Development Of Phantom Limb Pain Research Articles

Prophylactic Regenerative Peripheral Nerve Interface (RPNI) Surgery in Pediatric Lower Limb Amputation Patients.

To evaluate the prophylactic effect of Regenerative Peripheral Nerve Interface (RPNI) surgery on pediatric post-amputation pain. Chronic post-amputation pain is a debilitating and refractory sequela of limb amputation affecting up to 83% of pediatric patients with limb loss, resulting in disability and decreased quality of life. We postulate that prophylactic RPNI surgery performed during amputation may decrease the incidence of symptomatic neuroma and development of phantom limb pain, as well as limit analgesic use among pediatric patients with limb loss. Retrospective chart review was performed on pediatric patients between the ages of 8 and 21 years who underwent major lower limb amputation with and without RPNI surgery. Documented neuroma and phantom limb pain scores as well as analgesic use was recorded. Narcotic use was converted to milligrams morphine equivalents per day (MME/day) while overall analgesic use was converted to Medication Quantification Scale version III (MQSIII) scores. Analysis was performed using Stata. Forty-four pediatric patients were identified; 25 RPNI patients and 19 controls. Seventy-nine percent of control patients developed chronic post-amputation pain versus 21% of RPNI patients (P<0.001). Among the patients who developed post-amputation pain, 20% of controls developed clinical neuroma pain, compared to 0% of RPNI patients (P<0.001). Additionally, RPNI patients demonstrated a significant decrease in pain score (P=0.007) and narcotic usage (P<0.01), compared to controls. Overall analgesic use did not vary significantly between groups. Prophylactic RPNI surgery shows promise for pediatric patients undergoing major lower limb amputation by preventing both symptomatic neuromas and possibly the development of phantom limb pain.

Phantom limb pain: actual concepts of pathophysiology and therapeutic targets

In the review, we present the main pathogenetic mechanisms of the development of phantom limb pain (PLP) after limb amputation, the prevalence of which can reach 87%. The exact mechanism of PLP remains unknown. The involvement of peripheral and central mechanisms of the formation of PLP is assumed. Peripheral mechanisms include increased excitability and the formation of ectopic activity in the amputation neuromas and in the ganglion cells of the dorsal roots of the spinal cord. The central mechanisms are represented by central sensitization in the dorsal horns of the spinal cord with the development of the “wind up” phenomenon, reorganization processes in the thalamus and cortex with thalamic and cortical remapping, and proprioceptive memory. Also significant is the neuromatrix theory, the reduction of feedback from the visual and other sensory systems after deafferentation. PLP therapy methods focused on central mechanisms are: spinal cord stimulation, transcutaneous electrical neurostimulation, deep brain stimulation, non-invasive and invasive methods of cerebral cortex stimulation, mirror therapy, virtual and augmented reality technologies, movement representation and its modification “phantom exercises”. In addition, pharmacologic treatment options based on PLP mechanisms can be used: NMDA receptor antagonists, anticonvulsants, tricyclic antidepressants, opioids.

Pain and Reorganization after Amputation: Is Interoceptive Prediction a Key?

There is an ongoing discussion on the relevance of brain reorganization following amputation for phantom limb pain. Recent attempts to provide explanations for seemingly controversial findings—specifically, maladaptive plasticity versus persistent functional representation as a complementary process—acknowledged that reorganization in the primary somatosensory cortex is not sufficient to explain phantom limb pain satisfactorily. Here we provide theoretical considerations that might help integrate the data reviewed and suppose a possible additional driver of the development of phantom limb pain—namely, an error in interoceptive predictions to somatosensory sensations and movements of the missing limb. Finally, we derive empirically testable consequences based on our considerations to guide future research.

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.

