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Journal of the American College of... Oct 2023Outcomes of targeted muscle reinnervation (TMR) and regenerative peripheral nerve interface (RPNI) in the oncologic population are limited. We sought to examine the...
BACKGROUND
Outcomes of targeted muscle reinnervation (TMR) and regenerative peripheral nerve interface (RPNI) in the oncologic population are limited. We sought to examine the safety and effectiveness of TMR and RPNI in controlling postamputation pain in the oncologic population.
STUDY DESIGN
A retrospective cohort study of consecutive patients who underwent oncologic amputation followed by immediate TMR or RPNI was conducted from November 2018 to May 2022. The primary study outcome was postamputation pain, assessed using the Numeric Pain Scale and Patient-Reported Outcomes Measurement Information System (PROMIS) for residual limb pain (RLP) and phantom limb pain (PLP). Secondary outcomes included postoperative complications, tumor recurrence, and opioid use.
RESULTS
Sixty-three patients were evaluated for a mean follow-up period of 11.3 months. The majority of patients (65.1%) had a history of previous limb salvage. At final follow-up, patients had an average Numeric Pain Scale score for RLP of 1.3 ± 2.2 and for PLP, 1.9 ± 2.6. The final average raw PROMIS measures were pain intensity 6.2 ± 2.9 (T-score 43.5), pain interference 14.6 ± 8.3 (T-score 55.0), and pain behavior 39.0 ± 22.1 (T-score 53.4). Patient opioid use decreased from 85.7% preoperatively to 37.7% postoperatively and morphine milligram equivalents decreased from a mean of 52.4 ± 53.0 preoperatively to 20.2 ± 38.4 postoperatively.
CONCLUSIONS
In the oncologic population TMR and RPNI are safe surgical techniques associated with significant reductions in RLP, PLP, and improvements in patient-reported outcomes. This study provides evidence for the routine incorporation of TMR and RPNI in the multidisciplinary care of oncologic amputees.
Topics: Humans; Amputees; Retrospective Studies; Analgesics, Opioid; Chronic Pain; Peripheral Nerves; Muscles
PubMed: 37278406
DOI: 10.1097/XCS.0000000000000778 -
Regional Anesthesia and Pain Medicine Sep 2023We previously reported that a 6-day continuous peripheral nerve block reduces established postamputation phantom pain. To provide patients and providers with the... (Randomized Controlled Trial)
Randomized Controlled Trial
Patient-centered results from a multicenter study of continuous peripheral nerve blocks and postamputation phantom and residual limb pain: secondary outcomes from a randomized, clinical trial.
INTRODUCTION
We previously reported that a 6-day continuous peripheral nerve block reduces established postamputation phantom pain. To provide patients and providers with the information to best inform treatment decisions, here we reanalyze the data and present the results in a more patient-centered format. We also provide information on patient-defined clinically relevant benefits to facilitate evaluation of available studies and guide future trial design.
METHODS
The original trial enrolled participants with a limb amputation and phantom pain who were randomized to receive a 6-day continuous peripheral nerve block(s) of either ropivacaine (n=71) or saline (n=73) in a double-masked fashion. Here we calculate the percentage of each treatment group that experienced a clinically relevant improvement as defined by previous studies as well as present what the participants of our study defined as small, medium, and large analgesic improvements using the 7-point ordinal Patient Global Impression of Change scale.
RESULTS
Among patients who were given a 6-day ropivacaine infusion, 57% experienced at least a 2-point improvement on the 11-point numeric rating scale in their average and worst phantom pain 4 weeks postbaseline as compared with 26% (p<0.001) for average and 25% (p<0.001) for worst pain in patients given a placebo infusion. At 4 weeks, the percentage of participants rating their pain as improved was 53% for the active vs 30% for the placebo groups (95% CI 1.7 (1.1, 2.7), p0.008). For all patients combined, the median (IQR) phantom pain Numeric Rating Scale improvements at 4 weeks considered small, medium, and large were 2 (0-2), 3 (2-5), and 5 (3-7), respectively. The median improvements in the Brief Pain Inventory interference subscale (0-70) associated with small, medium, and large analgesic changes were 8 (1-18), 22 (14-31), and 39 (26-47).
CONCLUSIONS
Among patients with postamputation phantom pain, a continuous peripheral nerve block more than doubles the chance of a clinically relevant improvement in pain intensity. Amputees with phantom and/or residual limb pain rate analgesic improvements as clinically relevant similarly to other chronic pain etiologies, although their smallest relevant improvement in the Brief Pain Inventory was significantly larger than previously published values.
