Nerve Research Articles

Upper Extremity Ballistic Nerve Injury

» Gunshot injuries to the upper extremity (UE) have high likelihood for causing peripheral nerve injury secondary to the high density of vital structures. Roughly one-fourth of patients sustaining a gunshot wound (GSW) to the UE incur a nerve injury. Of these nerve injuries, just over half are neurapraxic. In cases of surgical exploration of UE nerve injuries, nearly one-third demonstrate a transected or discontinuous nerve.» Existing literature regarding surgical management of nerve injuries secondary to GSWs comes from both military and civilian injuries. Outcomes are inconsistently reported, and indications are heterogeneous; however, reasonable results can be obtained with nerve reconstruction.» Our proposed management algorithm hinges on 4 treatment questions: if there is a nerve deficit present on examination, if there is a concomitant injury in the extremity (i.e., fracture or vascular insult), whether the injured nerve would be in the operative field of the concomitant injury, and whether there was an identified nerve lesion encountered at the time of surgery by another surgeon?» Early exploration rather than continued expectant management may offer improved recovery from GSW nerve injuries in particular situations. When an UE nerve deficit is present, establishing follow-up after the initial GSW encounter and early referral to a peripheral nerve surgeon are pivotal.

Wireless Optogenetic Targeting Nociceptors Helps Host Cells Win the Competitive Colonization in Implant-Associated Infections.

The role of nociceptive nerves in modulating immune responses to harmful stimuli via pain or itch induction remains controversial. Compared to conventional surgery, various implant surgeries are more prone to infections even with low bacterial loads. In this study, an optogenetic technique is introduced for selectively activating peripheral nociceptive nerves using a fully implantable, wirelessly rechargeable optogenetic device. By targeting nociceptors in the limbs of awake, freely moving mice, it is found that activation induces anticipatory immunity in the innervated territory and enhances the adhesion of various host cells to the implant surface. This effect mediates acute immune cell-mediated killing of Staphylococcus aureus on implants and enables the host to win "implant surface competition" against Staphylococcus aureus. This finding provides new strategies for preventing and treating implant-associated infections.

Early Peripheral Nerve Involvement at the Time of Coughing in Patients With RFC1 Intronic Expansion

Early Peripheral Nerve Involvement at the Time of Coughing in Patients With <i>RFC1</i> Intronic Expansion

Association between postoperative shoulder pain and left-side laparoscopic urologic surgery: a single-center retrospective cohort study.

Postoperative shoulder pain is a common problem after laparoscopic surgery. This study aimed to investigate the association between operative side and postoperative shoulder pain following urologic laparoscopic surgery performed in the lateral recumbent position. This was a retrospective cohort study conducted at a single tertiary care center. A total of 506 patients who underwent urologic laparoscopic surgery (including adrenalectomy, radical nephrectomy, partial nephrectomy, and pyeloplasty) between January 2010 and December 2019 were included. Patients who underwent total nephroureterectomy or resection of other organs were excluded. The primary outcome was the incidence of postoperative shoulder pain. A multivariable logistic regression analysis investigated the association between the operative side and postoperative shoulder pain. Among the 506 included patients, there were an equal number of surgeries on the left and right sides. Eighty-eight patients had postoperative shoulder pain. The incidence of postoperative shoulder pain in the left-side group was significantly higher than that in the right-side group (21.3% [54/253] versus 13.4% [34/253], crude odds ratio = 1.75, 95% confidence interval [CI] 1.07-2.89). After adjustment for potential confounders (age, sex, body mass index, operation duration, operative technique, epidural block, peripheral nerve block, American Society of Anesthesiologists physical status classification, and intraoperative rocuronium dose), the left operative side was found to be associated with postoperative shoulder pain (adjusted odds ratio = 1.89, 95% CI 1.15-3.09). The left operative side is associated with an increased incidence of postoperative shoulder pain after urologic laparoscopic surgery performed in the lateral recumbent position.

Peripheral and central pathogenesis of postherpetic neuralgia.

