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The successful removal of damaged myelin sheaths during Wallerian degeneration (WD) is essential for ensuring structural remodelling and functional recovery following traumatic peripheral nerve injury (PNI). Recent studies have established that autophagy involves myelin phagocytosis and cellular homoeostasis, and its disorder impairs myelin clearance. Based on the role of basic fibroblast growth factor (bFGF) on exerting neuroprotection and angiogenesis during nerve tissue regeneration, we now explicitly focus on the issue about whether the therapeutic effect of bFGF on supporting nerve regeneration is closely related to accelerate the autophagic clearance of myelin debris during WD. Using sciatic nerve crushed model, we found that bFGF remarkedly improved axonal outgrowth and nerve reconstruction at the early phase of PNI (14 days after PNI). More importantly, we further observed that bFGF could enhance phagocytic capacity of Schwann cells (SCs) to engulf myelin debris. Additionally, this enhancing effect is accomplished by autophagy activation and the increase of autophagy flux by immunoblotting and immune-histochemical analyses. Taken together, our data suggest that the action of bFGF on modulating early peripheral nerve regeneration is closely associated with myelin debris removal by SCs, which might result in SC-mediated autophagy activation, highlighting its insight molecular mechanism as a neuroprotective agent for repairing PNI., (© 2021 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.)

The common neurotrophin receptor, p75 NTR , has been proposed to be an inhibitor of axon regeneration after peripheral nerve injury, but whether this effect is on the regenerating axons, immune cells migrating into the injury site, or cells in the pathway surrounding the axons is not clear. Cut nerves in mice expressing fluorescent proteins in axons were repaired with grafts from non-fluorescent hosts to study axon elongation when p75 NTR was eliminated separately from axons and immune cells in the proximal stump of cut nerves, from cells in the regeneration pathway, or both. Two weeks later, axons from wild type mice regenerating into grafts devoid of p75 NTR had elongated more than twice as far as axons in grafts from wild type mice. No enhancement of regeneration of axons in p75 NTR knockout mice was observed, whether nerves were repaired with grafts from wild type mice or from p75 NTR knockout mice. To evaluate whether inhibition of p75 NTR could be used to improve regeneration, nerves in wild type mice repaired without grafts were exposed to a specific inhibitor of the p75 NTR receptor, LM11A-31, at the time of nerve repair. This local blockade of p75 NTR resulted in successful regeneration of axons of nearly three times as many motoneurons and reinnervation of twice as many muscle fibers by regenerating motor axons as untreated controls. Expression of p75 NTR surrounding regenerating axons contributes to poor regeneration during the first 2 weeks after peripheral nerve injury. Inhibition of p75 NTR might be a therapeutic target for treatments of peripheral nerve injuries., (© 2020 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.)

Introduction: Tuina is currently one of the popular complementary and alternative methods of rehabilitation therapy. Tuina can improve patients' pain and mobility function. However, the underlying physiological mechanism remains largely unknown, which might limit its further popularization in clinical practice. The aim of this study is to explore the short‐term and long‐term changes in brain functional activity following Tuina intervention for peripheral nerve injury repair. Methods: A total of 16 rats were equally divided into the intervention group and the control group. Rats in the intervention group received Tuina therapy applying on the gastrocnemius muscle of the right side for 4 months following sciatic nerve transection and immediate repair, while the control group received nerve transection and repair only. The block‐design functional magnetic resonance imaging scan was applied in both groups at 1 and 4 months after the surgery. During the scan, both the injured and intact hindpaw was electrically stimulated according to a "boxcar" paradigm. Results: When stimulating the intact hindpaw, the intervention group exhibited significantly lower activation in the somatosensory area, limbic/paralimbic areas, pain‐regulation areas, and basal ganglia compared to the control group, with only the prefrontal area showing higher activation. After 4 months of sciatic nerve injury, the control group exhibited decreased motor cortex activity compared to the activity observed at 1 month, and the intervention group demonstrated stronger bilateral motor cortex activity compared to the control group. Conclusion: Tuina therapy on the gastrocnemius muscle of rats with sciatic nerve injury can effectively alleviate pain and maintain the motor function of the affected limb. In addition, Tuina therapy reduced the activation level of pain‐related brain regions and inhibited the decreased activity of the motor cortex caused by nerve injury, reflecting the impact of peripheral stimulation on brain plasticity. [ABSTRACT FROM AUTHOR]

The article discusses the physiological and behavioral considerations for managing horses with tail disorders. It highlights the importance of the horse's tail in communication, temperature regulation, and protection of delicate structures. Various tail disorders such as fractures, tail paralysis, and sacrococcygeal luxation are mentioned, with treatment options ranging from conservative to surgical interventions. The article also addresses the historical practice of tail docking and emphasizes the importance of preserving the horse's tail for its well-being and communication purposes. [Extracted from the article]

Peripheral nerve injuries (PNIs) include complete and partial transection, crushing, and chronic compression injuries. Hollow absorbable conduits are used to treat complete transection with short defects, while wrapping the injured part with an absorbent material promotes nerve recovery by inhibiting inflammatory cell infiltration and scar tissue formation in crush injuries. For treatment of partially transected nerve injuries (PTNIs), such as injection‐related iatrogenic PNI, whether wrapping the entire nerve, including the injury site, or bridging the transected fascicle with an artificial nerve conduit (ANC) is beneficial remains to be verified. The purpose of this study was to investigate whether wrapping the injured nerve and placing collagen fibers as scaffolds at the nerve defect site contribute to neural recovery in PTNI. A unilateral 5‐mm partial nerve defect was created at the mid‐thigh level in a rat sciatic nerve injury model. Fifty‐four Sprague–Dawley (SD) rats (150–250 g) were divided into three groups (n = 9 each): group 1, collagen fibers were placed in the nerve defect and the sciatic nerve was wrapped with collagen conduit; group 2, the sciatic nerve was wrapped by collagen conduit without collagen fibers; and group 3, nerve defect was reconstructed with collagen‐filled conduit. Nerve regeneration was evaluated by analyses of gait, electrophysiology, wet muscle weight, and axon numbers with immunohistochemistry at 12 and 24 weeks. Dorsiflexion angles among all groups improved significantly from 12 to 24 weeks postoperatively. At 24 weeks postoperatively, compound muscle action potential amplitudes (CMAPs) of tibialis anterior were 5.26 ± 4.64, 1.31 ± 1.17, and 0.14 ± 0.24 mV (p <.05), CMAPs of gastrocnemius were 21.3 ± 5.98, 15.4 ± 5.46, and 13.11 ± 3.91 mV in groups 1, 2, and 3, respectively; and the value of group 1 was significantly higher than that of group 3 (p <.05). Axon numbers were 2194 ± 629; 1106 ± 645; and 805 ± 907 in groups 1, 2, and 3, respectively (p <.05). For PTNI reconstruction, artificial nerve wrap (ANW) was superior to ANC. Providing collagen scaffold at the nerve defect site enhanced nerve recovery during reconstruction with ANW. [ABSTRACT FROM AUTHOR]

Peripheral nerves (PNs) are frequently injured as a result of trauma or disease. Development of therapies to regenerate PNs requires the use of animal models, typically beginning in rodents and progressing to larger species. There are several large animal models of PN regeneration that each has their benefits and drawbacks. Sheep have been used in PN studies due to their similarities in body weight to humans and the ease and lesser expense in their care and housing relative to other species. We have investigated the use of sheep for studies of PN regeneration and have developed and tested an injury model in the peroneal branch of the sciatic nerve. Three experimental groups were tested on mature sheep: a bisection; a 5-cm reverse autograft; and sham surgery. Protocols were developed for the post-operative care for animals with this injury, and regeneration was tracked for extended time points via compound muscle action potentials (CMAPs) and endpoint assessments of nerve morphometry, muscle mass and muscle fibrosis. Results indicate the practical viability of this PN injury model and show distinctions in the degree and rate of regeneration between bisection and reverse autograft that persisted 14 months. This long-term study shows bisections lead to significantly improved CMAPS and muscle mass and lesser muscle fibrosis as compared to reverse autograft. The persistence of these discernable changes between two relatively similar experimental groups out to extended time points is an indication of the sensitivity of this nerve section and its potential applicability for comparative studies., (© 2020 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.)