TRIAL REGISTRATION NUMBER
NCT01824082.
Topics: Humans; Phantom Limb; Ropivacaine; Pain, Postoperative; Peripheral Nerves; Patient-Centered Care
PubMed: 36894197
DOI: 10.1136/rapm-2023-104389 -
Regional Anesthesia and Pain Medicine Jun 2024Injury to saphenous nerve branches is frequent during knee surgery and can result in chronic pain. This saphenous neuralgia remains challenging to treat. Peripheral...
BACKGROUND
Injury to saphenous nerve branches is frequent during knee surgery and can result in chronic pain. This saphenous neuralgia remains challenging to treat. Peripheral nerve stimulation (PNS) is a new potential non-pharmacologic treatment option. We present our outcomes experience using this technology in 12 patients.
METHODS
We retrospectively reviewed PNS placement for saphenous neuralgia between 2000 and 2022 at a single institution. Demographic information was collected as well as response to the device. Four-question short-form Patient-Reported Outcome Measurement Information System (PROMIS) Scores were collected before and 2 weeks, 6 weeks, and 6 months postprocedure. Specific scores included pain interference and behavior, functional mobility, depression, anxiety, and sleep impairment. Change in pain interference measured by the short-form PROMIS tool at 6 months was chosen as the primary outcome.
RESULTS
Twelve patients met inclusion criteria, with 10 patients having the full 6-month follow-up. In these 10 patients, the mean change from baseline in the short-form adjusted pain interference score (greater difference means improved pain) at 6 months was 5.8 (SD 6.5). Among all patients, average follow-up was 11.5 months (range 3-35 months). Most patients' symptoms developed after knee surgery (84%). Prior to PNS, patients underwent other treatments including cryoablation (8%), radiofrequency ablation (16%), saphenous neurectomy (16%), or surgical release of adjacent nerves (25%). Ten patients (83%) reported any improvement in symptoms while two reported no benefit. Complications occurred in four patients (33%). Two patients had the device removed and a third discontinued use. PROMIS Scores for pain, functional mobility, mood, and sleep impairment all improved.
DISCUSSION
Limited effective treatments exist for saphenous neuralgia. Our case series demonstrates the potential of PNS as a treatment for saphenous neuralgia. Comparative effectiveness studies are warranted to assess whether our effect size is clinically relevant.
Topics: Humans; Male; Female; Retrospective Studies; Middle Aged; Aged; Neuralgia; Treatment Outcome; Pain Measurement; Transcutaneous Electric Nerve Stimulation; Peripheral Nerves; Adult; Electric Stimulation Therapy; Patient Reported Outcome Measures
PubMed: 38050145
DOI: 10.1136/rapm-2023-104538 -
Muscle & Nerve Jan 2024Merosin is a protein complex located in the basement membrane of skeletal muscles and laminin α2-containing regions of the central and peripheral nervous systems....
INTRODUCTION/AIMS
Merosin is a protein complex located in the basement membrane of skeletal muscles and laminin α2-containing regions of the central and peripheral nervous systems. However, because of the prominence of muscle-related symptoms, peripheral neuropathy associated with merosin-deficient congenital muscular dystrophy type 1A (MDC1A) has received little clinical attention. This study aimed to present pathological changes in intramuscular nerves of three patients with MDC1A and discuss their relationship with electrophysiological findings to provide new evidence of peripheral nerve involvement in MDC1A.
METHODS
MDC1A was confirmed by clinical features, muscle biopsy, and genetic testing for variants in LAMA2. To clarify peripheral nerve involvement, we statistically evaluated electrophysiological and muscle pathology findings of intramuscular nerves. These findings were compared with those of age-matched boys with Duchenne muscular dystrophy (DMD) as controls with normal nerves. Nerve conduction studies (NCS) were performed before biopsy. Biopsied intramuscular nerves were examined with electron microscopy using g-ratio, which is the ratio of axon diameter to myelinated fiber diameter.
RESULTS
The myelin sheaths were significantly thinner in MDC1A patients than in age-matched DMD patients, with a mean g-ratio of 0.76 ± 0.07 in MDC1A patients and 0.65 ± 0.14 in DMD patients (p < .0001). No neuropathic changes were identified in muscle pathology. Low compound muscle action potential amplitudes, positive sharp waves and fibrillation potentials, and low-amplitude motor unit potentials with increased polyphasia indicated myopathic changes; no neurogenic changes were seen.