Postherpetic neuralgia (PHN) is a classic chronic condition with multiple signs of peripheral and central neuropathy. Unfortunately, the pathogenesis of PHN is not well defined, limiting clinical treatment and disease management. To describe the peripheral and central pathological axes of PHN, including peripheral nerve injury, inflammation induction, central nervous system sensitization, and brain functional and structural network activity. A bibliographic survey was carried out, selecting relevant articles that evaluated the characterization of the pathogenesis of PHN, including peripheral and central pathological axes. Currently, due to the complexity of the pathophysiological mechanisms of PHN and the incomplete understanding of the exact mechanism of neuralgia. It is essential to conduct in-depth research to clarify the origins of PHN pathogenesis and explore effective and comprehensive therapies for PHN.

Investigating therapeutic nonsense suppression in a neurofibromatosis mouse model

Neurofibromatosis type 1 (NF1) is a human genetic disorder caused by variants in the NF1 gene. Plexiform neurofibromas, one of many NF1 manifestations, are benign peripheral nerve sheath tumors occurring in up to 50% of NF1 patients. A substantial fraction of NF1 pathogenetic variants are nonsense mutations, which result in the synthesis of truncated non-functional NF1 protein (neurofibromin). To date, no therapeutics have restored neurofibromin expression or addressed the consequences of this protein's absence in NF1 nonsense mutation patients, but nonsense suppression is a potential approach to the problem. Ataluren is a small molecule drug that has been shown to stimulate functional nonsense codon readthrough in several models of nonsense mutation diseases, as well as in Duchenne muscular dystrophy patients. To test ataluren's potential applicability in nonsense mutation NF1 patients, we evaluated its therapeutic effects using three treatment regimens in a previously established NF1 patient-derived (c.2041C > T; p.Arg681X) nonsense mutation mouse model. Collectively, our experiments indicate that: i) ataluren appeared to slow the growth of neurofibromas and alleviate some paralysis phenotypes, ii) female Nf1-nonsense mutation mice manifested more severe paralysis and neurofibroma phenotypes than male mice, iii) ataluren doses with apparent effectiveness were lower in female mice than in male mice, and iv) age factors also influenced ataluren's effectiveness.

Interleukin-35 alleviates neuropathic pain and induces an anti-inflammatory shift in spinal microglia in nerve-injured male mice

Immune cells are critical in promoting neuroinflammation and neuropathic pain and in facilitating pain resolution, depending on their inflammatory and immunoregulatory cytokine response. Interleukin (IL)-35, secreted by regulatory immune cells, is a member of the IL-12 family with a potent immunosuppressive function. In this study, we investigated the effects of IL-35 on pain behaviors, spinal microglia phenotype following peripheral nerve injury, and in vitro microglial cultures in male and female mice. Intrathecal recombinant IL-35 treatment alleviated mechanical pain hypersensitivity prominently in male mice, with only a modest effect in female mice after sciatic nerve chronic constriction injury (CCI). IL-35 treatment resulted in sex-specific microglial changes following CCI, reducing inflammatory microglial markers and upregulating anti-inflammatory markers in male mice. Spatial transcriptomics analysis revealed that IL-35 suppressed microglial complement activation in the superficial dorsal horn in male mice after CCI. Moreover, in vitro studies showed that IL-35 treatment of cultured inflammatory microglia mitigated their hypertrophied morphology, increased their cell motility, and decreased their phagocytic activity, indicating a phenotypic shift towards homeostatic microglia. Further, IL-35 altered microglial cytokines/chemokines in vitro, suppressing the release of IL-9 and monocyte-chemoattractant protein-1 and increasing IL-10 in the supernatant of male microglial cultures. Our findings indicate that treatment with IL-35 modulates spinal microglia and alleviates neuropathic pain in male mice, suggesting IL-35 as a potential sex-specific targeted immunomodulatory treatment for neuropathic pain.

PLCL/SF/NGF nerve conduit loaded with RGD-TA-PPY hydrogel promotes regeneration of sciatic nerve defects in rats through PI3K/AKT signalling pathways.