Accurate localization and characterization of peripheral nerve injuries adjacent to metallic hardware is difficult with magnetic resonance imaging (MRI) due to susceptibility artifact. This study sought to present the use of high‐resolution ultrasound (US) in accurate characterization of radial nerve injury adjacent to metallic hardware, using findings at the time of operative exploration as confirmation of the US assessment. A retrospective chart review of cases with clinically identified radial nerve injuries evaluated by the high‐resolution US was performed from January 2015 through December 2019. Preoperative clinical data, US reports, MRI reports, electrodiagnostic (EDx) reports, and operative reports were reviewed for each case. Preoperative US correctly characterized the affected nerve component, type, and location of injury in all 13 cases (100%), when correlated with intraoperative findings. Nerve injury was directly adjacent to metallic hardware in 12 cases (92%). Out of the seven cases evaluated by both US and MRI, US correctly accurately diagnosed radial nerve injuries in all cases, whereas MRI accurately diagnosed in four cases (57%). In 3/7 cases (43%) MRI was nondiagnostic due to susceptibility artifact. MRI evaluation of the nerve was limited to some degree by metallic artifact in 6/7 cases (85%). [ABSTRACT FROM AUTHOR]

Background: Cavernosal fibrosis, which is induced by cavernosal nerve (CN) injury and progresses with time, is the main cause of cavernosal veno-occlusive dysfunction (CVOD) after radical prostatectomy., Objectives: To determine whether daily oral administration of suberoylanilide hydroxamic acid (SAHA; vorinostat) for 5-weeks from the immediate post-injury period after CN injury would rectify CVOD by suppressing cavernosal fibrosis and normalizing HDAC pathway in a rat model of CN crush injury (CNCI) and to compare the results with those obtained using chronic administration of PDE5-inhibitors (a positive control)., Methods: Fifty-six 12-week-old rats were randomized into the four groups: sham surgery (S), CNCI (I), and CNCI treated with daily administration of 25.0 mg/kg SAHA (V) or 20.0 mg/kg udenafil (P). Group-V and Group-P received the respective treatment for 5-weeks from the following day after CNCI. At 5 weeks after surgery, dynamic infusion cavernosometry (DIC), histological staining, and Western blot analysis were performed., Results: Group-I had a significantly decreased papaverine response, higher maintenance rate or drop rate, lower smooth muscle (SM)/collagen ratio, decreased SM content, and increased protein expression of HDAC2, HDAC3, TGF-β1, and collagen-1, compared with Group-S. The three DIC parameters in Group-V and Group-P significantly improved compared to those in Group-I. Except for the maintenance rate, the improvement in papaverine response and drop rate in Group-V was not significantly different from that in Group-P. Group-V and Group-P showed the rectification of SM/collagen ratio and protein expression of TGF-β1 or collagen-1. SM content was improved in Group-P, but not in Group-V. Group-V showed the normalization of protein expression of both HDAC2 and HDAC3, whereas protein expression of only HDAC2 was partially restored in Group-P., Discussion: Treatment strategies targeting the HDAC pathway might be helpful to alleviate CVOD induced by CN injury., Conclusions: According to our data, chronic administration of SAHA improves post-injury CVOD by suppressing cavernosal fibrosis via rectifying the HDAC/TGF-β1 pathway in nerve-injured rats, comparable to that with PDE5 inhibitors., (© 2020 American Society of Andrology and European Academy of Andrology.)

Peripheral nerve injury (PNI) is a common and incurable disease in the clinic, but the effects of available treatments are still not satisfactory. Therefore, it is necessary to explore new treatment methods. To explore the effect and mechanism of melatonin in peripheral nerve regeneration, we administered melatonin to mice with PNI by intraperitoneal injection. We applied microarray analysis to detect differentially expressed genes of mice with sciatic nerve injury after melatonin application. Then, we conducted gene ontology and protein-protein interactions to screen out the key genes related to peripheral nerve regeneration. Cell biology and molecular biology experiments were performed in Schwann cells in vitro to verify the key genes identified by microarray analysis. Our results showed that a total of 598 differentially expressed genes were detected after melatonin subcutaneously injecting into mice with sciatic nerve injury. Bioinformatics analysis showed that Shh may be the key gene for the promotion of peripheral nerve regeneration by melatonin. In vitro, the proliferation and migration abilities of schwann cells in the melatonin group were significantly higher than those of Schwann cells in the control group; while after treating with both melatonin and luzindole (a Shh signalling pathway inhibitor), the proliferation and migration abilities of Schwann cells decreased compared with the melatonin group. Our study suggests that melatonin might improve the proliferation and migration of Schwann cells via the Shh signalling pathway after PNI, thus promoting peripheral nerve regeneration. Our study provides a new approach and target for the clinical treatment of PNI., (© 2020 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.)

Background: Radical prostatectomy induces some degree of cavernous nerve injury (CNI) and causes denervation-induced pathologic changes in cavernous vasculature, regardless of the advances in surgical techniques and robotic procedures. The precursor for nerve growth factor (proNGF) is known to be involved in neuronal cell apoptosis and microvascular dysfunction through its receptor p75 NTR ., Objectives: To determine the expression of proNGF/p75 NTR and the efficacy of proNGF neutralizing antibody (anti-proNGF-Ab) in a mouse model of ED induced by CNI., Materials and Methods: Age-matched 12-week-old C57BL/6 mice were distributed into three groups: sham group and bilateral CNI group treated with intracavernous injections of PBS (20 μL) or of anti-proNGF-Ab (20 µg in 20 μL of PBS) on days -3 and 0. Two weeks after treatment, erectile function was measured by electrical stimulation of cavernous nerve. Penis tissues from a separate group of animals were harvested for further analysis. We also determined the efficacy of anti-proNGF-Ab on neural preservation in major pelvic ganglion (MPG) ex vivo., Results: We observed increased penile expression of proNGF and p75 NTR after CNI. Intracavernous administration of anti-proNGF-Ab increased nNOS and neurofilament expression probably by enhancing the production of neurotrophic factors, such as neurotrophin-3, NGF, and brain-derived neurotrophic factor. Anti-proNGF-Ab preserved the integrity of cavernous sinusoids, such as pericytes, endothelial cells, and endothelial cell-to-cell junctions, possibly by controlling angiogenic factors (angiopoietin-1, angiopoietin-2, and vascular endothelial growth factor) and induced endogenous eNOS phosphorylation in CNI mice. And finally, treatment with anti-proNGF-Ab rescued erectile function in CNI mice. Anti-proNGF-Ab also enhanced neurite sprouting from MPG exposed to lipopolysaccharide., Discussion and Conclusion: The preservation of damaged cavernous neurovasculature through inhibition of the proNGF/p75 NTR pathway may be a novel strategy to treat radical prostatectomy-induced erectile dysfunction., (© 2020 American Society of Andrology and European Academy of Andrology.)

