Severe Phantom Limb Pain Research Articles

The Coevolution of the Understanding and Treatment Modalities for Phantom Limb Pain

Phantom Limb Pain (PLP), an inappropriate sensation in a missing limb, is a post-amputation phenomenon that occurs in up to 80% of amputees. The specific sensations vary from person to person, but some common reported sensations include warmth or coldness, itching, tingling, and electric shock. Some patients also perceive a specific position or movement of the phantom limb. Most amputees experience PLP with varying degrees of intensity, frequency, and duration. About 5-10% of amputees continue to have severe PLP for many years after amputation. As technology and scientific understanding have evolved, phantom limb pain has become better understood over the centuries, from its first mention from Ambroise Pare in the 1600s to the usage of a variety of medication, medical therapy, and surgery options available today. Although the field of medicine does not yet have a curative treatment for PLP, treatment modalities have advanced from the use of wooden pegs to the latest and advanced prosthetics. By summarizing the growing understanding and evolution of treatment modalities for the medical condition from its first mention in the 16th century to the current 21st century, we can begin to appreciate the years of study and collaboration to current knowledge of phantom limb pain.

Detangling the Structural Neural Correlates Associated with Resting versus Dynamic Phantom Limb Pain Intensity Using a Voxel-based Morphometry Analysis.

The management of phantom limb pain (PLP) is still challenging due to a partial understanding of its neurophysiological mechanisms. Structural neuroimaging features are potential biomarkers. However, only a few studies assessed their correlations with clinical severity and treatment response. This study aims to explore the association between brain gray matter volume (GMV) with phantom limb manifestations severity and PLP improvement after neuromodulatory treatments (transcranial direct current stimulation and mirror therapy). Voxel-based morphometry analyses and functional decoding using a reverse inference term-based meta-analytic approach were used. We included 24 lower limb traumatic amputees with moderate to severe PLP. We found that alterations of cortical GMV were correlated with PLP severity but not with other clinical manifestations. Less PLP severity was associated with larger brain clusters GMV in the non-affected prefrontal, insula (non-affected mid-anterior region), and bilateral thalamus. However, only the insula cluster survived adjustments. Moreover, the reverse inference meta-analytic approach revealed that the found insula cluster is highly functionally connected to the contralateral insula and premotor cortices, and the decoded psychological processes related to this cluster were "rating," "sustained attention," "impulsivity, " and "suffering." Moreover, we found that responders to neuromodulatory treatment have higher GMV in somatosensory areas (total volume of S1 and S2) in the affected hemisphere at baseline, compared to non-responders, even after adjustments.

Relationships Among Phantom Limb Pain, Peripheral Sensations, and Cognition in People with Lower-Limb Loss

ABSTRACT Introduction After amputation, altered sensory input leads to cortical reorganization that partly explains phantom limb pain (PLP). However, many factors impact the PLP phenomenon, and modern conceptualizations of chronic pain including PLP integrate both peripheral inputs and central interpretation. Clinicians without functional MRI could benefit from clinical measures related to PLP to assess clinical presentations. The purpose of this pilot study was to identify peripheral sensation and cognition measures related to PLP to inform outcome measure selection in future PLP research. Methods This cross-sectional analysis included people with PLP of any age, sex, and amputation cause or level. Assessments included patient-reported residual limb pain and PLP using the Prosthesis Evaluation Questionnaire, peripheral sensation measures (light touch, temperature, vibration, two-point discrimination), and cognition measures (laterality recognition, trail making, clock drawing). Unadjusted Spearman ρ coefficients were reported. Results Eleven volunteers (48.5 ± 13.2 years) with lower-limb amputations (seven transtibial) of various causes (nine medical) participated. More severe PLP symptoms were associated with impaired peripheral sensation (light touch, ρ = 0.514; temperature, ρ = 0.756) and poorer cognition (laterality recognition, ρ = 0.524; trail making, ρ = 0.565). Residual limb pain was not correlated with cognition measures (ρ < 0.4). Conclusions This pilot study identified clinical measures assessing cognition and peripheral sensation impairments associated with worse PLP symptoms. Phantom limb pain was related to temperature and light touch sensation measures, but two-point discrimination was not associated with PLP consistent with past research. Laterality recognition was associated with PLP per prior research, and the association of PLP with the Trail Making Test in this pilot study suggests that the Trail Making Test may be an additional cognition measure potentially useful in future clinical research to document the PLP experience.