Peripheral nerve defect are common clinical problem caused by trauma or other diseases, often leading to the loss of sensory and motor function in patients. Autologous nerve transplantation has been the gold standard for repairing peripheral nerve defects, but its clinical application is limited due to insufficient donor tissue. In recent years, the application of tissue engineering methods to synthesize nerve conduits for treating peripheral nerve defect has become a current research focus. This study introduces a novel approach for treating peripheral nerve defects using a tissue-engineered PLCL/SF/NGF@TA-PPy-RGD conduit. The conduit was fabricated by combining electrospun PLCL/SF with an NGF-loaded conductive TA-PPy-RGD gel. The gel, synthesized from RGD-modified tannic acid (TA) and polypyrrole (PPy), provides growth anchor points for nerve cells. Invitro results showed that this hybrid conduit could enhance PC12 cell proliferation, migration, and reduce apoptosis under oxidative stress. Furthermore, the conduit activated the PI3K/AKT signalling pathway in PC12 cells. In a rat model of sciatic nerve defect, the PLCL/SF/NGF@TA-PPy-RGD conduit significantly improved motor function, gastrocnemius muscle function, and myelin sheath axon thickness, comparable to autologous nerve transplantation. It also promoted angiogenesis around the nerve defect. This study suggests that PLCL/SF/NGF@TA-PPy-RGD conduits provide a conducive environment for nerve regeneration, offering a new strategy for peripheral nerve defect treatment, this study provided theoretical basis and new strategies for the research and treatment of peripheral nerve defect.

Age related changes in skin sensitivity assessed with smartphone vibration testing

The capacity to perceive tactile input at the fingertips, referred to as tactile sensitivity, is known to diminish with age due to regressive changes to mechanoreceptor density and morphology. Sensitivity is measured as perceptual responses to stimuli of varying intensity. Contrary to traditional sensitivity monitoring instruments, smartphones are uniquely suited for remote assessment and have shown to deliver highly calibrated stimuli along a broad spectrum of intensity, which may improve test reliability. The aim of this study was to evaluate a vibration-emitting smartphone application, the Vibratus App, as a mode of estimating tactile sensory thresholds in the aging adult. The peripheral nerve function of 40 neurologically healthy volunteers (ages 18–71) was measured using monofilaments, a 128-Hz tuning fork, the Vibratus App, and nerve conduction studies (NCS). Between group differences were analyzed to determine each measurement’s sensitivity to age. Spearman correlation coefficients depicted the associative strength between hand-held measurements and sensory nerve action potential (SNAP) amplitude. Inter-rater reliability of traditional instruments and the software-operated smartphone were assessed by intraclass correlation coefficient (ICC2,k). Measurements taken with Vibratus App were significantly different between age groups (p < 0.001). The inter-rater reliability of monofilament, smartphone vibration, and tuning fork testing was moderate to good (ICC2,k = 0.65, 0.69, and 0.79, respectively). The findings of this study support further investigation of smartphones as sensitivity monitoring devices for at home monitoring of skin sensitivity.

Incidence and predictive factors of double crush syndrome in patients undergoing cervical surgery: a database study.

Double crush syndrome (DCS) is characterized by multiple compression sites along a single peripheral nerve. It commonly presents with persistent distal symptoms despite surgical treatment for cervical radiculopathy. Management typically involves nerve release of the most symptomatic site. However, due to overlapping symptoms with cervical radiculopathy, patients may undergo cervical surgery prior to DCS diagnosis. Due to its rarity and frequent misdiagnosis, the authors aim to utilize a large national database to investigate the incidence and associations of DCS. The Pearldiver database was utilized to identify patients undergoing cervical surgery for the management of cervical radiculopathy. Patients were stratified into three cohorts based on their clinical course before and after cervical surgery. The primary outcome was the prevalence of DCS, and secondary outcomes included an evaluation of predictive factors for each Group, using a significance level of P < 0.05. Among 195,271 patients undergoing cervical surgery for cervical radiculomyelopathy, 97.95% were appropriately managed, 1.42% had potentially mids-diagnosed DCS, and 0.63% were treatment-resistant. Diabetes and obesity were significant predictors of potentially misdiagnosed DCS (P < 0.05). This study presents data indicating that 1.42% of patients who receive cervical surgery may have underlying DCS and potentially benefit from nerve release prior to undergoing surgery. A concurrent diagnosis of diabetes and obesity may predict an underlying DCS.

