefoot and hindfoot into gait-synchronized vibrotactile stimulation of a defined skin area. To increase the authenticity, this treatment can be supplemented by a surgical procedure. Targeted sensory reinnervation (TSR) describes a microsurgical procedure in which a defined skin area on the amputated stump of the residual limb is first denervated and then reinnervated by a specific, transposed sensory nerve harvested from the amputated part of the limb. This creates a sensory interface at the residual stump. This article presents the clinical and orthopedic technical treatment pathway with this innovative vibrotactile feedback system and explains in detail the surgical procedure of TSR after amputation of the lower limb.

Neuropsychiatric drugs and a neurophysiological marker as predictors of health-related quality of life in patients with phantom limb pain.

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. 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 eight 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 in the affected hemisphere (ICF), 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 two 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.

Phantom limb syndrome: from pathogenesis to treatment. A narrative review.

Phantom Limb Syndrome (PLS) can be defined as the disabling or painful sensation of the presence of a body part that is no longer present after its amputation. Anatomical changes involved in Phantom Limb Syndrome, occurring at peripheral, spinal and brain levels and include the formation of neuromas and scars, dorsal horn sensitization and plasticity, short-term and long-term modifications at molecular and topographical levels. The molecular reorganization processes of Phantom Limb Syndrome include NMDA receptors hyperactivation in the dorsal horn of the spinal column leading to inflammatory mechanisms both at a peripheral and central level. At the brain level, a central role has been recognized for sodium channels, BDNF and adenosine triphosphate receptors. In the paper we discuss current available pharmacological options with a final overview on non-pharmacological options in the pipeline.

A Novel Approach in Treating Phantom Limb Pain Using Erector Spinae Plane Block.

Phantom limb pain (PLP) is difficult to control, and patients frequently exhibit inadequate relief from medications or encounter unbearable side effects. We present here a novel application of erector spinae plane (ESP) block to manage PLP. Our patient is a 23-year-old, college student, diagnosed with high-grade osteosarcoma of the right humerus who underwent a right shoulder disarticulation. He reported PLP despite multimodal analgesia postoperatively. An ESP block using a high-frequency linear probe ultrasound was performed. A G23 spinal needle was advanced in-plane toward the right T3 transverse process. After negative aspiration, 20 mL of therapeutic solution containing bupivacaine 0.25%, lidocaine 1%, epinephrine 5 mcg/ml, and 40 mg methylprednisolone was injected. After the procedure, the patient reported that his PLP went down to NRS 1/10. He consistently reported to have an NRS score of 0-1/10 on succeeding consultations despite discontinuation of opioid and pregabalin. In literature, ESP block has been used as a regional technique for shoulder disarticulation surgery and other neuropathic pain conditions, but no account has shown its use for PLP treatment. The procedure was successfully done to alleviate the upper extremity phantom limb pain, significantly reduce analgesic requirements, and improve tolerance of physical therapy and overall quality of life.

Effect of transcranial direct current stimulation on supernumerary phantom limb pain in spinal cord injured patient: A case report.

BACKGROUND: Supernumerary phantom limb (SPL) sensation is the experience of additional limbs, either single or a pair of limbs. Unique to traumatic spinal cord injuries, we report effect of transcranial direct current stimulation (tDCS) on SPL pain in a patient with cervical cord injury. CASE SUMMARY: The subject was a 57-year-old man who was diagnosed with complete spinal cord injury (C6/C5, motor level; C5/C5, sensory level; AIS-A) approximately three months ago. After a period of 2 wk, we administered anodal tDCS over the motor cortex for 15 minutes at an intensity of 1.5 mA. Following that treatment, the patient experienced a decrease of SPL pain intensity and frequency, which lasted for 1 week after the end of treatment. CONCLUSION: Targeting the motor cortex through neuromodulation appears to be a promising option for the management of SPL pain.

Acute versus non-acute targeted muscle reinnervation for pain control following major limb amputation: A comparative study.

BACKGROUND: Targeted muscle reinnervation (TMR) has been shown to reduce phantom limb pain (PLP) and residual limb pain (RLP) after major limb amputation. However, the effect of the timing of surgery on pain control and quality of life outcomes is controversial. We conducted a retrospective study to compare the outcomes of acute TMR for pain prevention with non-acute TMR for the treatment of established pain. METHODS: All patients treated with TMR in our institution between January 2018 and December 2021 were evaluated at 6, 12, 18 and 24 months post-operatively. Pain intensity and quality of life outcomes were assessed using the Brief Pain Inventory (Pain Severity and Pain Interference scales) and Pain Catastrophizing Scale. Outcomes were compared between acute and non-acute TMR using the Wilcoxon ranked-sum test or Fisher's exact test as appropriate. Multilevel mixed-effects linear regression was used to account for repeat measures and potential pain confounders. RESULTS: Thirty-two patients with 38 major limb amputations were included. Acute TMR patients reported significantly lower RLP and PLP scores, pain interference and pain catastrophisation at all time points (p < 0.05). Acute TMR was significantly associated with lower pain severity and pain interference in a linear mixed-effects model accounting for patient age, gender, amputation indication, amputation site, time post-TMR and repeated surveys (p < 0.05). There was no significant difference in the complication rate (p = 0.51). CONCLUSION: Acute TMR was associated with clinically and statistically significant pain outcomes that were better than that in non-acute TMR. This suggests that TMR should be performed with preventative intent, when possible, as part of a multidisciplinary approach to pain management, rather than deferred until the development of chronic pain.

