To compare targeted muscle reinnervation (TMR) to "standard treatment" of neuroma excision and burying into muscle for postamputation pain.
To date, no intervention is consistently effective for ...neuroma-related residual limb or phantom limb pain (PLP). TMR is a nerve transfer procedure developed for prosthesis control, incidentally found to improve postamputation pain.
A prospective, randomized clinical trial was conducted. 28 amputees with chronic pain were assigned to standard treatment or TMR. Primary outcome was change between pre- and postoperative numerical rating scale (NRS, 0-10) pain scores for residual limb pain and PLP at 1 year. Secondary outcomes included NRS for all patients at final follow-up, PROMIS pain scales, neuroma size, and patient function.
In intention-to-treat analysis, changes in PLP scores at 1 year were 3.2 versus -0.2 (difference 3.4, adjusted confidence interval (aCI) -0.1 to 6.9, adjusted P = 0.06) for TMR and standard treatment, respectively. Changes in residual limb pain scores were 2.9 versus 0.9 (difference 1.9, aCI -0.5 to 4.4, P = 0.15). In longitudinal mixed model analysis, difference in change scores for PLP was significantly greater in the TMR group compared with standard treatment mean (aCI) = 3.5 (0.6, 6.3), P = 0.03. Reduction in residual limb pain was favorable for TMR (P = 0.10). At longest follow-up, including 3 crossover patients, results favored TMR over standard treatment.
In this first surgical RCT for the treatment of postamputation pain in major limb amputees, TMR improved PLP and trended toward improved residual limb pain compared with conventional neurectomy.
NCT02205385 at ClinicalTrials.gov.
With the development of neuroscience, substantial advances have been achieved in peripheral nerve regeneration over the past decades. However, peripheral nerve injury remains a critical public health ...problem because of the subsequent impairment or absence of sensorimotor function. Uncomfortable complications of peripheral nerve injury, such as chronic pain, can also cause problems for families and society. A number of studies have demonstrated that the proper functioning of the nervous system depends not only on a complete connection from the central nervous system to the surrounding targets at an anatomical level, but also on the continuous bilateral communication between the two. After peripheral nerve injury, the interruption of afferent and efferent signals can cause complex pathophysiological changes, including neurochemical alterations, modifications in the adaptability of excitatory and inhibitory neurons, and the reorganization of somatosensory and motor regions. This review discusses the close relationship between the cerebral cortex and peripheral nerves. We also focus on common therapies for peripheral nerve injury and summarize their potential mechanisms in relation to cortical plasticity. It has been suggested that cortical plasticity may be important for improving functional recovery after peripheral nerve damage. Further understanding of the potential common mechanisms between cortical reorganization and nerve injury will help to elucidate the pathophysiological processes of nerve injury, and may allow for the reduction of adverse consequences during peripheral nerve injury recovery. We also review the role that regulating reorganization mechanisms plays in functional recovery, and conclude with a suggestion to target cortical plasticity along with therapeutic interventions to promote peripheral nerve injury recovery.
Phantom limb pain (PLP) is a chronic neuropathic pain condition of a missing limb following amputation. Pain management is multi-modal, including various non-pharmacological therapies. The purpose of ...this scoping review was to investigate the evidence surrounding current non-pharmacological treatment modalities for PLP and provide insight into their clinical feasibility.
A systematic search was conducted using four databases (Medline, Embase, PsychInfo, and CINAHL) following the PRISMA-ScR method. Results from papers meeting the inclusion criteria were charted to summarize findings, demographics, and use of neuroimaging.
A total of 3387 papers were identified, and full texts of 142 eligible papers were assessed. Eleven treatment modalities for PLP were identified with varying levels of evidence. Overall, there were 25 RCTs, 58 case reports, and 59 a combination of pilot, quasi-experimental, observational, and other study designs.
Currently, the evidence surrounding most treatment modalities is limited and only a fraction of studies are supported by strong evidence. The findings of this review demonstrated a clear need to conduct more rigorous research with diverse study designs to better understand which modalities provide the most benefit and to incorporate neuroimaging to better determine the neural correlates of PLP and mechanisms of various treatments.
Implications for Rehabilitation
Phantom limb pain (PLP) is a prevalent and debilitating condition following amputation and health care professionals should incorporate an evidence-based pain management protocol into their rehabilitation program.
There exist a number of different non-pharmacological therapies to address PLP, however the scientific rigor and levels of evidence vary across modalities.
Prescription of interventions for PLP should consider individual patient differences, accessibility to the patient, and quite possibly, a multi-modal approach, particularly for those who also experience residual limb pain.
Imagery-based therapies provide the highest level of current evidence based on robust and large randomized control trials, are readily accessible, and are thus most recommended for relief of PLP.
Targeted muscle reinnervation (TMR) is a technique for the management of peripheral nerves in amputation. Phantom limb pain (PLP) and residual limb pain (RLP) trouble many patients after amputation, ...and TMR has been shown to reduce this pain when performed after the initial amputation. We hypothesize that TMR at the time of amputation may improve pain for patients after major upper-extremity amputation.
