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Objective: An altered sensation during endodontic treatment can occur due to the extrusion of endodontic materials. This study aims to discuss intentional replantation to address paresthesia resulting from an endodontic file penetrating the inferior alveolar nerve canal and provide a protocol for managing nerve injuries in such incidents. Case presentation: A 12-year-old girl developed paresthesia when an endodontic file separated and was inadvertently pushed through the apical foramen into the inferior alveolar nerve canal during root canal treatment of the mandibular left first molar. A CBCT scan revealed the file penetrating the canal towards the inferior border of the mandible. After considering the treatment options, intentional replantation was deemed suitable. The tooth was atraumatically extracted and preserved in sterile saline. The surgeon then carefully cleaned and irrigated the socket. The radiographic assessment confirmed successful file removal from the socket. The root ends were resected, and retrograde preparation and obturation were conducted using ultrasonic tips and mineral trioxide aggregate. The tooth was then replanted into the socket. Successful replantation was confirmed by tooth stability and an audible click. The patient was prescribed antibiotics and steroids. After completion of the endodontic treatment, a stainless steel crown was cemented. The successful intentional replantation procedure resulted in rapid improvement in the patient's condition. The normal sensation had been restored, indicating nerve recovery. At the 15-month follow-up, periapical bone healing and the eruption of the adjacent second molar were observed, affirming the treatment protocol's overall success. Conclusion: Prompt intervention and immediate intentional replantation facilitated direct inspection of the separated file within the socket. Collaboration between an oral maxillofacial surgeon and an endodontist ensures expedited and targeted treatment, leading to favorable outcomes. [ABSTRACT FROM AUTHOR]

Traumatic peripheral nerve injuries (PNI) are debilitating and can leave patients severely limited with drastic changes in quality of life. PNI treatment options are varied; however, only 50% of those patients regain any useful function. The complex intrinsic organisation of nerves is largely contribute to this issue. This research aimed at creating a reliable way of isolating and predicting the location of peripheral nerve fascicles on microscopic images of nerve cross-sections via semantic segmentation and machine learning. Using the Anaconda Python platform, a machine learning algorithm was programmed using a random forest classifier. Training data resulted in a 91% accuracy rate with respect to correctly identifying image pixels as fascicle or not. When the trained model was tested in the real world with unseen data, the results varied. However, the model retained the ability to identify fascicles and isolate them from background. The development of clinically successful PNI treatments has long been hindered by intrinsic nerve structures that machine learning may be able to solve. With further development, this research has the potential to expand and form new frontiers in the field of clinical medicine and drastically improve outcomes of PNI. [ABSTRACT FROM AUTHOR]

Background: Extracorporeal shock wave therapy (ESWT), as a non-invasive physical agent modality, was effective in relieving spasticity, reducing pain, and improving dysfunction. This systematic review and meta-analysis aimed to investigate the effect of ESWT on nerve conduction, and to find out whether the ESWT group is superior to the control or other comparison groups, thus providing support for guiding the rehabilitation of peripheral nerve injury in clinical work. Methods: PubMed, Web of Science, the Cochrane Library, and Embase were searched from inception to August 20, 2024. This review adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and registered in the PROSPERO database (registration number CRD42024500891). It aimed to compare (1) the ESWT group (ESWT) and baseline, and (2) subgroup analyses: ESWT and the control group (Control), ESWT and the local corticosteroid injection group (LCI), ESWT combined with physical therapy (ESWT + PT) and PT alone, and ESWT and PT. Outcome indicators extracted were nerve conduction study results: sensory nerve action potential (SNAP) amplitude, SNAP distal latency, sensory nerve conduction velocity (SNCV), compound muscle action potential (CMAP) amplitude, motor nerve distal latency (MNDL), motor nerve conduction velocity (MNCV), H/M ratio and H-reflex latency. Results: A total of 879 papers were identified through the database searches. Twenty-four trials were included in the systematic review, and 22 trials were included in the meta-analysis. The results showed that: (1) compared to the baseline, ESWT reduced SNAP distal latency mid-term (MD, −0.39; 95% CI: −0.52, −0.26; I 2 = 85%), and improved SNCV both short-term (MD, 4.36; 95% CI: 1.23, 7.49; I 2 = 91%) and mid-term (MD, 2.65; 95% CI: 1.79, 3.51; I 2 = 61%). At the same time, it reduced MNDL short-term (MD, −0.61; 95% CI: −0.91, −0.30; I 2 = 92%), but had no significant effect on MNCV. (2) Subgroup analyses showed that ESWT was superior to Control but not significantly better than LCI, especially in SNCV. The excitatory effect of ESWT + PT on the sensory and motor nerves was significantly better than that of PT alone. Conclusion: ESWT had some excitatory effect on peripheral nerves, especially on sensory nerve studies. Although the efficacy of this treatment was superior to that of the control group, and the combined treatment with PT was more effective than PT alone, its efficacy might not exceed that of LCI. Systematic review registration: Unique identifier: PROSPERO (CRD42024500891). [ABSTRACT FROM AUTHOR]