Novel Approaches to Reduce Symptomatic Neuroma Pain After Limb Amputation

A considerable number of major limb amputation patients will develop symptomatic neuromas within the residual limb. There has been a paradigm shift in the surgical treatment of symptomatic neuromas from techniques that attempt to interrupt axonal regeneration in favor of techniques that permit reinnervation. In addition, growing evidence suggests that successful treatment of peripheral nerve pain may diminish the development of phantom limb pain. We discuss novel surgical techniques that seek to prevent neuroma formation and in turn reduce phantom limb pain. Targeted muscle reinnervation and regenerative peripheral nerve interface surgery provide regenerating peripheral nerves denervated targets for reinnervation thus reducing the number of free axons available to form neuromas. While very different in technique, both approaches decrease the formation of symptomatic neuromas. In doing so, these methods reduce the experience of residual limb pain and phantom limb pain. Implementation of innovative surgical techniques after peripheral nerve transection can transform the management of postamputation pain. Decreasing the impact of neuroma pain and phantom limb pain will facilitate prosthetic rehabilitation, decrease analgesic use, and improve quality of life after limb amputation.

Factors affecting phantom limb pain in patients undergoing amputation: retrospective study.

The efficacy of preemptive analgesia for prevention of phantom limb pain has been controversial although pain management before amputation is empirically important. The aim of this study was to determine the associated factors with perioperative phantom limb pain. Following approval by the Medical Ethics Committee in our university, medical records of patients receiving limb amputation surgery in our hospital between April 1, 2013 and October 31, 2017 were retrospectively reviewed. To determine which pre-operative factors could affect the development of phantom limb pain, we performed univariate analysis to find candidate factors (p < 0.05), and then did multivariate regression analysis. Incidence of phantom limb pain was 50% (22/44). There was no difference between the groups in types of anesthesia and post-operative pain levels. The multivariate logistic regression including possible confounders suggested that diabetes mellitus and uncontrollable preoperative pain with non-steroidal anti-inflammatory drugs (NSAIDs) were independently associated with the development of phantom limb pain (Adjusted odds ratio (OR) 0.238 [95% confidential interval (CI) 0.0643-0.883], p = 0.032, Adjusted OR 6.360 [95% CI 1.280-31.50], p = 0.024, respectively). The types of anesthesia and the degree of postoperative pain were not related to the development of phantom limb pain. The present data suggest that insufficient preoperative pain with NSAIDs and diabetes mellitus would give an impact on the development of phantom limb pain.

Effect of pain on deafferentation-induced modulation of somatosensory evoked potentials.

There is a large body of evidence showing substantial sensorimotor reorganizations after an amputation. These reorganizations are believed to contribute to the development of phantom limb pain, but alternatively, pain might influence the plasticity triggered by the deafferentation. The aim of this study was to test whether pain impacts on deafferentation-induced plasticity in the somatosensory pathways. Fifteen healthy subjects participated in 2 experimental sessions (Pain, No Pain) in which somatosensory evoked potentials (SSEPs) associated with electrical stimulation of the ulnar nerve were assessed before and after temporary ischemic deafferentation induced by inflation of a cuff around the wrist. In the Pain session capsaicin cream was applied on the dorsum of the hand 30 minutes prior to cuff inflation. Results show that pain decreased the amplitude of the N20 (main effect of condition, p = 0.033), with a similar trend for the P25. Temporary ischemic deafferentation had a significant effect on SSEPs (main effect of time), with an increase in the P25 (p = 0.013) and the P45 amplitude (p = 0.005), together with a reduction of the P90 amplitude (p = 0.002). Finally, a significant time x condition interaction, reflecting state-dependent plasticity, was found for the P90 only, the presence of pain decreasing the reduction of amplitude observed in response to deafferentation. In conclusion, these results show that nociceptive input can influence the plasticity induced by a deafferentation, which could be a contributing factor in the cortical somatosensory reorganization observed in chronic pain populations.

Reversal of phantom pain and hand-to-face remapping after brachial plexus avulsion.

Following left brachial plexus avulsion, a 20‐year‐old man had phantom limb pain and remapping of sensation from his paralyzed hand onto his face. Mirror therapy (15 min daily, 5 days/week) led immediately to good movement of the phantom limb with decreased pain. Within 2 weeks following nerve graft surgery, remapping of hand sensation onto the face disappeared along with resolution of phantom limb pain. Mirror therapy coupled with nerve grafting may relieve phantom limb pain due to brachial plexus avulsion and reverse hand‐to‐face remapping, suggesting that both peripheral and central mechanisms mediate development of phantom limb pain and cortical reorganization/neuroplasticity after brachial plexus avulsion.

Relationship between chronic pain and brain reorganization after deafferentation: A systematic review of functional MRI findings.