Vitamin D Deficiency as a Factor Associated with Neuropathic Pain in Multibacillary Type Morbus Hansen

Objective: Morbus Hansen (MH), caused by Mycobacterium leprae, is marked by neuropathic pain. Prior studies link low vitamin D levels to diabetic neuropathic pain, yet research on its role in MH-related neuropathic pain is limited. This study investigates the role of vitamin D deficiency in MH-related neuropathic pain. Materials and Methods: An analytical cross-sectional study was conducted among multibacillary (MB) MH patients at Prof. Dr. I.G.N.G. Ngoerah Hospital, Bali from April to August 2023. Neuropathic pain was assessed using the Douleur Neuropathique 4 (DN4) questionnaire, while serum 25(OH)D levels determined vitamin D status. The cutoff for deficiency was determined via ROC curve analysis. Results: Among 42 participants, those without neuropathic pain exhibited higher mean serum vitamin D levels than those with neuropathic pain (28.69 ± 8.16 vs. 22.11 ± 9.54 ng/ml; p=0.021). The ROC curve identified a cutoff value of 30.25 ng/ml, categorizing participants into vitamin D deficiency (&lt;30.25 ng/ml) and non-deficiency (≥30.25 ng/ml) groups. Bivariate analysis revealed a heightened incidence of neuropathic pain among MH patients with serum vitamin D levels below the designated cutoff point (OR: 6.60; 95%CI: 1.484-29.355; p=0.022). Multivariate analysis indicated that two variables significantly correlated with neuropathic pain in MH patients: vitamin D deficiency (OR: 14.337; 95%CI: 2.431-84.542; p=0.003) and peripheral nerve enlargement (OR: 12.564; 95%CI: 2.096-75.307; p=0.006). Conclusion: Disparities in average vitamin D levels were observed between MH patients with and without neuropathic pain. Vitamin D deficiency, alongside peripheral nerve enlargement, emerged as significant risk factors for neuropathic pain in MH patients.

Innovations in the classification of soft tissue tumors

Soft tissue tumors are avery heterogeneous group of tumors. Their classification is regularly updated by the World Health Organization (WHO), most recently in 2020. The current classification of soft tissue tumors emphasizes molecular biological tumor characteristics, which enable tumor-specific treatment. In addition to Ewing's sarcoma, which occurs as bone as well as extra-skeletal soft tissue tumors as asmall round cell sarcoma, three other subtypes of undifferentiated, small and round cell sarcomas have been introduced. Some names of the new sarcomas can be derived from the gene mutations. The groups of adipocytic and (myo)fibroblastic tumors have been extended by three further entities. There were further additions to vascular soft tissue tumors, smooth muscle cell tumors, peripheral nerve sheath tumors and tumors of uncertain differentiation. Adistinction is made between benign, intermediate locally aggressive, intermediate rarely metastatic and malignant soft tissue tumors.

Biohacking Nerve Repair: Novel Biomaterials, Local Drug Delivery, Electrical Stimulation, and Allografts to Aid Surgical Repair

The regenerative capacity of the peripheral nervous system is limited, and peripheral nerve injuries often result in incomplete healing and poor outcomes even after repair. Transection injuries that induce a nerve gap necessitate microsurgical intervention; however, even the current gold standard of repair, autologous nerve graft, frequently results in poor functional recovery. Several interventions have been developed to augment the surgical repair of peripheral nerves, and the application of functional biomaterials, local delivery of bioactive substances, electrical stimulation, and allografts are among the most promising approaches to enhance innate healing across a nerve gap. Biocompatible polymers with optimized degradation rates, topographic features, and other functions provided by their composition have been incorporated into novel nerve conduits (NCs). Many of these allow for the delivery of drugs, neurotrophic factors, and whole cells locally to nerve repair sites, mitigating adverse effects that limit their systemic use. The electrical stimulation of repaired nerves in the perioperative period has shown benefits to healing and recovery in human trials, and novel biomaterials to enhance these effects show promise in preclinical models. The use of acellular nerve allografts (ANAs) circumvents the morbidity of donor nerve harvest necessitated by the use of autografts, and improvements in tissue-processing techniques may allow for more readily available and cost-effective options. Each of these interventions aid in neural regeneration after repair when applied independently, and their differing forms, benefits, and methods of application present ample opportunity for synergistic effects when applied in combination.