Objective: Nerve pain frequently develops following amputations and peripheral nerve injuries. Two innovative surgical techniques, targeted muscle reinnervation (TMR) and regenerative peripheral nerve interfaces (RPNI), are rapidly gaining popularity as alternatives to traditional nerve management, but their effectiveness is unclear. Literature Survey: A review of literature pertaining to TMR and RPNI pain results was conducted. PubMed and MEDLINE electronic databases were queried. Methodology: Studies were included if pain outcomes were assessed after TMR or RPNI in the upper or lower extremity, both for prophylaxis performed at the time of amputation and for treatment of postamputation pain. Data were extracted for evaluation. Synthesis: Seventeen studies were included, with 14 evaluating TMR (366 patients) and three evaluating RPNI (75 patients). Of these, one study was a randomized controlled trial. Nine studies had a mean follow‐up time of at least 1 year (range 4–27.6 months). For pain treatment, TMR and RPNI improved neuroma pain in 75%–100% of patients and phantom limb pain in 45%–80% of patients, averaging a 2.4–6.2‐point reduction in pain scores on the numeric rating scale postoperatively. When TMR or RPNI was performed prophylactically, many patients reported no neuroma pain (48%–100%) or phantom limb pain (45%–87%) at time of follow‐up. Six TMR studies reported Patient‐Reported Outcomes Measurement Information System (PROMIS) scores assessing pain intensity, behavior, and interference, which consistently showed a benefit for all measures. Complication rates ranged from 13% to 31%, most frequently delayed wound healing. Conclusions: Both TMR and RPNI may be beneficial for preventing and treating pain originating from peripheral nerve dysfunction compared to traditional techniques. Randomized trials with longer term follow‐up are needed to directly compare the effectiveness of TMR and RPNI with traditional nerve management techniques. [ABSTRACT FROM AUTHOR]

Peripheral nerve injury and the nerves' subsequent repair and regeneration continues to be marked clinically by poor functional recovery. The analysis of nerve morphology is an aspect which may provide an impact on successful clinical outcomes through better prediction of donor and recipient matching. In this study, we evaluated the morphological aspects of the human obturator nerve for a better understanding of its potential in nerve transplantation. Morphological characteristics of donor obturator nerves were analysed, including nerve diameter and length, fascicle count and the ratio of neural to non‐neural tissue present within the cross‐sectional area of the nerve's epineurium, with respect to laterality and sex. Statistical significance (p < 0.10) was determined for male obturator nerves having an average diameter of 2.67 mm compared to female obturator nerves at 1.91 mm, as well as left obturator nerves having an average of 11.21 fascicles compared to the right having an average of 10.17 fascicles. Strong positive correlations were determined between cross‐sectional nerve area and limb size index, as well as between percentage of non‐neural tissue and area of non‐neural tissue, among males. Separately, strong correlation between percentage of non‐neural tissue and area of non‐neural tissue among right obturator nerves in males and females was determined. These findings indicate that there are associations and predictions that can be made about nerve morphology and that these when combined with other patient characteristics may enhance patient functional recovery following a peripheral nerve's repair. [ABSTRACT FROM AUTHOR]

The objectives of this study were (1) epidemiological analysis of traumatic peripheral nerve injuries; (2) assessment of neuropathic pain and quality of life in patients affected by traumatic neuropathies. All consecutive patients with a diagnosis of traumatic neuropathies from four Italian centres were enrolled. Electromyography confirmed clinical level and site diagnosis of peripheral nerve injury. All patients were evaluated by disability scales, pain screening tools, and quality of life tests. 158 consecutive patients for a total of 211 traumatic neuropathies were analysed. The brachial plexus was a frequent site of traumatic injury (36%) and the radial, ulnar, and peroneal were the most commonly involved nerves with 15% of iatrogenic injuries. Seventy-two percent of the traumatic neuropathies were painful. Pain was present in 66% and neuropathic pain in 50% of all patients. Patients had worse quality of life scores than did the healthy Italian population. Moreover, there was a strong correlation between the quality of life and the severity of the pain, particularly neuropathic pain (Short Form-36 [SF-36] p < 0.005; Beck Depression Inventory [BDI] p < 0.0001). Traumatic neuropathies were more frequent in young males after road accidents, mainly in the upper limbs. Severe neuropathic pain and not only disability contributed to worsening the quality of life in patients with traumatic neuropathies. [ABSTRACT FROM AUTHOR]

A correction to the article "Serum neurofilament light chain measurements following nerve trauma" in the J Peripher Nerv Syst. (2023;28(3):500–507) issue is presented which discusses an error in the serum neurofilament light chain data analysis.

Peripheral nerve injury (PNI) remains a challenging area in regenerative medicine. Nerve guide conduit (NGC) transplantation is a common treatment for PNI, but the prognosis of NGC treatment is unsatisfactory due to 1) neuromechanical unmatching and 2) the intra‐conduit inflammatory microenvironment (IME) resulting from Schwann cell pyroptosis and inflammatory‐polarized macrophages. A neuromechanically matched NGC composed of regenerated silk fibroin (RSF) loaded with poly(3,4‐ethylenedioxythiophene): poly(styrene sulfonate) (P:P) and dimethyl fumarate (DMF) are designed, which exhibits a matched elastic modulus (25.1 ± 3.5 MPa) for the peripheral nerve and the highest 80% elongation at break, better than most protein‐based conduits. Moreover, the NGC can gradually regulate the intra‐conduit IME by releasing DMF and monitoring sciatic nerve movements via piezoresistive sensing. The combination of NGC and electrical stimulation modulates the IME to support PNI regeneration by synergistically inhibiting Schwann cell pyroptosis and reducing inflammatory factor release, shifting macrophage polarization from the inflammatory M1 phenotype to the tissue regenerative M2 phenotype and resulting in functional recovery of neurons. In a rat sciatic nerve crush model, NGC promoted remyelination and functional and structural regeneration. Generally, the DMF/RSF/P:P conduit provides a new potential therapeutic approach to promote nerve repair in future clinical treatments. [ABSTRACT FROM AUTHOR]

Background: Charcot–Marie–Tooth (CMT) disease is the most frequent hereditary motor sensory neurological disease. GJB1 gene is the second most frequent cause of CMT, accounting for approximately 10% of CMT cases worldwide. We identified a large Han family with X‐linked CMT disease. Methods: In this study, the probands and his mother underwent electrophysiological examinations and other family members were assessed retrospectively. Whole‐exome sequencing, Sanger sequencing, and SNP array linkage analysis were performed to find and confirm the variant. The functional effect of the identified variant was further investigated in HEK293 cells and MCF‐7 cells by minigene splicing assay. Results: The affected individuals had some clinical symptoms including symmetric atrophy and progressive weakness of the distal muscles in their twenties. Electrophysiological examinations result in peripheral nerve injury of the upper and lower limbs. Whole‐exome sequencing identified a novel hemizygous deletion mutation (NM_000166: c.‐16‐8_‐14del) in the GJB1 gene. SNP array linkage analysis and co‐segregation analysis confirmed this mutation. Minigene splicing assay verified that this mutation leads to the activation of cryptic splicing sites in exon 2 which results in the deletion of exon 2. Conclusion: Our study provides theoretical guidance for prenatal diagnosis and subsequent fertility of this family. This result expands the spectrum of mutations in GJB1 known to be associated with CMTX and contributes to the diagnosis of CMT and clinical genetic counseling. [ABSTRACT FROM AUTHOR]