DISCUSSION
We postulate that the thin myelin associated with MDC1A reflects the role of merosin in myelin maturation.
Topics: Male; Humans; Myelin Sheath; Muscle, Skeletal; Laminin; Muscular Dystrophy, Duchenne; Peripheral Nervous System Diseases
PubMed: 37933889
DOI: 10.1002/mus.28002 -
International Journal of Molecular... Dec 2023Exosomes are nanoscale-sized membrane vesicles released by cells into their extracellular milieu. Within these nanovesicles reside a multitude of bioactive molecules,... (Review)
Review
Exosomes are nanoscale-sized membrane vesicles released by cells into their extracellular milieu. Within these nanovesicles reside a multitude of bioactive molecules, which orchestrate essential biological processes, including cell differentiation, proliferation, and survival, in the recipient cells. These bioactive properties of exosomes render them a promising choice for therapeutic use in the realm of tissue regeneration and repair. Exosomes possess notable positive attributes, including a high bioavailability, inherent safety, and stability, as well as the capacity to be functionalized so that drugs or biological agents can be encapsulated within them or to have their surface modified with ligands and receptors to imbue them with selective cell or tissue targeting. Remarkably, their small size and capacity for receptor-mediated transcytosis enable exosomes to cross the blood-brain barrier (BBB) and access the central nervous system (CNS). Unlike cell-based therapies, exosomes present fewer ethical constraints in their collection and direct use as a therapeutic approach in the human body. These advantageous qualities underscore the vast potential of exosomes as a treatment option for neurological injuries and diseases, setting them apart from other cell-based biological agents. Considering the therapeutic potential of exosomes, the current review seeks to specifically examine an area of investigation that encompasses the development of Schwann cell (SC)-derived exosomal vesicles (SCEVs) as an approach to spinal cord injury (SCI) protection and repair. SCs, the myelinating glia of the peripheral nervous system, have a long history of demonstrated benefit in repair of the injured spinal cord and peripheral nerves when transplanted, including their recent advancement to clinical investigations for feasibility and safety in humans. This review delves into the potential of utilizing SCEVs as a therapy for SCI, explores promising engineering strategies to customize SCEVs for specific actions, and examines how SCEVs may offer unique clinical advantages over SC transplantation for repair of the injured spinal cord.
Topics: Humans; Spinal Cord; Spinal Cord Injuries; Schwann Cells; Peripheral Nerves; Neuroglia; Exosomes
PubMed: 38139147
DOI: 10.3390/ijms242417317 -
Journal of Materials Chemistry. B Feb 2024During the process of peripheral nerve repair, there are many complex pathological and physiological changes, including multi-cellular responses and various signaling... (Review)
Review
During the process of peripheral nerve repair, there are many complex pathological and physiological changes, including multi-cellular responses and various signaling molecules, and all these events establish a dynamic microenvironment for axon repair, regeneration, and target tissue/organ reinnervation. The immune system plays an indispensable role in the process of nerve repair and function recovery. An effective immune response not only involves innate-immune and adaptive-immune cells but also consists of chemokines and cytokines released by these immune cells. The elucidation of the orchestrated interplay of immune cells with nerve regeneration and functional restoration is meaningful for the exploration of therapeutic strategies. This review mainly enumerates the general immune cell response to peripheral nerve injury and focuses on their contributions to functional recovery. The tissue engineering-mediated strategies to regulate macrophages and T cells through physical and biochemical factors combined with scaffolds are discussed. The dynamic immune responses during peripheral nerve repair and immune-cell-mediated tissue engineering methods are presented, which provide a new insight and inspiration for immunomodulatory therapies in peripheral nerve regeneration.
Topics: Humans; Peripheral Nerve Injuries; Tissue Engineering; Peripheral Nerves; Nerve Regeneration; Macrophages
PubMed: 38345580
DOI: 10.1039/d3tb02557h -
European Journal of Anaesthesiology Sep 2023Liposomal bupivacaine is claimed by the manufacturer to provide analgesia for up to 72 h postoperatively. (Meta-Analysis)
Meta-Analysis
The postoperative analgesic efficacy of liposomal bupivacaine versus long-acting local anaesthetics for peripheral nerve and field blocks: A systematic review and meta-analysis, with trial sequential analysis.