BackgroundMechanisms underlying the development of phantom limb pain and neuropathic pain after limb amputation and spinal cord injury, respectively, are poorly understood. The goal of this systematic review was to assess the robustness of evidence in support of “maladaptive plasticity” emerging from applications of advanced functional magnetic resonance imaging (MRI).MethodsUsing MeSH heading search terms in PubMed and SCOPUS, a systematic review was performed querying published manuscripts.ResultsFrom 146 candidate publications, 10 were identified as meeting the inclusion criteria. Results from fMRI investigations provided some level of support for maladaptive cortical plasticity, including longitudinal studies that demonstrated a change in functional organization related to decreases in pain. However, a number of studies have reported no relationship between reorganization, pain and deafferentation, and emerging evidence has also suggested the opposite — that is, chronic pain is associated with preserved cortical function.ConclusionBased solely on advanced functional neuroimaging results, there is only limited evidence for a relationship between chronic pain intensity and reorganization after deafferentation. The review demonstrates the need for additional neuroimaging studies to clarify the relationship between chronic pain and reorganization.

Development of phantom limb pain after femoral nerve block.

Historically, phantom limb pain (PLP) develops in 50–80% of amputees and may arise within days following an amputation for reasons presently not well understood. Our case involves a 29-year-old male with previous surgical amputation who develops PLP after the performance of a femoral nerve block. Although there have been documented cases of reactivation of PLP in amputees after neuraxial technique, there have been no reported events associated with femoral nerve blockade. We base our discussion on the theory that symptoms of phantom limb pain are of neuropathic origin and attempt to elaborate the link between regional anesthesia and PLP. Further investigation and understanding of PLP itself will hopefully uncover a relationship between peripheral nerve blocks targeting an affected limb and the subsequent development of this phenomenon, allowing physicians to take appropriate steps in prevention and treatment.

Phantom limb pain: mechanisms and treatment approaches.

The vast amount of research over the past decades has significantly added to our knowledge of phantom limb pain. Multiple factors including site of amputation or presence of preamputation pain have been found to have a positive correlation with the development of phantom limb pain. The paradigms of proposed mechanisms have shifted over the past years from the psychogenic theory to peripheral and central neural changes involving cortical reorganization. More recently, the role of mirror neurons in the brain has been proposed in the generation of phantom pain. A wide variety of treatment approaches have been employed, but mechanism-based specific treatment guidelines are yet to evolve. Phantom limb pain is considered a neuropathic pain, and most treatment recommendations are based on recommendations for neuropathic pain syndromes. Mirror therapy, a relatively recently proposed therapy for phantom limb pain, has mixed results in randomized controlled trials. Most successful treatment outcomes include multidisciplinary measures. This paper attempts to review and summarize recent research relative to the proposed mechanisms of and treatments for phantom limb pain.

Preamputation Mirror Therapy May Prevent Development of Phantom Limb Pain: A Case Series

We report the cases of 4 patients who performed daily mirror therapy for 2 wk before undergoing elective limb amputation. One patient experienced no phantom limb pain (PLP). Two patients experienced rare episodes of mild PLP without effect on their participation in physical therapy (PT) or their quality of life. One patient reported daily, brief episodes of moderate PLP without effect on his participation in PT or his stated quality of life. These results indicate that preoperative mirror therapy may improve postamputation PT compliance and decrease the incidence of PLP. Future prospective studies are needed to confirm the results of this case series.

Phantomschmerzen – Pathomechanismen und Therapieansätze

About 80 % of all extremity amputations suffer from phantom limb pain following the operation. In this context, it is important to differentiate between painful phantom limb sensations, non-painful phantom limb sensations and residual limb pain. The pathophysiology of phantom limb pain is not fully understood. Current research findings ascribe a major pathophysiological role to cortical changes as well as a disturbed body perception. Peripheral and spinal mechanisms appear less relevant in the development of phantom limb pain. An essential part of the therapy is the pharmacological treatment with antidepressants, anticonvulsives and opioids. Another significant aspect of therapy is senso-motory training, important to mention here would be mirror therapy, lateralisation and motor imaging. In case of an elective amputation, an epidural or axiliar plexus catheter should be considered prior to the amputation. The perioperative treatment with ketamine is debated.

