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.

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.
OBJECTIVE: 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).
CONCLUSIONS: 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.

OBJECTIVE: 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.
METHODS: 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.\"
CONCLUSIONS: 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.

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.
UNASSIGNED: Trotz intensiver Forschung und Entwicklung von Systemen zur Wiederherstellung sensorischer Informationen sind diese bisher nur Gegenstände von Studienprotokollen. Ein neues nichtinvasives, Feedbacksystem übersetzt Druckbelastungen des Vor- und Rückfußes gangsynchronisiert in vibrotaktile Stimulationen eines Hautareals. Um die Authentizität zu steigern, kann diese Versorgung durch ein Operationsverfahren ergänzt werden. Die „targeted sensory reinnervation“ (TSR) beschreibt ein mikrochirurgisches Operationsverfahren, bei dem ein definiertes Hautareal am Amputationsstumpf zuerst denerviert und anschließend durch einen spezifischen, transponierten sensorischen Nerv aus der amputierten Gliedmaße reinnerviert wird. Am Stumpf entsteht eine sensorische Schnittstelle. Im Folgenden werden klinische und orthopädietechnische Versorgungspfade mit diesem innovativen vibrotaktilen Feedbacksystem dargestellt und das chirurgische Verfahren der TSR nach Amputation der unteren Extremität näher erläutert.

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.

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.

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.
CONCLUSIONS: 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.

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UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: 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.

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.