Background: Men and women with chronic pain report increased alcohol use and are more likely to be diagnosed with alcohol use disorder. The relationship between alcohol use and pain is bidirectional. Alcohol is used as an analgesic, but chronic alcohol intake increases pain. Sex differences in the relationship between chronic pain and alcohol are reported in the clinical and preclinical literature, but due to this bidirectional relationship, it is challenging to investigate the mechanisms that contribute to these differences. Thus, animal models of chronic pain are needed to characterize the efficacy of ethanol as an analgesic in males and females. The current experiments tested the hypothesis that ethanol differentially reduces pain behaviors in male and female mice in chronic neuropathic pain. Methods: The spared nerve injury (SNI) model was used to investigate the analgesic effects of multiple doses of ethanol (0.5, 1, 2, g/kg i.p.) in male and female mice using von Frey and dynamic weight‐bearing (DWB) assays. Results: In both male and female mice, SNI led to robust allodynia and shifts in dynamic weight bearing. In male SNI mice, all three doses of ethanol fully reversed mechanical allodynia and shifts in DWB. In SNI females, only the highest dose (2.0 g/kg) was fully antiallodynic in the von Frey assay, while shifts in weight bearing were reversed at the 1.0 and 2.0 g/kg doses. The differences between male and females were not due to lower blood ethanol concentrations in female mice. Conclusion: These data indicate that while ethanol has antiallodynic and antinociceptive effects in male and female mice, the doses and time course of these effects are distinct. Studies investigating the relationship between pain and ethanol exposure in mice should consider sex as a key variable. These data also inform reported sex differences in rodent models of chronic pain and in chronic pain patients. [ABSTRACT FROM AUTHOR]

Peripheral nerve injury (PNI) remains an intractable challenge in regenerative medicine. Recently, physical cue‐based strategies (e.g., electrical neurostimulation, acoustic radiation, electromagnetic bioregulation, as well as directional fiber guiding, etc.) have drawn increasing attention not only as a stimulator for cell functions modulation and fate determination, but also as a morphology‐index for modulating cell phenotype, proliferation, and differentiation, especially for nerve cells. More importantly, the advanced percutaneous power transmission technology, self‐power nanotechnology that leverages piezoelectrical/triboelectricity materials, and focused ultrasound and pulsed electromagnetic field technology exhibit the appealing practice potential for achieving low‐invasive, wireless, and battery‐free neuromodulation. In this review, recent advances of physical cue‐based strategies including electrical, acoustic, magnetic, and morphology for PNI are systematically overviewed, and the open challenges for realizing scalable clinical/commercial transformation and future perspectives of these strategies for PNI are concluded. [ABSTRACT FROM AUTHOR]

Nerve transfer or grafting surgery to restore elbow flexion in peripheral nerve injuries has been an effective technique, but alters neuromuscular control compared with healthy individuals. This study compared neuromuscular control in the elbow flexors of 11 unimpaired control subjects and 11 adult patients with traumatic brachial plexus injury who underwent a nerve transfer or grafting procedure to the biceps motor branch to restore elbow flexion. The subjects performed a series of trials to generate a specific percentage of their maximum elbow torque. Each trial had an increasing and decreasing stairstep torque pattern that the subjects were asked to match. The amount of time that the subject's elbow torque was maintained within 5% of the target torque was calculated. The hypothesis was that there was a significant difference in the neuromuscular control between the two groups during elbow isometric torque generation. A secondary hypothesis was that a relationship existed between the neuromuscular control and the torque level for each group. The results demonstrated that neuromuscular control was different between the groups and there were significant differences in how torque levels are generated. The control group more easily modulated their myoelectric activation and achieved greater neuromuscular control variability with varying torque demand. The nerve transfer or grafting group could not modulate their myoelectric activation with changing torque demands. Further studies focusing on the improvement of neuromuscular control are needed to optimize functional outcomes in nerve injury patients. [ABSTRACT FROM AUTHOR]

There is no effective treatment for peripheral nerve injury-induced chronic neuropathic pain (NP), which profoundly impacts the quality of life of those affected. Transmembraneprotein100 (TMEM100) is considered to be a pain regulatory protein and is expressed in the dorsal root ganglion (DRG) of rats. However, the mechanism of pain regulation and the expression of TMEM100 following various peripheral nerve injuries are unclear. In this study, we constructed two pain models of peripheral nerve injury: tibial nerve injury (TNI) and chronic constriction injury (CCI). This study found that the Paw Withdrawal Mechanical Threshold (PWMT) and Paw Withdraw Thermal Latency (PWTL) of the rats in the two pain models decreased significantly, and the expression of TMEM100 in the DRG of two groups also decreased significantly. Furthermore, the decrease in the CCI group was more obvious than in the TNI group. There was no significant statistical significance (P > 0.05). We constructed an adeno-associated virus 6 (AAV6) vector expressing recombinant fluorescent TMEM100 protein and injected it into the sciatic nerve (SN) of two pain models: CCI and TNI. PWMT and PWTL were significantly increased in the two groups, along with the expression of TMEM100 in the spinal cord and DRG. It also significantly inhibited the activation of microglia, astrocytes, and several inflammatory mediators (TNF- α, IL-1 β, and IL-6). In summary, the results of this study suggested that TMEM100 might be a promising molecular strategy for the treatment of NP, and its anti-inflammatory effects might play an important role in pain relief. [ABSTRACT FROM AUTHOR]

Peripheral nerve injury results in limited nerve regeneration and severe functional impairment. Mesenchymal stem cells (MSCs) are a remarkable tool for peripheral nerve regeneration. The involvement of human umbilical cord MSC-derived extracellular vesicles (hUCMSC-EVs) in peripheral nerve regeneration, however, remains unknown. In this study, we evaluated functional recovery and nerve regeneration in rats that received hUCMSC-EV treatment after nerve transection. We observed that hUCMSC-EV treatment promoted the recovery of motor function and the regeneration of axons; increased the sciatic functional index; resulted in the generation of numerous axons and of several Schwann cells that surrounded individual axons; and attenuated the atrophy of the gastrocnemius muscle. hUCMSC-EVs aggregated to rat nerve defects, down-regulated interleukin (IL)-6 and IL-1β, up-regulated IL-10 and modulated inflammation in the injured nerve. These effects likely contributed to the promotion of nerve regeneration. Our findings indicate that hUCMSC-EVs can improve functional recovery and nerve regeneration by providing a favourable microenvironment for nerve regeneration. Thus, hUCMSC-EVs have considerable potential for application in the treatment of peripheral nerve injury., (© 2019 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.)