Comparison of curved and straight tip radiofrequency cannula deflection in a ballistic model

BackgroundPercutaneous pain and spine procedures play an important diagnostic and therapeutic role in the treatment of various pain diagnoses. Accurate placement of needles or cannulae during these procedures is paramount to the success of these procedures. ObjectiveThe purpose of this study is to examine and quantify the amount of deflection of radiofrequency cannulae based on curved tip versus no curved tip, using a ballistic gel tissue simulant. Materials and methodsSix different types of cannulae commonly used for spinal and peripheral nerve ablations were selected, including 18, 20, and 22 gauge curved and straight radiofrequency cannulae. Ballistic gel samples were made in molds of 40 mm and 80 mm. Each cannula was mounted in a drill press to ensure accurate trajectory. ResultsCurved RFA cannula had increased deflection when compared to straight cannula for 18-, 20-, and 22-gauge cannulae at a depth of 40 mm. Curved RFA cannula had increased deflection when compared to straight cannula for 20- and 22-gauge cannulae at a depth of 80 mm. Overall, the mean deflection for a curved cannula increased 1.9x for 20-gauge cannulae and 2.5x for 22-gauge cannulae when compared to a straight cannula. ConclusionsFor interventionalists, understanding the effects of needle or cannula shape is crucial for accurate placement. When a procedure requires additional steerability, additional deflection up to 2.5x obtained by placing a bend in the needle or cannula tip should be considered.

The use of pre-emptive percutaneous cryoanalgesia beforemodified Ravitch funnel chest surgery – a new form ofpostoperative pain management. A report of two clinical cases

Pectus excavatum (PE) is the most common congenital deformity of the anterior chest wall, with an estimatedincidence of 1 in 400–1000 births. It typically manifests in the neonatal period but can also appear duringadolescence. Clinical symptoms may arise from compression of the lungs and heart. The standard treatment forPE is surgical intervention. The modified Ravitch procedure is an invasive correction method used to treat pectusexcavatum. This procedure is associated with significant postoperative pain, often exceeding 5 on the numericalrating scale (NRS), which can be difficult to manage with conventional methods such as patient-controlled analgesia(PCA) or continuous thoracic epidural analgesia (cTE). A new alternative adjunct therapy for managing acutepain after thoracic surgery is peripheral nerves cryoablation – a procedure involving temporary blockade of nerveconduction in the intercostal nerves using a narrow range of low temperatures, optimally performed before thesurgical procedure. This results in long-lasting analgesia that allows for a reduction of opioid requirements or evencomplete discontinuation. This paper presents two cases of pediatric patients who, due to invasive thoracic surgicalprocedures, underwent intercostal percutaneous cryoablation (IPC) before the surgery. Performing preemptivepercutaneous intercostal nerve cryoablation reduced opioid intake and allowed for shorter hospital stay, as well assignificantly increased comfort of our patients. The description of these two cases aims to highlight the preemptivecryoablation as a potential, potent, alternative analgesia method adjunct to pharmacotherapy of pain in patientsundergoing extensive thoracic surgical procedures.

Multilevel neurium-mimetic individualized graft via additive manufacturing for efficient tissue repair

Complicated peripheral nerve injuries or defects, especially at branching sites, remain a prominent clinical challenge after the application of different treatment strategies. Current nerve grafts fail to match the expected shape and size for delicate and precise branched nerve repair on a case-by-case basis, and there is a lack of geometrical and microscale regenerative navigation. In this study, we develop a sugar painting-inspired individualized multilevel epi-/peri-/endoneurium-mimetic device (SpinMed) to customize natural cues, featuring a selectively protective outer sheath and an instructive core, to support rapid vascular reconstruction and consequent efficient neurite extension along the defect area. The biomimetic perineurium dictates host-guest crosslinking in which new vessels secrete multimerin 1 binding to the fibroin filler surface as an anchor, contributing to the biological endoneurium that promotes Schwann cell homing and remyelination. SpinMed implantation into rat sciatic nerve defects yields a satisfactory outcome in terms of structural reconstruction, with sensory and locomotive function restoration. We further customize SpinMed grafts based on anatomy and digital imaging, achieving rapid repair of the nerve trunk and branches superior to that achieved by autografts and decellularized grafts in a specific beagle nerve defect model, with reliable biosafety. Overall, this intelligent art-inspired biomimetic design offers a facile way to customize sophisticated high-performance nerve grafts and holds great potential for application in translational regenerative medicine.