Clinical updates on phantom limb pain : German version

Most patients with amputation (up to 80 %) suffer from phantom limb pain postsurgery. These are often multimorbid patients who also have multiple risk factors for the development of chronic pain from a pain medicine perspective. Surgical removal of the body part and sectioning of peripheral nerves result in a lack of afferent feedback, followed by neuroplastic changes in the sensorimotor cortex. The experience of severe pain, peripheral, spinal, and cortical sensitization mechanisms, and changes in the body scheme contribute to chronic phantom limb pain. Psychosocial factors may also affect the course and the severity of the pain. Modern amputation medicine is an interdisciplinary responsibility. This review aims to provide an interdisciplinary overview of recent evidence-based and clinical knowledge. The scientific evidence for best practice is weak and contrasted by various clinical reports describing the polypragmatic use of drugs and interventional techniques. Approaches to restore the body scheme and integration of sensorimotor input are of importance. Modern techniques, including apps and virtual reality, offer an exciting supplement to already established approaches based on mirror therapy. Targeted prosthesis care helps to obtain or restore limb function and at the same time plays an important role reshaping the body scheme. Consequent prevention and treatment of severe postoperative pain and early integration of pharmacological and nonpharmacological interventions are required to reduce severe phantom limb pain. To obtain or restore body function, foresighted surgical planning and technique as well as an appropriate interdisciplinary management is needed.

Development of a Phantom Limb Pain Model in Rats: Behavioral and Histochemical Evaluation.

Therapeutic strategies targeting phantom limb pain (PLP) provide inadequate pain relief; therefore, a robust and clinically relevant animal model is necessary. Animal models of PLP are based on a deafferentation injury followed by autotomy behavior. Clinical studies have shown that the presence of pre-amputation pain increases the risk of developing PLP. In the current study, we used Sprague-Dawley male rats with formalin injections or constriction nerve injury at different sites or time points prior to axotomy to mimic clinical scenarios of pre-amputation inflammatory and neuropathic pain. Animals were scored daily for PLP autotomy behaviors, and several pain-related biomarkers were evaluated to discover possible underlying pathological changes. Majority displayed some degree of autotomy behavior following axotomy. Injury prior to axotomy led to more severe PLP behavior compared to animals without preceding injury. Autotomy behaviors were more directed toward the pretreatment insult origin, suggestive of pain memory. Increased levels of IL-1β in cerebrospinal fluid and enhanced microglial responses and the expression of NaV1.7 were observed in animals displaying more severe PLP outcomes. Decreased expression of GAD65/67 was consistent with greater PLP behavior. This study provides a preclinical basis for future understanding and treatment development in the management of PLP.

Auricular Therapy for Treating Phantom Limb Pain Accompanied by Jumping Residual Limb: A Short Review and Case Study.

Phantom limb pain (PLP) is a common complaint among patients after amputation, while jumping residual limb is a rare post-amputation complication, they rarely happen at the same time and both remain difficult to manage. At present, there is a paucity of literature on this topic, and no treatment has been proven effective for treating both of them. In the present brief report, we described a patient who developed severe PLP accompanied by jumping residual limb after below-the-knee amputation and she was treated by auricular therapy (AT) with satisfactory effect.Supplementary InformationThe online version contains supplementary material available at 10.1007/s40122-021-00236-1.

Clinical updates on phantom limb pain.