A majority of small-diameter dorsal root ganglion neurons die following traumatic nerve injury. Discrete subpopulations are differentially lost, with Mrgprd-expressing nonpeptidergic nociceptors particularly vulnerable. There is a rich literature describing the loss of dorsal root ganglion (DRG) neurons following peripheral axotomy, but the vulnerability of discrete subpopulations has not yet been characterised. Furthermore, the extent or even presence of neuron loss following injury has recently been challenged. In this study, we have used a range of transgenic recombinase driver mouse lines to genetically label molecularly defined subpopulations of DRG neurons and track their survival following traumatic nerve injury. We find that spared nerve injury leads to a marked loss of cells containing DRG volume and a concomitant loss of small-diameter DRG neurons. Neuron loss occurs unequally across subpopulations and is particularly prevalent in nonpeptidergic nociceptors, marked by expression of Mrgprd. We show that this subpopulation is almost entirely lost following spared nerve injury and severely depleted (by roughly 50%) following sciatic nerve crush. Finally, we used an in vitro model of DRG neuron survival to demonstrate that nonpeptidergic nociceptor loss is likely dependent on the absence of neurotrophic support. Together, these results profile the extent to which DRG neuron subpopulations can survive axotomy, with implications for our understanding of nerve injury–induced plasticity and pain. [ABSTRACT FROM AUTHOR]

Our group identified nucleus accumbens myocyte enhancer factor 2C as a targetable regulator of maladaptive behaviors and physiological changes after prolonged nerve injury. Supplemental Digital Content is Available in the Text. Preclinical and clinical work has demonstrated altered plasticity and activity in the nucleus accumbens (NAc) under chronic pain states, highlighting critical therapeutic avenues for the management of chronic pain conditions. In this study, we demonstrate that myocyte enhancer factor 2C (MEF2C), a master regulator of neuronal activity and plasticity, is repressed in NAc neurons after prolonged spared nerve injury (SNI). Viral-mediated overexpression of Mef2c in NAc neurons partially ameliorated sensory hypersensitivity and emotional behaviors in mice with SNI, while also altering transcriptional pathways associated with synaptic signaling. Mef2c overexpression also reversed SNI-induced potentiation of phasic dopamine release and neuronal hyperexcitability in the NAc. Transcriptional changes induced by Mef2c overexpression were different than those observed after desipramine treatment, suggesting a mechanism of action different from antidepressants. Overall, we show that interventions in MEF2C-regulated mechanisms in the NAc are sufficient to disrupt the maintenance of chronic pain states, providing potential new treatment avenues for neuropathic pain. [ABSTRACT FROM AUTHOR]

Background: Peripheral nerve injury is a challenging orthopedic issue in clinical management that often leads to limb dysfunction or even disability in severe cases. A thorough exploration of the repair process of peripheral nerve injury and the underlying mechanism contributes to formulate more effective therapeutic strategies. Methods: In the present study, we established a sciatic nerve transection injury model in Sprague-Dawley (SD) rats. A 12-week compensatory repair of sciatic nerve transection injury using a chitin cannula for small gap anastomosis was then performed via sleeve jointing the proximal common peroneal nerve to the distal tibial nerve and common peroneal nerve, with a 2 mm interval. Compensatory repair via small gap amplification was observed via gross observation of nerve specimen, osmic acid staining, and electrophysiological stimulation of sciatic nerve branches of the tibial and common peroneal nerve. Rat limbs were observed, and the functional recovery of effector muscles of the gastrocnemius and tibialis anterior muscles was assessed through weighing the muscle wet weight, Hematoxylin and Eosin (H&E) staining, and muscle strength detection. H&E staining, Masson staining, and toluidine blue staining were performed to observe the morphological changes of the dorsal root ganglion. Positive expressions of key proteins involved in the Phosphatase and tensin homologue deleted on chromosome ten (PTEN)-protein kinase B (AKT)/mammalian target of rapamycin (mTOR) signaling pathway, including PTEN, AKT, mTOR, Toll-like receptor 4 (TLR4), and Caspase9 in the dorsal root ganglion during compensatory repair of sciatic nerve after injury via small gap amplification, were detected by immunohistochemical staining. Results: It is found that the compensatory repair of sciatic nerve transection injury using a chitin cannula for small gap anastomosis via sleeve jointing effectively restored the continuity, number of myelinated nerve fibers, and nerve conduction velocity. It promoted toe abduction recovery, improved muscle fiber morphology and increased the wet weight and muscle strength of the gastrocnemius muscle and tibialis anterior muscle. Moreover, it increased the number of neurons and nerve fibers, and improved their morphology. Downregulated PTEN, TLR4, and Caspase9 in the dorsal root ganglia and upregulated AKT and mTOR were observed after small gap amplification than those of the transection injury group, which were closer to those of the control group. Conclusions: Compensatory repair of sciatic nerve transection injury using a chitin cannula for small gap anastomosis via sleeve jointing can restore the morphology and function of the sciatic nerve, effector muscles, and corresponding dorsal root ganglia by activating the PTEN-AKT/mTOR signaling pathway in the dorsal root ganglia. Our findings provide novel therapeutic targets for peripheral nerve injuries. [ABSTRACT FROM AUTHOR]