Peripheral nerve injuries are largely preventable injuries that can result from incorrect patient positioning during surgery. Patients who are diabetic, are extremely thin or obese, use tobacco, or undergo surgery lasting more than four hours are at increased risk for developing these injuries. When peripheral nerve injuries occur, patients may experience numbness, burning, or tingling and may have difficulty getting out of bed, walking, gripping objects, or raising their arms. These symptoms can interrupt activities of daily living and impede recovery. Signs and symptoms of peripheral nerve injury may appear within 24 to 48 hours of surgery or may take as long as a week to appear. Careful attention to body alignment and proper padding of bony prominences when positioning patients for surgery is necessary to prevent peripheral nerve injury. The use of a preoperative assessment tool to identify at-risk patients, collaboration between physical therapy and OR staff members regarding patient positioning, and neurophysiological monitoring can help prevent peripheral nerve injuries. [ABSTRACT FROM AUTHOR]

Background: Peripheral nerve defects (PND) often cause lifelong physical disability, and the available treatment options are often not satisfactory. PND are usually bridged with an autologous nerve transplant or a nerve guidance conduit (NGC), when coaptation as preferred technique is not possible. The aim of this experimental study was to determine the effectiveness of a novel NGC for regeneration in the treatment of PND. Materials and methods: A conduit made of gelatin with an innovative interior structure was tested for the repair of a 6-mm gap versus direct microsurgical suture repair without gap. Results: We found that bridging the defect with this conduit was as effective as direct microsurgical coaptation without a defect. Conclusions: This nerve conduit, effective in bridging neural defects, appears as an alternative to autologous nerve grafts, avoiding the problems related to nerve graft harvesting, host–donor differences in diameter, mismatches in number and pattern of fascicles, cross-sectional shape and area, and morbidity of the donor area. [ABSTRACT FROM AUTHOR]

Peripheral nerve injuries are one of those complex medical conditions for which a highly effective first‐line treatment is currently missing. The use of natural compound as medicines to treat various disorders has a long history. Our previous research explored that crude Cannabis sativa L. accelerated the recovery of sensorimotor functions following nerve injury. The purpose of the current study was to investigate the effects of n‐Hexane and ethyl acetate extracts of C. sativa L. leaves on the muscle function restoration in a mouse model after sciatic nerve injury. For this purpose, albino mice (n = 18) were equally divided into control and two treatment groups. The control group was fed on a plain diet while treatment groups were given a diet having n‐Hexane (treatment 1) and ethyl acetate (treatment 2) extracts of C. sativa L. (10 mg/kg body weight), respectively. The hot plate test (M = 15.61, SD = 2.61, p =.001), grip strength (M = 68.32, SD = 3.22, p <.001), and sciatic functional index (SFI) (M = 11.59, SD = 6.54, p =.012) assessment indicated significant amelioration in treatment 1 as compared to treatment 2 group. Furthermore, muscle fiber cross‐sectional area revealed a noticeable improvement (M = 182,319, SD = 35.80, p =.013) in treatment 1 while muscle mass ratio of Gastrocnemius (M = 0.64, SD = 0.08, p =.427) and Tibialis anterior (M = 0.57, SD = 0.04, p =.209) indicated nonsignificant change. A prominent increase in total antioxidant capacity (TAC) (M = 3.76, SD = 0.38, p <.001) and momentous decrease in total oxidant status (TOS) (M = 11.28, SD = 5.71, p <.001) along with blood glucose level indicated significant difference (M = 105.5, SD = 9.12, p < 0.001) in treatment 1 group. These results suggest that treatment 1 has the ability to speed up functional recovery after a peripheral nerve lesion. Further research is necessary, nevertheless, to better understand the extract's actual curative properties and the mechanisms that improve functional restoration. [ABSTRACT FROM AUTHOR]

Globally, peripheral nerve injury (PNI) is a common clinical issue. Successfully repairing severe PNIs has posed a major challenge for clinicians. GW3965 is a highly selective LXR agonist, and previous studies have demonstrated its positive protective effects in both central and peripheral nerve diseases. In this work, we examined the potential reparative effects of GW3965‐loaded polylactic acid co‐glycolic acid microspheres in conjunction with a chitosan nerve conduit for peripheral nerve damage. The experiment revealed that GW3965 promoted Schwann cell proliferation and neurotrophic factor release in vitro. In vivo experiments conducted on rats showed that GW3965 facilitated the restoration of motor function, promoted axon and myelin regeneration in the sciatic nerve, and enhanced the microenvironment of nerve regeneration. These results offer a novel therapeutic approach for the healing of nerve damage. Overall, this work provides valuable insights and presents a promising therapeutic strategy for addressing PNI. [ABSTRACT FROM AUTHOR]

Exosomes are the smallest subset of extracellular signaling vesicles secreted by most cells with the ability to communicate with other tissues and cell types over long distances. Their use in regenerative medicine has gained tremendous momentum recently due to their ability to be utilized as therapeutic options for a wide array of diseases/conditions. Over 5000 publications are currently being published yearly on this topic, and this number is only expected to dramatically increase as novel therapeutic strategies continue to be developed. Today exosomes have been applied in numerous contexts including neurodegenerative disorders (Alzheimer's disease, central nervous system, depression, multiple sclerosis, Parkinson's disease, post‐traumatic stress disorders, traumatic brain injury, peripheral nerve injury), damaged organs (heart, kidney, liver, stroke, myocardial infarctions, myocardial infarctions, ovaries), degenerative processes (atherosclerosis, diabetes, hematology disorders, musculoskeletal degeneration, osteoradionecrosis, respiratory disease), infectious diseases (COVID‐19, hepatitis), regenerative procedures (antiaging, bone regeneration, cartilage/joint regeneration, osteoarthritis, cutaneous wounds, dental regeneration, dermatology/skin regeneration, erectile dysfunction, hair regrowth, intervertebral disc repair, spinal cord injury, vascular regeneration), and cancer therapy (breast, colorectal, gastric cancer and osteosarcomas), immune function (allergy, autoimmune disorders, immune regulation, inflammatory diseases, lupus, rheumatoid arthritis). This scoping review is a first of its kind aimed at summarizing the extensive regenerative potential of exosomes over a broad range of diseases and disorders. [ABSTRACT FROM AUTHOR]

Neurological function recovery after peripheral nerve injury (PNI) is exceptionally challenging, chiefly because neurons cannot efficiently proliferate, differentiate, and form regenerated axons to pass through the defect region expeditiously and transmit neurological signals. In this study, a four‐dimensional (4D) oriented dynamic scaffold is constructed based on shape memory polymer (SMP), which can regulate spatiotemporally controllable neuronal early adequate proliferation, subsequently effective differentiation and axon formation by synergizing the on‐demand microtopography and deformation force‐based mechanical stimuli (DFMS). This dynamic scaffold can accelerate the restoration of large segmental nerve defects, elevate the neural signaling efficiency by 60% compared with static scaffold, and finally form the functionalized robust regenerating nerve fascicles with comparable therapeutic effects on autologous nerve transplantation. Furthermore, the crucial role of Piezo1/Camk2b modulated neuronal differentiation and axon extension is also revealed through deep transcriptomic analysis. In summary, the 4D oriented dynamic scaffold can precisely and remotely regulate neuronal behavior and fate in a non‐invasive way, which has excellent potential for clinical application in peripheral nerve restoration. [ABSTRACT FROM AUTHOR]

Autograft replaced by a nerve guidance conduit (NGC) is challenging in peripheral nerve injury because current NGC is still limited by precise conductivity and excellent biocompatibility in vivo, which influences the peripheral nerve repair even for a long lesion gap repair. Several particular elements have the potential function for nerve conductivity acceleration based on the traditional three factors of neural tissue engineering. The review aims to address three questions: 1) What is the superior factor for nerve conduction in the application? 2) How can a more conductive regenerative scaffold be constructed in vivo? 3) What is the next step in nerve regeneration for NGC? The bibliometrics analysis of NGC‐related references is adopted to acquire that the conductive material, manufacturing technology of neural scaffold, and electrical stimulation (ES) play essential roles in the acceleration of nerve conduction. This review visually analyses the research status and summarizes the main types of conductive materials, the manufacturing technologies of neural scaffolds, and the characteristics of ES. The viewpoints and outlook of developing NGC are also discussed in this review. The proposed three elements are expected to improve the nerve conduction of NGC in vivo and even address the dilemma of long‐distance peripheral nerve injury. [ABSTRACT FROM AUTHOR]