Most patients with amputation (up to 80%) suffer from phantom limb pain postsurgery. These are often multimorbid patients who also have multiple risk factors for the development of chronic pain from a pain medicine perspective. Surgical removal of the body part and sectioning of peripheral nerves result in a lack of afferent feedback, followed by neuroplastic changes in the sensorimotor cortex. The experience of severe pain, peripheral, spinal, and cortical sensitization mechanisms, and changes in the body scheme contribute to chronic phantom limb pain. Psychosocial factors may also affect the course and the severity of the pain. Modern amputation medicine is an interdisciplinary responsibility. This review aims to provide an interdisciplinary overview of recent evidence-based and clinical knowledge. The scientific evidence for best practice is weak and contrasted by various clinical reports describing the polypragmatic use of drugs and interventional techniques. Approaches to restore the body scheme and integration of sensorimotor input are of importance. Modern techniques, including apps and virtual reality, offer an exciting supplement to already established approaches based on mirror therapy. Targeted prosthesis care helps to obtain or restore limb function and at the same time plays an important role reshaping the body scheme. Consequent prevention and treatment of severe postoperative pain and early integration of pharmacological and nonpharmacological interventions are required to reduce severe phantom limb pain. To obtain or restore body function, foresighted surgical planning and technique as well as an appropriate interdisciplinary management is needed.

Management of severe phantom limb pain through a supported prescribing guideline

Management of severe phantom limb pain through a supported prescribing guideline

Successful Treatment of Phantom Limb Pain by 1 Hz Repetitive Transcranial Magnetic Stimulation Over Affected Supplementary Motor Complex: A Case Report.

A 37-year-old man with a right transfemoral amputation suffered from severe phantom limb pain (PLP). After targeting the affected supplementary motor complex (SMC) or primary motor cortex (PMC) using a neuro-navigation system with 800 stimuli of 1 Hz repetitive transcranial magnetic stimulation (rTMS) at 85% of resting motor threshold, the 1 Hz rTMS over SMC dramatically reduced his visual analog scale (VAS) of PLP from 7 to 0. However, the 1 Hz rTMS over PMC failed to reduce pain. To our knowledge, this is the first case report of a successfully treated severe PLP with a low frequency rTMS over SMC in affected hemisphere.

Oral ketamine for phantom limb pain: An option for challenging cases

Phantom limb pain (PLP) is a referred neuropathic pain perceived to arise from an amputated part of the body. It occurs in up to 80% of limb amputees and affects the patient's quality of life and rehabilitation.[1,2] The mechanisms of PLP remain unknown but involve both peripheral and central neural factors including activation of N-methyl-D-aspartate (NMDA) receptors.[2] Although ketamine, an NMDA receptor blocker, has been successfully used in many neuropathic pain conditions, its role in treating PLP is unclear.[3,4] We describe a challenging case of PLP where treatment with oral ketamine provided adequate relief.

Phantom Limb Pain From Spinal Sarcoma: A Case Report

Phantom limb pain is a frequent sequela of amputation. A high prevalence of residual limb pain and back pain also exists among amputees. We present a case of a new-onset severe phantom limb pain resulting from a metastatic spinal mass in an 81-year-old patient with a history of malignant sarcoma and an old hip disarticulation amputation. The metastatic lesion, upon imaging, was found to involve the L3 vertebra and caused moderate compression of the thecal sac on the right and severe right lateral recess stenosis. After the mass was resected, the patient's phantom limb pain resolved. Our case report demonstrates that spinal metastatic pathologies may be a cause of phantom limb pain and should be included in the differential diagnosis of new-onset phantom limb pain or a change in phantom limb pain.