Peripheral nerve injury may result in muscle atrophy and impaired motor function recovery, and numerous pieces of evidence indicate that long noncoding RNAs (lncRNAs) play crucial roles in skeletal muscle regeneration. Our preliminary sequencing results showed that LNC_000280 was significantly down-regulated in denervated mouse skeletal muscle and we hypothesized that LNC_000280 may play an important role in skeletal muscle regeneration. In this research, flow cytometry and EdU staining results showed that overexpression of LNC_000280 promoted the proliferation of C2C12, while knockdown LNC_000280 had the opposite effect. Knockdown LNC_000280 inhibited the differentiation of C2C12 cells. LNC_000280 regulated the expression of proliferation genes (Cdk2, Cdc27) and differentiation genes (MyoG, MyoD). GO analysis and PPI network of LNC_000280 target genes showed that LNC_000280 mainly regulates skeletal muscle cell metabolism, mitochondrial and muscle growth. Idh2, Klhl31, Agt, and Gpt2 may be important downstream targets for its function. Therefore, we believe that that LNC_000280 can regulate the proliferation and differentiation of myoblasts by regulating gene expression. [ABSTRACT FROM AUTHOR]

With the rapid progress of industrialization, the incidence of peripheral nerve injuries caused by trauma has been continuously increasing. These injuries result in a significant number of disabilities and irreversible functional impairments, not only severely impacting the health and quality of life of patients but also placing a heavy economic burden on families and society. Effectively promoting peripheral nerve regeneration has thus become a key focus and challenge in current research. In recent years, hybrid biohydrogels with adhesive properties have gained widespread attention due to their excellent biocompatibility, mechanical stability, conductivity, and biodegradability. These materials can provide an optimal microenvironment to promote neuron adhesion and axonal extension while offering outstanding mechanical strength to meet the fixation requirements in clinical surgeries. This paper systematically reviews the application of adhesive hybrid biohydrogels in peripheral nerve injury repair, highlighting the latest research progress in promoting nerve regeneration and improving functional recovery, and discusses the challenges and future prospects for their clinical application. [ABSTRACT FROM AUTHOR]

Background and Aims Methods Results Interpretation Peripheral nerve injuries often require bridging when direct repair is not feasible. Nerve autografts are the gold standard, but they can lead to donor site morbidity. Silk fibroin‐based nerve conduits, like the novel SILKBridge, offer a promising alternative. This pilot study evaluates the mid‐term outcomes of the first in‐human digital nerve reconstruction using the SILKBridge, focusing on sensory recovery, complication rates, patient‐reported outcomes, and biological integration.This study included four patients with digital nerve defects reconstructed using the SILKBridge. Clinical assessments included two‐point discrimination, Semmes–Weinstein monofilament testing, and pain evaluation using the Numeric Rating Scale. Sonographic assessments were also performed to evaluate the conduit's biointegration and potential complications.At a mean follow‐up of 32 months, all patients demonstrated satisfactory sensory recovery and reported minimal to no pain. Sonographic assessments confirmed effective biointegration with no signs of inflammation or scarring.The mid‐term evaluation of the first in‐human digital nerve reconstruction with the SILKBridge revealed safety, efficiency, and favorable biocompatibility properties. Further studies with larger cohorts are needed to validate these findings and compare them with other nerve repair methods. [ABSTRACT FROM AUTHOR]