We conducted a retrospective review of patients who underwent major upper-extremity amputation with TMR performed at the time of the index amputation (early TMR). Phantom limb pain and RLP intensity and associated symptoms were assessed using the numeric rating scale (NRS), the Patient-Reported Outcome Measurement Information System (PROMIS) Pain Intensity Short-Form 3a, the Pain Behavior Short-Form 7a, and the Pain Interference Short-Form 8a. The TMR cohort was compared with benchmarked data from a sample of upper-extremity amputees.
Sixteen patients underwent early TMR and were compared with 55 benchmark patients. More than half of early TMR patients were without PLP (62%) compared with 24% of controls. Furthermore, half of all patients were free of RLP compared with 36% of controls. The median PROMIS PLP intensity score for the general sample was 47 versus 38 in the early TMR sample. Patients who underwent early TMR reported reduced pain behaviors and interference specific to PLP (50 vs 53 and 41 vs 50, respectively). The PROMIS RLP intensity score was lower in patients with early TMR (36 vs 47).
This study demonstrates that early TMR is a promising strategy for treating pain and improving the quality of life in the upper-extremity amputee. Early TMR may preclude the need for additional surgery and represents an important technique for peripheral nerve surgery.
Therapeutic IV.
Studies have suggested that targeted muscle reinnervation (TMR) can improve symptoms of neuroma pain (NP) and phantom limb pain (PLP) in patients.
Our primary objective was to measure changes in NP ...and PLP levels following TMR surgery at 4-time points (baseline, 3, 6- and 12-months postoperatively). Secondary aims included identification of the character and rate of any surgical complications and patients’ satisfaction with TMR.
A retrospective review of outcomes of 36 patients who underwent TMR surgery to treat intractable NP and/or PLP after major amputation of an upper (UL) or lower limb (LL) at a single centre in London, UK over 7 years. The surgical techniques, complications, and satisfaction with TMR are described.
Forty TMR procedures were performed on 36 patients. Thirty patients had complete data for NP and PLP levels at all pre-defined time points. Significant improvements (p<0.01) in both types of pain were observed for both upper and LL amputees. However, there were varying patterns of recovery. For example, UL amputees experienced worsening of PLP in the first few months post-operatively whereas surgical complications were more common in LL cases. Patients were overwhelmingly satisfied with the improvements in their symptoms (90%).
TMR surgery appeared to relieve both NP and PLP although the retrospective nature of this study limits the strength of this conclusion. However, complication rates were high, and it is crucial for surgeons and patients to fully understand the course and outcomes of this novel surgery prior to undertaking treatment.
: The neuromatrix theory of pain proposes that pain is a multidimensional experience produced by characteristic “neurosignature” patterns of nerve impulses generated by a widely distributed neural ...network—the “body‐self neuromatrix”—in the brain. These neurosignature patterns may be triggered by sensory inputs, but they may also be generated independently of them. Acute pains evoked by brief noxious inputs have been meticulously investigated by neuroscientists, and their sensory transmission mechanisms are generally well understood. In contrast, chronic pain syndromes, which are often characterized by severe pain associated with little or no discernable injury or pathology, remain a mystery. Furthermore, chronic psychological or physical stress is often associated with chronic pain, but the relationship is poorly understood. The neuromatrix theory of pain provides a new conceptual framework to examine these problems. It proposes that the output patterns of the body‐self neuromatrix activate perceptual, homeostatic, and behavioral programs after injury, pathology, or chronic stress. Pain, then, is produced by the output of a widely distributed neural network in the brain rather than directly by sensory input evoked by injury, inflammation, or other pathology. The neuromatrix, which is genetically determined and modified by sensory experience, is the primary mechanism that generates the neural pattern that produces pain. Its output pattern is determined by multiple influences, of which the somatic sensory input is only a part, that converge on the neuromatrix.
Phantom limb pain and traumatic neuromas are not commonly seen in neurosurgical practice. These conditions can present with similar symptoms; however, management of traumatic neuroma is often ...surgical, whereas phantom limb pain is treated with conservative measures.
A 77-year-old female patient with a long-standing history of an above-the-knee amputation experienced severe pain in her right posterior buttocks area for several years' duration, attributed to phantom limb pain, which radiated down the stump of her leg and was treated with a variety of conservative measures. A recent exacerbation of her pain led to a prolonged hospitalization with magnetic resonance imaging of her leg stump, revealing a mass in the sciatic notch, at a relative distance from the stump. The anatomical location of the mass on the sciatic nerve in the notch led to a presumed radiological diagnosis of nerve sheath tumor, for which she underwent excision. At surgery, a neuroma of the proximal portion of the transected sciatic nerve that had retracted from the amputated stump to the notch was diagnosed.
Traumatic neuromas of transected major nerves after limb amputation should be considered in the differential diagnosis of phantom limb pain.
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