Calcitonin for phantom limb pain in a pregnant woman

The use of calcitonin to relieve severe, treatment-refractory phantom limb pain (PLP) is reported. After an above-knee leg amputation, a 29-year-old pregnant woman (at eight weeks gestation) reported severe PLP (consistent scores of 9 or 10 on a 10-point pain severity scale). The pain persisted for more than two weeks and was not relieved by multiple regimens of opioid and nonopioid medications, including extremely high doses of i.v. fentanyl. On postamputation day 16, a 30-minute i.v. infusion of 200 IU of calcitonin (salmon) was administered; the woman reported transient excruciating pain during the final 5 minutes of the infusion. There was little overall change in her pain status over the next three days. On postinfusion day 4, the patient reported reductions in the frequency and severity of PLP episodes, and a trend of improved PLP symptom control was noted over the next 48 hours, allowing the pain management team to begin tapering some medication dosages and thus reduce the woman's overall narcotic exposure. The patient was discharged to a nursing facility several weeks later with relatively stable pain (scores of <7) on a regimen of carbamazepine, gabapentin, and oxycodone. She eventually delivered a healthy full-term baby. reduction in the frequency of PLP attacks and a lessening of pain intensity were observed after administration of calcitonin (salmon) by i.v. infusion in a pregnant patient. Calcitonin therapy was not associated with any apparent long-term adverse effects to the patient or infant.

Use of Yamamoto New Scalp Acupuncture for Treatment of Chronic, Severe Phantom Leg Pain

Abstract Background: Phantom limb pain (PLP) occurs in up to 85% of patients who have amputations and significantly worsens their quality of life. PLP is extremely difficult to treat, and common pain treatment is rarely effective. This case report describes the use of Yamamoto New Scalp Acupuncture (YNSA) to treat chronic severe PLP. Case: A 59-year-old man presented to an outpatient pain clinic with a chief complaint of chronic severe PLP after the left-femoral lower-third amputation that he had 21 years before. Intervention: YNSA was performed on the points representing the cranial nerves. Main Outcome Measures: PLP intensity, duration, and frequency were monitored to determine if the patient gained any pain relief from YNSA. Results: During the week after the thirteenth YNSA session, the patient reported a decrease in PLP intensity from 9±1 before the treatment to ∼1 or no PLP at all. Following the sixteenth YNSA session, the patient reported a decrease in the average duration of PLP (0.5±0.25 minutes)...

Successful use of Memantine in the treatment of severe phantom limb pain: case report and literature review

Phantom limb pain is a common and difficult neuropathic pain problem following limb amputation. Widespread pathophysiological processes in the central and peripheral nervous system have been implicated with the NMDA receptor likely to play a key role in the process. Conventional anti-neuropathic treatment with tricyclic antidepressants, anticonvulsants and ketamine are often either ineffective or cause unacceptable side-effects. Memantine is a clinically well tolerated NMDA receptor antagonist, licensed for use in Alzheimers dementia, that may offer a further therapeutic option when used early in the development of the condition. We describe the succesful use of memantine in the treatment of phantom limb pain to allow discontinuation of opioids with no side-effects.

Midazolam as an Effective Drug for Severe Phantom Limb Pain in a Patient After Undergoing Spinal Anesthesia for Two Consecutive Surgeries in the Contralateral Lower Limb

Recurrence or exacerbation of phantom limb pain induced by regional anesthesia including spinal anesthesia, epidural anesthesia, and peripheral nerve block has been described in a few reports. This is a rare phenomenon, but it can occur in any amputee with or without a history of previous phantom limb pain. We describe a case whose phantom pain of the amputated limb stump was twice induced by spinal anesthesia during two consecutive surgeries in the contralateral lower limb. It was revealed that midazolam was successful in treating this rare phantom limb pain after spinal anesthesia. Here, we discuss the management of phantom limb pain during spinal anesthesia and the anesthetic management for subsequent surgery in patients with previous spinal anesthesia-induced phantom limb pain.

Profound Pain Reduction After Induction of Memantine Treatment in Two Patients with Severe Phantom Limb Pain

We present the cases of two patients who suffered severe lower extremity injuries and subsequently developed phantom limb pain (PLP) that was refractory to high dose opioids and adjunctive pain medications. Both patients were receiving large doses of oral methadone, IV hydromorphone via a patient-controlled analgesia delivery system, and adjunctive medications including tricyclic antidepressants, nonsteroidal anti-inflammatory medications, and anti-epileptics. Despite these treatments, the patients had severe PLP. Upon induction of the oral N-methyl-D-aspartate receptor antagonist memantine, both patients had a profound reduction in their PLP without any apparent side effects from the medication.