Primary 3-Month Outcomes of a Double-Blind Randomized Prospective Study (The QUEST Study) Assessing Effectiveness and Safety of Novel High-Frequency Electric Nerve Block System for Treatment of Post-Amputation Pain.

Purpose: This multicenter, randomized, double-blinded, active sham-controlled pivotal study was designed to assess the efficacy and safety of high-frequency nerve block treatment for chronic post-amputation and phantom limb pain. Patients and Methods: QUEST enrolled 180 unilateral lower-limb amputees with severe post-amputation pain, 170 of whom were implanted with the Altius device, were randomized 1:1 to active-sham or treatment groups and reached the primary endpoint. Responders were those subjects who received ≥50% pain relief 30 min after treatment in ≥50% of their self-initiated treatment sessions within the 3-month randomized period. Differences between the active treatment and sham control groups as well as numerous secondary outcomes were determined. Results: At 30-min, (primary outcome), 24.7% of the treatment group were responders compared to 7.1% of the control group (p=0.002). At 120-minutes following treatment, responder rates were 46.8% in the Treatment group and 22.2% in the Control group (p=0.001). Improvement in Brief Pain Inventory interference score of 2.3 ± 0.29 was significantly greater in treatment group than the 1.3 ± 0.26-point change in the Control group (p = 0.01). Opioid usage, although not significantly different, trended towards a greater reduction in the treatment group than in the control group. The incidence of adverse events did not differ significantly between the treatment and control groups. Conclusion: The primary outcomes of the study were met, and the majority of Treatment patients experienced a substantial improvement in PAP (regardless of meeting the study definition of a responder). The significant in PAP was associated with significantly improved QOL metrics, and a trend towards reduced opioid utilization compared to Control. These data indicate that Altius treatment represents a significant therapeutic advancement for lower-limb amputees suffering from chronic PAP.

Case Report: Phantom limb pain relief after cognitive multisensory rehabilitation.

Introduction: Relieving phantom limb pain (PLP) after amputation in patients resistant to conventional therapy remains a challenge. While the causes for PLP are unclear, one model suggests that maladaptive plasticity related to cortical remapping following amputation leads to altered mental body representations (MBR) and contributes to PLP. Cognitive Multisensory Rehabilitation (CMR) has led to reduced pain in other neurologic conditions by restoring MBR. This is the first study using CMR to relieve PLP. Methods: A 26-year-old woman experienced excruciating PLP after amputation of the third proximal part of the leg, performed after several unsuccessful treatments (i.e., epidural stimulator, surgeries, analgesics) for debilitating neuropathic pain in the left foot for six years with foot deformities resulting from herniated discs. The PLP was resistant to pain medication and mirror therapy. PLP rendered donning a prosthesis impossible. The patient received 35 CMR sessions (2×/day during weekdays, October-December 2012). CMR provides multisensory discrimination exercises on the healthy side and multisensory motor imagery exercises of present and past actions in both limbs to restore MBR and reduce PLP. Results: After CMR, PLP reduced from 6.5-9.5/10 to 0/10 for neuropathic pain with only 4-5.5/10 for muscular pain after exercising on the Numeric Pain Rating Scale. McGill Pain Questionnaire scores reduced from 39/78 to 5/78, and Identity (ID)-Pain scores reduced from 5/5 to 0/5. Her pain medication was reduced by at least 50% after discharge. At 10-month follow-up (9/2013), she no longer took Methadone or Fentanyl. After discharge, receiving CMR as outpatient, she learned to walk with a prosthesis, and gradually did not need crutches anymore to walk independently indoors and outdoors (9/2013). At present (3/2024), she no longer takes pain medication and walks independently with the prosthesis without assistive devices. PLP is under control. She addresses flare-ups with CMR exercises on her own, using multisensory motor imagery, bringing the pain down within 10-15 min. Conclusion: The case study seems to support the hypothesis that CMR restores MBR which may lead to long-term (12-year) PLP reduction. MBR restoration may be linked to restoring accurate multisensory motor imagery of the remaining and amputated limb regarding present and past actions.