BACKGROUND
Liposomal bupivacaine is claimed by the manufacturer to provide analgesia for up to 72 h postoperatively.
OBJECTIVES
To compare the postoperative analgesic efficacy of liposomal bupivacaine versus long-acting local anaesthetics for peripheral nerve or field blocks.
DESIGN
A systematic review and meta-analysis with trial sequential analysis.
DATA SOURCES
MEDLINE, Embase and Web of Science, among others, up to June 2022.
ELIGIBILITY CRITERIA
We retrieved randomised controlled trials comparing liposomal bupivacaine versus bupivacaine, levobupivacaine or ropivacaine for peripheral nerve and field blocks after all types of surgery. Our primary endpoint was rest pain score (analogue scale 0 to 10) at 24 h. Secondary endpoints included rest pain score at 48 and 72 h, and morphine consumption at 24, 48 and 72 h.
RESULTS
Twenty-seven trials including 2122 patients were identified. Rest pain scores at 24 h were significantly reduced by liposomal bupivacaine with a mean difference (95% CI) of -0.9 (-1.4 to -0.4), I2 = 87%, P < 0.001. This reduction in pain scores persisted at 48 h and 72 h with mean differences (95% CI) of -0.7 (-1.1 to -0.3), I2 = 82%, P = 0.001 and -0.7 (-1.1 to -0.3), I2 = 80%, P < 0.001, respectively. There were no differences in interval morphine consumption at 24 h ( P = 0.15), 48 h ( P = 0.15) and 72 h ( P = 0.07). The quality of evidence was moderate.
CONCLUSIONS
There is moderate level evidence that liposomal bupivacaine reduces rest pain scores by 0.9 out of 10 units, when compared with long-acting local anaesthetics at 24 hours after surgery, and by 0.7 up to 72 hours after surgery.
Topics: Humans; Anesthetics, Local; Pain, Postoperative; Bupivacaine; Analgesics; Morphine; Peripheral Nerves; Analgesics, Opioid
PubMed: 37038770
DOI: 10.1097/EJA.0000000000001833 -
Journal of Reconstructive Microsurgery May 2024Cryoanalgesia is a tool being used by interventional radiology to treat chronic pain. Within a certain cold temperature range, peripheral nerve function is... (Review)
Review
BACKGROUND
Cryoanalgesia is a tool being used by interventional radiology to treat chronic pain. Within a certain cold temperature range, peripheral nerve function is interrupted and recovers, without neuroma formation. Cryoanalgesia has most often been applied to the intercostal nerve. Cryoanalgesia has applications to peripheral nerve surgery, yet is poorly understood by reconstructive microsurgeons.
METHODS
Histopathology of nerve injury was reviewed to understand cold applied to peripheral nerve. Literature review was performed utilizing the PubMed and MEDLINE databases to identify comparative studies of the efficacy of intraoperative cryoanalgesia versus thoracic epidural anesthesia following thoracotomy. Data were analyzed using Fisher's exact and analysis of variance tests. A similar approach was used for pudendal cryoanalgesia.
RESULTS
Application of inclusion and exclusion criteria resulted in 16 comparative clinical studies of intercostal nerve for this review. For thoracotomy, nine studies compared cryoanalgesia with pharmaceutical analgesia, with seven demonstrating significant reduction in postoperative opioid use or postoperative acute pain scores. In these nine studies, there was no association between the number of nerves treated and the reduction in acute postoperative pain. One study compared cryoanalgesia with local anesthetic and demonstrated a significant reduction in acute pain with cryoanalgesia. Three studies compared cryoanalgesia with epidural analgesia and demonstrated no significant difference in postoperative pain or postoperative opioid use. Interventional radiology targets pudendal nerves using computed tomography imaging with positive outcomes for the patient with pain of pudendal nerve origin.
CONCLUSION
Cryoanalgesia is a term used for the treatment of peripheral nerve problems that would benefit from a proverbial reset of peripheral nerve function. It does not ablate the nerve. Intraoperative cryoanalgesia to intercostal nerves is a safe and effective means of postoperative analgesia following thoracotomy. For pudendal nerve injury, where an intrapelvic surgical approach may be difficult, cryoanalgesia may provide sufficient clinical relief, thereby preserving pudendal nerve function.