Pulsed Radiofrequency Treatment of Lower Extremity Phantom Limb Pain

Phantom limb pain can be challenging to treat. We present a patient who developed severe phantom limb pain after revision of her lower extremity amputation due to the continued progression of peripheral vascular disease. Multiple treatment modalities had been tried without success. Pulsed radiofrequency has been successfully used to manage a number of pain syndromes. The present case report describes the use of pulsed radiofrequency treatment for phantom limb pain. The authors initially preformed regional blocks of femoral and sciatic nerve with 0.375% bupivicaine 15 cc and 50 microg clonidine to control the patient's pain. The blocks provided good pain relief but with limited duration. Based on reports of prolonged pain relief provided by pulsed radiofrequency treatment for other chronic pain conditions such as lumbrosacral spondylosis, we decided to apply this treatment to the patient's sciatic nerve. The patient underwent pulsed radiofrequency treatment with 2 cycles of 120 seconds at 42 degrees, pulse rate of 2 pulse/second, and pulse duration of 20 milliseconds. Our report shows that the sciatic nerve block with bupivicaine and clonidine, initiated approximately 3 years after amputation, produced modest short-term relief. The pulsed radiofrequency treatment resulted in long-term relief of phantom limb pain. The patient was able to wean herself off all oral medications and has been pain free for 4 months.

EMDR and Phantom Limb Pain: Theoretical Implications, Case Study, and Treatment Guidelines

This article reviews the literature on EMDR treatment of somatic complaints and describes the application of Shapiro’s Adaptive Information Processing (AIP) model in the treatment of phantom limb pain. The case study explores the use of EMDR with a 38-year-old man experiencing severe phantom limb pain 3 years after the loss of his leg and part of his pelvis in an accident. Despite treatment at several rehabilitation and pain centers during the 3 years, and the use of opiate medication, he continued to experience persistent pain. After 9 EMDR treatment sessions, the patient’s phantom limb pain was completely ablated, and he was taken off medication. Effects were maintained at 18-month follow-up. The clinical implications of this application of EMDR are explored.

Deep brain stimulation for chronic pain investigated with magnetoencephalography

Deep brain stimulation has shown remarkable potential in alleviating otherwise treatment-resistant chronic pain, but little is currently known about the underlying neural mechanisms. Here for the first time, we used noninvasive neuroimaging by magnetoencephalography to map changes in neural activity induced by deep brain stimulation in a patient with severe phantom limb pain. When the stimulator was turned off, the patient reported significant increases in subjective pain. Corresponding significant changes in neural activity were found in a network including the mid-anterior orbitofrontal and subgenual cingulate cortices; these areas are known to be involved in pain relief. Hence, they could potentially serve as future surgical targets to relieve chronic pain.

Self-Reported Treatments Used for Lower-Limb Phantom Pain: Descriptive Findings

Hanley MA, Ehde DM, Campbell KM, Osborn B, Smith DG. Self-reported treatments used for lower-limb phantom pain: descriptive findings. Objective To examine the types and relative frequency of treatments used for lower-limb phantom limb pain (PLP), including both pharmacologic and rehabilitative interventions. Design Cross-sectional survey. Setting Community-based survey from clinical databases. Participants Community-based sample (N=255) of persons with lower-limb amputations. Interventions Not applicable. Main Outcome Measures Intensity of PLP and type and helpfulness of treatments (both past and present) used for PLP. Results Although 72% of the sample (n=183) reported current PLP, 53% of the respondents with PLP (and 38% of those with severe PLP) had never used treatment for PLP. Those who had used treatment reported greater pain severity and interference. The most commonly used treatment modality was analgesic medication, including acetaminophen, opioids, and nonsteroidal anti-inflammatory drugs. Of the treatments surveyed, only opioids and chiropractic care were rated as moderately to extremely helpful by the majority of those who had tried them, and many pain interventions had been discontinued. Conclusions As hypothesized, a significant proportion of persons with PLP have not used treatment for this pain, and, among those who have used pain treatments, few treatments are perceived as substantially helpful. More research is needed to identify effective management strategies for PLP and to examine further patient perceptions of pain treatment.