Review on potential nerve guidance conduits design for spinal cord injuries

The current treatment of spinal cord injuries (SCI) focuses mainly on the elimination of secondary damage to the central nervous system. The performance of treatments targeted at neurological recovery is not satisfactory. Inspired by the treatment of peripheral nerve injuries using tissue engineering, the nerve guidance conduits became one of the potential designs to improve the rate of neurological recovery among patients. With the proper design like multichannel and fabrication techniques like 3D bioprinting, the hybrid biomaterial may provide good guidance for nerves to grow in long gaps under well-picked neuromorphic factors. The new technologies including vascularization and electrical stimulation give more possibilities for the construction of treatment. New materials like shape-memory polymers may improve the fabrication of NGCs. However, the combination of these innovative findings was not performed for lab tests and clinical tests. The commercialization of NGC for SCI is also in need of better standardization and regulation. There may be a comprehensive NGC-based design for SCI emerging in the future which improves the performance of neurological recovery.

The possibilities of ultrasound examination in the diagnosis of joint and peripheral nerve damage in vibration disease: a review of the literature

The possibilities of ultrasound examination in the diagnosis of joint and peripheral nerve damage in vibration disease: a review of the literature

Characteristics of after-discharges following compound muscle action potential or F-wave in primary peripheral nerve hyperexcitability syndrome.

F-wave testing frequently reveals after-discharges of varied morphologies in patients with primary peripheral nerve hyperexcitability syndrome (PNHS), although reports are scant. This study aimed to explore the morphological characteristics of the after-discharges during F-wave tests in PNHS, and to assess the association between after-discharges and the disease classification. We conducted a retrospective analysis of patients diagnosed with PNHS between 2014 and 2022. The morphological characteristic and duration of after-discharges during F-wave tests were analyzed. After-discharges in the Morvan syndrome group were compared with those in non-Morvan group, and between groups with positive or negative voltage-gated potassium channel (VGKC) complex antibodies. Twenty-nine patients were included in the study, of which 25 exhibited after-discharges. All after-discharges in Morvan patients occurred following compound muscle action potential (CMAP). In non-Morvan patients, after-discharges occurred following F-wave (32%) and CMAP (47%). The durations of after-discharges following CMAP were significantly prolonged in Morvan (54.2 ± 18.8 ms) compared to non-Morvan patients (34.5 ± 15.0 ms). The majority of antibody-positive patients (18/20) exhibited after-discharges following CMAP, whereas 67% of antibody-negative patients (6/9) showed after-discharges following F-wave. The varying presentations of after-discharges, including their location (after CMAP or F-wave) and the duration of after-discharge can assist in clinically classifying PNHS.

Navigating Preclinical Models and Medications for Peripheral Neuropathy: A Review

Peripheral neuropathy (PN) is a multifaceted disorder characterised by peripheral nerve damage, manifesting in symptoms like pain, weakness, and autonomic dysfunction. This review assesses preclinical models in PN research, evaluating their relevance to human disease and their role in therapeutic development. The Streptozotocin (STZ)-induced diabetic rat model is widely used to simulate diabetic neuropathy but has limitations in faithfully replicating disease onset and progression. Cisplatin-induced PN models are suitable for studying chemotherapy-induced peripheral neuropathy (CIPN) and closely resemble human pathology. However, they may not fully replicate the spectrum of sensory and motor deficits. Paclitaxel-induced models also contribute to understanding CIPN mechanisms and testing neuroprotective agents. Surgical or trauma-induced models offer insights into nerve regeneration and repair strategies. Medications such as gabapentin, pregabalin, duloxetine, and fluoxetine have demonstrated promise in these models, enhancing our understanding of their therapeutic efficacy. Despite progress, developing models that accurately mirror human PN remains imperative due to its complex nature. Continuous refinement and innovative approaches are critical for effective drug discovery. This review underscores the strengths and limitations of current models and advocates for an integrated approach to address the complexities of PN better and optimise treatment outcomes.