Postradical prostatectomy erectile dysfunction (pRP-ED) is a major health issue. There has been a shortage of an effective treatment method until now. In this study, a total of 48 adult male Sprague-Dawley (SD) rats were randomly equally divided into four groups, including group 1-sham surgery with cavernous nerve exposure plus vehicle, group 2-bilateral cavernous nerve injury (BCNI) plus vehicle, group 3-BCNI plus adipose-derived mesenchymal stem cells (ADSCs)-derived exosomes (ADSC-Exo), and group 4-BCNI plus bone marrow-derived mesenchymal stem cell (BMSCs)-derived exosomes (BMSC-Exo). Twenty-one days following surgery, erectile function was measured before tissue harvest. Histologic and Western blot analyses were then performed. Exosomes were capable of internalization into human umbilical vein endothelial cells (HUVEC) in vitro and could be detected in the corpus cavernosum in vivo. The nNOS expression in the penile dorsal nerves (DN) and major pelvic ganglion (MPG), protein level of neurofilament in the DN, endothelial markers vWF, alpha smooth muscle actin (α-SMA), the ratio of smooth muscle to collagen content were obviously lower in BCNI group compared with the sham group, while ADSC-Exo and BMSC-Exo groups resulted in significant restoration of the above histopathological changes. Moreover, BCNI treated with ADSC-Exo or BMSC-Exo had significantly higher mean intracavernous pressure/mean arterial pressure ratio compared with BCNI group. The results demonstrated that both ADSC-Exo and BMSC-Exo treatment could significantly alleviate pathological changes and improve the erectile function in BCNI-related rats. Exosomes derived from ADSCs and BMSCs may be a potential agent for pRP-ED treatment., (© 2018 American Society of Andrology and European Academy of Andrology.)

Background: The reported incidence of phrenic nerve injury (PNI) varies owing to different definitions, balloon generations, balloon size, freezing regimen, and protective maneuvers. We evaluated the incidence, predictors, and outcome of PNI during cryoballoon pulmonary vein isolation in a large population., Methods and Results: Five hundred fifty atrial fibrillation patients underwent pulmonary vein isolation using one 28-mm second-generation cryoballoon and single 3-minute freeze strategy under diaphragmatic compound motor action potential (CMAP) monitoring. A total of 34 (6.2%) patients experienced PNI during the right superior and inferior pulmonary vein ablation in 30 and 4 patients, respectively. Applications were interrupted using double-stop techniques after 136 [104-158] second applications, and a pulmonary vein isolation was already achieved in all but one case. The baseline CMAP amplitude and timing of deflation (CMAP def ) were 0.75±0.30 and 0.17±0.17 mV, respectively. Persistent atrial fibrillation, larger right superior pulmonary vein ostia, and deeper balloon positions were associated with higher incidences of PNI. The CMAP def predicted a PNI recovery delay, and the best cutoff value for predicting PNI recovery by the next day was 0.20 mV (sensitivity 57.1%, specificity 100%). Among 6 patients undergoing second procedures 8.5 (6.7-15.0) months later, the right superior pulmonary vein was durable in 3 with >120 second applications. Despite active balloon deflation, no significant pulmonary vein stenosis was observed in 15 right superior pulmonary veins evaluated 6 (5-9) months later. No patients had symptoms, and the PNI recovered 1 day and 1 month postprocedure in 21 and 4 patients, respectively., Conclusions: PNI resulting from cryoballoon ablation was reversible. The double-stop technique is safe, and immediate active deflation following a CMAP decrease appears to be essential for faster PNI recovery., (© 2018 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.)

In this article, we will discuss the pathophysiology of peripheral nerve injury in anaesthetic practice, including factors which increase the susceptibility of nerves to damage. We will describe a practical and evidence-based approach to the management of suspected peripheral nerve injury and will go on to discuss major nerve injury patterns relating to intra-operative positioning and to peripheral nerve blockade. We will review the evidence surrounding particular strategies to reduce the incidence of peripheral nerve injury during nerve blockade, including nerve localisation methods, timing of blocks, needle techniques and design, injection pressure-monitoring and local anaesthetic and adjunct choice., (© 2018 The Association of Anaesthetists of Great Britain and Ireland.)

Background: This was a multicenter, double-blind, randomized clinical trial to investigate the efficacy of electrical stimulation of denervated muscle (ESDM) on recovery of patients with peripheral nerve injuries.Methods: We enrolled 38 patients with traumatic peripheral nerve injuries with axonal damage and clinical impairment of two muscles, who were randomly treated with real or sham electrical stimulation (ES). Clinical and neurophysiological examinations were performed before treatment, at the end of treatment, and 3 mo posttreatment, by the same physician who was blinded to the ES allocation.Results: All patients improved but there was no significant beneficial effect of ESDM compared with sham treatment.Conclusions: This study failed to demonstrate the efficacy of ESDM for peripheral nerve injuries. However, given the large number of variables related to ES and the heterogeneity in disease etiologies and clinical manifestations, future studies on homogeneous populations using different stimulation protocols may be useful. [ABSTRACT FROM AUTHOR]

Peripheral nerve injuries are among those complicated medical conditions, which are still waiting for their highly effective first‐line therapies. In this study, the role of Calotropis procera crude leaves was evaluated at different doses for their effectiveness in improving functional recovery following sciatic nerve injury‐induced in the mouse model. Thirty‐two healthy albino mice were divided into four groups as Normal chow group (control, n = 8) and C. procera chow groups (50 mg/kg (n = 8), 100 mg/kg (n = 8) and 200 mg/kg (n = 8)). Behavioral analyses were performed to assess and compare improved functional recovery along with skeletal muscle mass measurement in all groups. Serum samples were analyzed for oxidative stress markers. Results showed that C. procera leaves at dose‐dependent manner showed statistically prominent (p <.05) increase in sensorimotor functions reclamation as confirmed by behavioral analyses along with muscle mass restoration and prominent decline in TOS and momentous increase in TAC along with the augmented activity of antioxidative enzymes. [ABSTRACT FROM AUTHOR]

Surgical intervention is required to successfully treat severe, large‐gap (≥4 cm) peripheral nerve injuries. However, all existing treatments have shortcomings and an alternative to the use of autologous nerves is needed. Human and porcine nerves are physiologically similar, with comparable dimensions and architecture, presence and distribution of Schwann cells, and conserved features of the extracellular matrix (ECM). We report the repair of fully transected radial nerves in 10 Rhesus Macaques using viable, whole sciatic nerve from genetically engineered (GalT‐KO), designated pathogen free (DPF) porcine donors. This resulted in the regeneration of the transected nerve, and importantly, recovery of wrist extension function, distal muscle reinnervation, and recovery of nerve conduction velocities and compound muscle action potentials similar to autologous controls. We also demonstrate the absence of immune rejection, systemic porcine cell migration, and detectable residual porcine material. Our preliminary findings support the safety and efficacy of viable porcine nerve transplants, suggest the interchangeable therapeutic use of cross‐species cells, and highlight the broader clinical potential of xenotransplantation. [ABSTRACT FROM AUTHOR]