Continuous brachial plexus blockade in combination with the NMDA receptor antagonist memantine prevents phantom pain in acute traumatic upper limb amputees

Background Hyperexcitability of N-methyl- d-aspartate acid (NMDA) receptors may play an important role in the development of phantom limb pain (PLP). Aim of the study To investigate whether early treatment with the NMDA antagonist memantine attenuates phantom pain memory formation in traumatic amputees. Methods In a randomized, double-blind, controlled trial 19 patients with acute traumatic amputation of the upper extremity were investigated. All patients received postoperative analgesia by continuous brachial plexus anesthesia (ropivacaine 0.375% 5 ml/h) for at least 7 days. In addition, the patients received either memantine (20–30 mg daily, n = 10) or placebo ( n = 9) for 4 weeks. Results Memantine treatment reduced the number of requested ropivacacine bolus injections during the first week and resulted in a significant decrease of PLP prevalence and intensity at 4 weeks and 6 months follow up, but not at 12 months follow up. Conclusions We conclude that memantine can reduce intensity of phantom limb pain and might also prevent the development of PLP. However, despite the very early begin of treatment; no long-term effect on established PLP was evident.

Kontinuierliche interscalenäre Plexusblockade bei einem dreijährigen Kind nach Armamputation - Ein Fallbericht

Amputations of extremities, especially in the childhood, impose high demands on the perioperative management. Apart from the intraoperative care of these children, the postoperative pain therapy has to do one's utmost in the avoidance of the development of phantom limb pain, which can, especially in the childhood, be associated with far reaching psychological consequences. We report the case of a 3-year old boy who had to undergo exarticualtion of his left arm due to an osteosarcoma of the humerus. The perioperative pain management was performed by a preoperatively placed interscalene catheter and infusion of 0.2 % ropivacaine. Within the first six days postoperatively complete pain relief could be ensured with this analgetic regimen.

Phantom limb pain: aspects of neuroplasticity and intervention

Phantom-limb pain is a common sequel of amputation, occurring in up to 80 % of the amputee population. It must be differentiated from non-painful phantom phenomena, residual-limb pain, and non-painful residual-limb phenomena. A comprehensive model of phantom-limb pain is presented that assigns a major role to pain occurring before the amputation and to central as well as peripheral changes related to it. Special emphasis is put on the role of cortical reorganization in the development of phantom limb pain. Finally, new approaches to the prevention and treatment of phantom limb pain are presented that have a positive influence on phantom limb pain by preventing or reversing cortical reorganization.

Phantom Limb Pain and Chemotherapy in Pediatric Amputees

To determine the frequency of phantom limb pain in pediatric patients with cancer-related amputations and the relationship between phantom limb pain and chemotherapy (CHRx). We retrospectively reviewed the medical records of all pediatric patients who underwent major limb amputations between 5 and 17 years of age during the period from Oct. 1, 1983, to Oct. 1, 1993, and were treated at the Mayo Clinic. One investigator reviewed 293 medical records and selected cases on the basis of specific inclusion and exclusion criteria. The study group consisted of 75 patients (67 with cancer-related and 8 with trauma-associated amputations). All reports of phantom limb pain and its temporal relationship to administration of CHRx were recorded. Data were analyzed by use of descriptive statistics. Phantom limb pain was reported in 48% of patients with cancer-related amputations in comparison with 12% of patients with trauma-associated amputations. Among patients with cancer, phantom limb pain was experienced by 74% who were exposed to CHRx before or at the time of amputation, 44% who received CHRx after amputation, and 12% who never received CHRx. Patients with trauma-related amputations and those who did not receive CHRx reported phantom limb pain at similar intervals after amputation (a mean of 6 days). In comparison, 76% of patients with cancer and a history of exposure to CHRx reported phantom limb pain within 72 hours after amputation. Three of four patients who first received CHRx after amputation reported phantom limb pain on the day CHRx was begun (a mean of 12.3 days after amputation). Our observations suggest that (1) phantom limb pain occurs more often in pediatric amputees with cancer than in those with trauma and (2) the hypothesis that CHRx may be a risk factor in the development of phantom limb pain in pediatric amputees should be investigated further.