Topics: Humans; Analgesics, Opioid; Acute Pain; Cryotherapy; Analgesia; Pain, Postoperative; Intercostal Nerves
PubMed: 37751885
DOI: 10.1055/a-2182-1198 -
Journal of Neural Engineering Aug 2023A transverse intrafascicular multichannel electrode (TIME) may offer advantages over more conventional cuff electrodes including higher spatial selectivity and reduced...
A transverse intrafascicular multichannel electrode (TIME) may offer advantages over more conventional cuff electrodes including higher spatial selectivity and reduced stimulation charge requirements. However, the performance of TIME, especially in the context of non-conventional stimulation waveforms, remains relatively unexplored. As part of our overarching goal of investigating stimulation efficacy of TIME, we developed a computational toolkit that automates the creation and usage ofnerve models with TIME setup, which solves nerve responses using cable equations and computes extracellular potentials using finite element method.We began by implementing a flexible and scalable Python/MATLAB-based toolkit for automatically creating models of nerve stimulation in the hybrid NEURON/COMSOL ecosystems. We then developed a sciatic nerve model containing 14 fascicles with 1,170 myelinated (A-type, 30%) and unmyelinated (C-type, 70%) fibers to study fiber responses over a variety of TIME arrangements (monopolar and hexapolar) and stimulation waveforms (kilohertz stimulation and cathodic ramp modulation).Our toolkit obviates the conventional need to re-create the same nerve in two disparate modeling environments and automates bi-directional transfer of results. Our population-based simulations suggested that kilohertz stimuli provide selective activation of targeted C fibers near the stimulating electrodes but also tended to activate non-targeted A fibers further away. However, C fiber selectivity can be enhanced by hexapolar TIME arrangements that confined the spatial extent of electrical stimuli. Improved upon prior findings, we devised a high-frequency waveform that incorporates cathodic DC ramp to completely remove undesirable onset responses.Our toolkit allows agile, iterative design cycles involving the nerve and TIME, while minimizing the potential operator errors during complex simulation. The nerve model created by our toolkit allowed us to study and optimize the design of next-generation intrafascicular implants for improved spatial and fiber-type selectivity.
Topics: Ecosystem; Peripheral Nerves; Electrodes; Axons; Sciatic Nerve; Myelin Sheath; Electric Stimulation; Electrodes, Implanted
PubMed: 37536318
DOI: 10.1088/1741-2552/aced20 -
Journal of Translational Medicine Aug 2023Brachial plexus root avulsion (BPRA), a disabling peripheral nerve injury, induces substantial motoneuron death, motor axon degeneration and denervation of biceps...
BACKGROUND
Brachial plexus root avulsion (BPRA), a disabling peripheral nerve injury, induces substantial motoneuron death, motor axon degeneration and denervation of biceps muscles, leading to the loss of upper limb motor function. Acetylglutamine (N-acetyl-L-glutamine, NAG) has been proven to exert neuroprotective and anti-inflammatory effects on various disorders of the nervous system. Thus, the present study mainly focused on the influence of NAG on motor and sensory recovery after BPRA in rats and the underlying mechanisms.
METHODS
Male adult Sprague Dawley (SD) rats were subjected to BPRA and reimplantation surgery and subsequently treated with NAG or saline. Behavioral tests were conducted to evaluate motor function recovery and the mechanical pain threshold of the affected forelimb. The morphological appearance of the spinal cord, musculocutaneous nerve, and biceps brachii was assessed by histological staining. Quantitative real-time PCR (qRT‒PCR) was used to measure the mRNA levels of remyelination and regeneration indicators in myocutaneous nerves. The protein levels of inflammatory and pyroptotic indicators in the spinal cord anterior horn were measured using Western blotting.
RESULTS
NAG significantly accelerated the recovery of motor function in the injured forelimbs, enhanced motoneuronal survival in the anterior horn of the spinal cord, inhibited the expression of proinflammatory cytokines and pyroptosis pathway factors, facilitated axonal remyelination in the myocutaneous nerve and alleviated atrophy of the biceps brachii. Additionally, NAG attenuated neuropathic pain following BPRA.
CONCLUSION
NAG promotes functional motor recovery and alleviates neuropathic pain by enhancing motoneuronal survival and axonal remyelination and inhibiting the pyroptosis pathway after BPRA in rats, laying the foundation for the use of NAG as a novel treatment for BPRA.
Topics: Male; Rats; Animals; Rats, Sprague-Dawley; Neuralgia; Spinal Cord; Atrophy; Brachial Plexus
PubMed: 37612586
DOI: 10.1186/s12967-023-04399-7