Peripheral nerve injuries (PNI/s) are common orthopedic conditions, characterized by motor and sensory deficits in the damaged region. There is growing evidence that the L‐type calcium channel antagonist nimodipine has neuroprotective and neuroregenerative effects in animal models of neurological disorders. The efficacy of nimodipine on improving motor function and sensation following a sciatic nerve crush model was investigated in male Wistar rats as a model of PNI. At different time periods following damage, we evaluated motor function, sensory recovery, electrophysiology, histomorphometry, and gene expression. Moreover, we used histological and mass ratio analysis of the gastrocnemius muscle to assess atrophy. Our findings suggest that the nimodipine improves motor and sensory function more quickly in the damaged region 2, 4, and 6 weeks after 1 week of treatment. Nimodipine treatment also increased the number of myelinated fibers while decreasing their thickness, as shown by histomorphometry. Additionally, nimodipine treatment increases the mRNA levels of neurotrophic factors (BDNF and NGF), which are known to contribute to the regeneration of injured neurons. The impact of nimodipine in PNI recovery may be due to its stimulation of the CREB signaling pathway and suppression of pro‐inflammatory factor production. [ABSTRACT FROM AUTHOR]

Due to the limited self‐repairing capacity after peripheral nerve injuries (PNI), artificial nerve conduits are widely applied to facilitate neural regeneration. Exogenous electrical stimulation (ES) that is carried out by the conductive conduit regulates the biological behavior of Schwann cells (SCs). Meanwhile, a longitudinal surface structure counts to guide axonal growth to accelerate the end‐to‐end connection. Currently, there are no conduits equipped with both electrical conduction and axon‐guiding surface structure. Herein, a biodegradable, conductive poly(l‐lactide‐co‐caprolactone)/graphene (PLCL/GN) composite conduit is designed. The conduit with 20.96 ± 1.26 MPa tensile strength has a micropatterned surface of 20 µm groove fabricated by microimprint technology and self‐assembled polydopamine (PDA). In vitro evaluation shows that the conduits with ES effectively stimulate the directional cell migration, adhesion, and elongation, and enhance neuronal expression of SCs. The rat sciatic nerve crush model demonstrates that the conductive micropatterned conduit with ES promotes the growth of myelin sheath, faster nerve regeneration, and 20‐fold functional recovery in vivo. These discoveries prove that the PLCL(G)/PDA/GN composite conduit is a promising tool for PNI treatment by providing the functional integration of physical guidance, biomimetic biological regulation, and bioelectrical stimulation, which inspires a novel therapeutic approach for nerve regeneration in the future. [ABSTRACT FROM AUTHOR]

Objective: Head trauma can be a cause of refractory olfactory dysfunction due to olfactory nervous system injury. Anti‐inflammatory treatment using steroids or anti‐cytokine agents is known to contribute to functional recovery of the central and peripheral nervous systems in injury models, while there is a concern that they can induce adverse reactions. The present study examines if high‐dose immunoglobulin G (IgG) can facilitate olfactory functional recovery following injury. Methods: Olfactory nerve transection (NTx) was performed in OMP‐tau‐lacZ mice to establish injury models. High‐dose IgG was intraperitoneally injected immediately after the NTx and histological assessment of recovery within the olfactory bulb was performed at 5, 14, 42, and 100 days after the drug injection. X‐gal staining labeled degenerating and regenerating olfactory nerve fibers and immunohistochemical staining detected the presence of reactive astrocytes and macrophages/microglia. Olfactory function was assessed using an olfactory avoidance behavioral test. Results: High‐dose IgG‐injected mice showed significantly smaller areas of injury‐associated tissue, fewer astrocytes and macrophages/microglia, and an increase in regenerating nerve fibers. An olfactory avoidance behavioral test showed improved functional recovery in the IgG‐injected mice. Interpretation: These findings suggest that high‐dose IgG could provide a new therapeutic strategy for the treatment of olfactory dysfunction following head injuries. [ABSTRACT FROM AUTHOR]

Terminal Schwann cells (SCs) are nonmyelinating glia that are a prominent component of the neuromuscular junction (NMJ) where motor neurons form synapses onto muscle fibers. These cells play important roles not only in development and maintenance of the neuromuscular synapse but also restoring synaptic function after nerve damage. In response to muscle denervation, terminal SCs undergo dramatic changes in their gene expression patterns as well as in their morphology, such as extending elaborate processes into inter‐junctional space. These SC processes serve as a path to guide axon terminal sprouts from nearby innervated junctions, promoting rapid reinnervation of denervated fibers. We studied the role of terminal SCs in synapse reformation by using two different fluorescent proteins to simultaneously label motor axons and SCs; we examined these junctions repeatedly in living animals using a fluorescence microscope. Here, we show that alterations in the patterns of muscle innervation following recovery from nerve injury can be explained by SC guidance of regenerating axons. In turn, this guidance leads to remodeling of the NMJ itself. By guiding axon growth in inter‐synaptic, retrograde, then, anterograde way, Schwann cells play an important role for rapid reinnervation of denervated synaptic sites to maintain muscle functionality and prevent paralysis following nerve injury or death of motor neurons. This causes changes in muscle innervation pattern and remodeling of synaptic sites. [ABSTRACT FROM AUTHOR]

Background: Persistent phrenic nerve palsy (PNP) is an established complication of atrial fibrillation (AF) ablation, especially during cryoballoon and thoracoscopic ablation. Data on persistent PNP reversibility is limited because most patients recover <24 h. This study aims to investigate persistent PNP recovery, freedom of PNP‐related symptoms after AF ablation and identify baseline variables associated with the occurrence and early PNP recovery in a large nationwide registry study. Methods: In this study, we used data from the Netherlands Heart Registration, comprising data from 9549 catheter and thoracoscopic AF ablations performed in 2016 and 2017. PNP data was available of 7433 procedures, and additional follow‐up data were collected for patients who developed persistent PNP. Results: Overall, the mean age was 62 ± 10 years, and 67.7% were male. Fifty‐four (0.7%) patients developed persistent PNP and follow‐up was available in 44 (81.5%) patients. PNP incidence was 0.07%, 0.29%, 1.41%, and 1.25%, respectively for patients treated with conventional‐RF, phased‐RF, cryoballoon, and thoracoscopic ablation respectively. Seventy‐one percent of the patients fully recovered, and 86% were free of PNP‐related symptoms after a median follow‐up of 203 (113–351) and 184 (82–359) days, respectively. Female sex, cryoballoon, and thoracoscopic ablation were associated with a higher risk to develop PNP. Patients with PNP recovering ≤180 days had a larger left atrium volume index than those with late or no recovery. Conclusion: After AF ablation, persistent PNP recovers in the majority of patients, and most are free of symptoms. Female patients and patients treated with cryoballoon or thoracoscopic ablation are more prone to develop PNP. [ABSTRACT FROM AUTHOR]

Complex regional pain syndrome is a painful and debilitating syndrome in which the patient presents with disabling pain, edema, and/or vasomotor or sudomotor abnormalities. The mechanism is complex and not well understood. There is no definitive treatment for the condition yet. Pulsed radiofrequency is a minimally invasive, minimal destructive, and safe intervention. It can be used for neuropathic pain. A 40‐year‐old man with complex regional pain syndrome complained of intractable pain of the lower limb secondary to injury to the saphenous nerve due to a third‐degree burn. Conventional medications, epidural block, and sympathetic nerve block provided temporary relief. We performed pulsed radiofrequency of the saphenous nerve for the management of lower limb pain, and the symptoms remained under control at 3 months. To the best of our knowledge, this is the first application of ultrasound‐guided pulsed radiofrequency of the saphenous nerve for the management of complex regional pain syndrome. [ABSTRACT FROM AUTHOR]

CRPS is a type of severe pain syndrome and can be triggered by previous surgery or trauma. CRPS involves vasomotor changes such as changes in color and temperature of the skin, edema, increased sensitivity to touch, and a limited range of movement. Depending on the presence of nerve damage, CRPS is divided into two types. CRPS type II is associated with a confirmed peripheral nerve injury, while CRPS type I is not associated with an apparent peripheral nerve injury. Despite the ongoing therapy, sometimes, patients still have persistent, burning pain. Intractable CRPS that fail more conservative treatments may undergo neuromodulation. We want to present to your attention a case report of the successful treatment of a patient with CRPS type II using epidural unilateral stimulation. The 44‐year‐old woman came to us with complaints of burning pain and numbness of 1–3 fingers of the right hand, the lateral surface of the right wrist, and lower quarter of the forearm, and shooting pain in the projection of the right median nerve from the shoulder to the wrist. A clinical diagnosis was made—CRPS type II. During the stimulation trial, the most effective pain relief was obtained when the electrode was located in the right side of epidural space at the C4‐Th1 level. The implantation of a pulse generator was performed, and the final selection of the stimulation parameters was carried out (Pulse width: 60 ms, Rate: 210 Hz, and Amplitude: 0.9–1.6 V). The severity of pain syndrome was measured using validated scales in the preoperative period (VAS: 8–9, Pain Detect: 22, NTSS‐9: 4.62, and DN4: 8), in the early postoperative period (VAS: 0–1, Pain Detect: 6, NTSS −9: 0.66, and DN4: 1), and after 12 months (VAS: 0–2, Pain Detect: 6, NTSS‐9: 0.99, and DN4: 1). Observation during 12 months showed that a stable analgesic effect of neurostimulation was achieved using standard neuromodulation regimens and the adaptive stim option. Unilateral stimulation is an effective type of SCS in the treatment of pain syndromes. adaptive stim is usually not applicable for lead implantation at the cervical level. Nevertheless, the rational use of stimulation at threshold values allowed our patient to use adaptive stim in a non‐standard situation. [ABSTRACT FROM AUTHOR]

Dental pulp stem cells (DPSCs) which are derived from the neural crest are promising tools in stem cell therapy in the clinic. However, they tend to lose their multi‐lineage potency spontaneously during long‐term expansion in vitro. A micropattern‐based system is developed to train DPSCs with 1024 µm2 and aspect ratios of 1:2 and 1:4, which enhances their stemness and differentiation potential. This mechanical memory induced by micropattern would also rescue the pluripotency of long‐term expansion DPSCs. Micropatterns remodel the cytoskeleton and nuclear morphology, soften the cells, and induce the mitochondria into an immature state. Micropattern also activates extracellular related kinase, signal transducer, and activator of transcription 3, and inhibits Yes‐associated protein nuclear localization to enhance the stemness of DPSCs. In vivo implantation proves that DPSCs mechanically trained by micropattern could promote nerve regeneration in rats with peripheral nerve injury. A micropattern‐based approach is provided as a stem cell gym that absents exogenous growth factors to enhance the stemness and regenerative properties of DPSCs. It may shed light on future stem cell therapy. [ABSTRACT FROM AUTHOR]

Cold intolerance and pain can be a substantial problem in patients with peripheral nerve injury. We aimed at investigating the relationships among sensory recovery, cold intolerance, and neuropathic pain in patients affected by upper limb peripheral nerve injury (Sunderland type V) treated with microsurgical repair, followed by early sensory re‐education. In a cross‐sectional clinical study, 100 patients (male/female 81/19; age 40.5 ± 14.8 years and follow‐up 17 ± 5 months, mean ± SD), with microsurgical nerve repair and reconstruction in the upper extremity and subsequent early sensory re‐education, were evaluated, using Cold Intolerance Symptoms Severity questionnaire‐Italian version (CISS‐it, cut‐off pathology >30/100 points), CISS questionnaire‐12 item version (CISS‐12, 0‐46 points‐grouping: healthy that means no cold intolerance [0‐14], mild [15‐24], moderate [25‐34], severe [35‐42], very severe [43‐46] cold intolerance), probability of neuropathic pain (DouleurNeuropathique‐4; [DN4] 4/10), deep and superficial sensibility, tactile threshold (monofilaments), and two‐point discrimination (cutoff S2; Medical Research Council scale for sensory function; [MRC‐scale]). A high CISS score is associated with possible neuropathic pain (DN4 ≥ 4). Both a low CISS‐it score (ie, < 30) and DN4 < 4 is associated with good sensory recovery (MRC ≥ 2). In conclusion patients affected by upper limb peripheral nerve injuries with higher CISS scores more often suffer from cold intolerance and neuropathic pain, and the better their sensory recovery is, the less likely they are to suffer from cold intolerance and neuropathic pain. [ABSTRACT FROM AUTHOR]

Peripheral nerve injury is a challenging orthopedic condition that can be treated by autograft transplantation, a gold standard treatment in the current clinical setting. Nevertheless, limited availability of autografts and potential morbidities in donors hampers its widespread application. Bioactive scaffold‐based tissue engineering is a promising strategy to promote nerve regeneration. Additionally, magnesium (Mg) ions enhance nerve regeneration; however, an effectively controlled delivery vehicle is necessary to optimize their in vivo therapeutic effects. Herein, a bisphosphonate‐based injectable hydrogel exhibiting sustained Mg2+ delivery for peripheral nerve regeneration is developed. It is observed that Mg2+ promoted neurite outgrowth in a concentration‐dependent manner by activating the PI3K/Akt signaling pathway and Sema5b. Moreover, implantation of polycaprolactone (PCL) conduits filled with Mg2+‐releasing hydrogel in 10 mm nerve defects in rats significantly enhanced axon regeneration and remyelination at 12 weeks post‐operation compared to the controls (blank conduits or conduits filled with Mg2+‐absent hydrogel). Functional recovery analysis reveals enhanced reinnervation in the animals treated with the Mg2+‐releasing hydrogel compared to that in the control groups. In summary, the Mg2+‐releasing hydrogel combined with the 3D‐engineered PCL conduit promotes peripheral nerve regeneration and functional recovery. Thus, a new strategy to facilitate the repair of challenging peripheral nerve injuries is proposed. [ABSTRACT FROM AUTHOR]

After peripheral nerve injury, there are important changes at the spinal level that can lead to disorganization of the central circuitry and thus compromise functional recovery even if axons are able to successfully regenerate and reinnervate their target organs. Physical rehabilitation is a promising strategy to modulate these plastic changes and thus to improve functional recovery after the damage of the nervous system. Forced exercise in a treadmill is able to partially reverse the synaptic stripping and the loss of perineuronal nets that motoneurons suffer after peripheral nerve injury in animal models. The aim of this study was to investigate whether passive exercise, by means of cycling in a motorized bicycle, or voluntary free running in a wheel is able to mimic the effects induced by forced exercise on the changes that axotomized motoneurons suffer after peripheral nerve injury. Partial preservation of synapses and perineuronal nets was observed only in axotomized motoneurons from animals subjected to high-intensity cycling and the ones that freely ran long distances, but not when low-intensity exercise protocols were applied. Therefore, the intensity but not the type of exercise used is the key element to prevent synaptic stripping and loss of perineuronal nets in motoneurons after axotomy., (© 2017 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.)