Background Aim Study Design Results Relevance to Clinical Practice Prone positioning improves oxygenation in adults with acute respiratory distress syndrome (ARDS) and has been extensively applied in intensive care units (ICU) during the COVID‐19 pandemic. Although some complications due to the manoeuvre are well known, brachial plexus injury after prone positioning is reported as a rare complication and the phenomenon could be either very rare or underestimated.This study aimed to evaluate the effect of swimmer position during prone ventilation on the onset of brachial plexus injury in patients admitted to ICU for ARDS. The study will also evaluate the safety of prolonged prone positioning collecting data on any adverse events occurred.A prospective, observational cohort study will be conducted in a tertiary level ICU in the metropolitan area of Milano (Italy) specialized in advanced treatment of patients with ARDS. This observational study will report clinical data on the electromyography (EMG) and the muscle strength assessment, including comorbidities and cardio‐respiratory status. A baseline EMG will be performed within 2 h from the first pronation manoeuvre and immediately at the end of each pronation cycle. The functional assessment of patients will be also performed at the end of ICU stay and at hospital discharge.The primary outcome is to estimate the prevalence of brachial plexus injury in patients with ARDS placed in the swimmer position during prone ventilation. Secondary outcomes will also include the safety of the manoeuvre by evaluation of all adverse events classified as skin or ocular damage, loss of tube and vascular access and new pressure ulcers.The findings of this study will contribute to understand the possible benefits/harms of prone ventilation performed using swimmer position. Eventually, this will call for the development of specific and tailored rehabilitation programs for patients with upper limb injuries during ICU stay, including also timely follow‐up upon ICU‐discharge. [ABSTRACT FROM AUTHOR]

Improved treatment options are urgently needed for neurological injuries resulting from trauma or iatrogenic events causing long-term disabilities that severely impact patients' quality of life. In vitro and animal studies have provided promising proof-of-concept examples of regenerative therapies using mesenchymal stromal cells (MSC) for a wide range of pathological conditions. Over the previous decade, various MSC-based therapies have been investigated in clinical trials to treat traumatic neurological injuries. However, while the safety and feasibility of MSC treatments has been established, the patient outcomes in these studies have not demonstrated significant success in the translation of MSC regenerative therapy for the treatment of human brain and spinal cord injuries. Herein, we have reviewed the literature and ongoing registered trials on the application of MSC for the treatment of traumatic brain injury, traumatic spinal cord injury, and peripheral nerve injury. We have focused on the shortcomings and technological hurdles that must be overcome to further advance clinical research to phase 3 trials, and we discuss recent advancements that represent potential solutions to these obstacles to progress. [ABSTRACT FROM AUTHOR]

Traumatic peripheral nerve injury (TPNI) is quite common in various types of acral trauma. It mostly passes unnoticed at the time of the initial trauma. The patients are usually sent for an ultrasound (US) assessment about 4 weeks following the trauma, after the electrophysiological changes are established. This paper presents a 5‐year experience of US findings of TPNI through 60 cases, who were examined as an outpatient with clinical and electrodiagnostic (EDX) tests suggesting nerve injury. The study population includes 40 males, 20 females, and mean age 34.4 ± 16.3. Upper limb nerves were more affected than the lower ones, with no significant difference between the right and left sides. Mechanisms of injury include laceration in 53.4% of cases, 38.3% had history of traction injury and only 8.3% had history of compression/contusion injury. Regarding the severity grading of the injuries, long segments of thickened separate or matted fascicles (Grades I and II) was found in 27 (40.9%) nerves; partial disruption with interstitial neuroma (Grade III) in 15 (22.7%) nerves; complete disruption (neurotmesis) (Grade IV) in 24 (36.4%) case. The integrity of six repaired nerves was also assessed. Muscle states within the territory of the motor nerve were always assessed, 62.9% of cases had decreased muscle bulk, 28.6% had muscle atrophy, and the remaining was normal. EDX testing results of 44 out of 60 patients was severe in 14 cases (31.8%), moderate in 15 cases (34.1%), mild in 11 case (25%), and normal in four cases (9.1%). The purpose of this study is to demonstrate that the US is a convenient neuroimaging tool by which we can accurately determine the level and the degree of peripheral nerve damage to plan the appropriate treatment. [ABSTRACT FROM AUTHOR]

Peripheral nerve injury significantly impairs sensory and motor functions, leading to diminished quality of life. Traditional treatments like nerve suturing and grafting often have limited efficacy and require long recovery. Recent advances in electrical stimulation technology show promise in speeding nerve repair, but current devices usually require lengthy surgeries, risking secondary nerve injury from prolonged nerve exposure during electrode installation and removal. This study introduces a portable, absorbable electrical stimulation system (PAESS) that integrates a battery‐free, wirelessly powered flexible printed circuit board chip with a biodegradable organic electrode. PAESS enables multiple self‐administered nerve stimulation without the need for electrode installation or removal. Using animal models, its electrical performance, biocompatibility, and efficacy in nerve repair are evaluated. The findings indicate a considerable enhancement in the recovery of nerve function, as demonstrated by improved electrophysiological measurements, decreased muscle atrophy, and positive histological results. Transcriptomic analysis indicates that the PAESS initiates the nerve regeneration process. This research presents an innovative platform for electrical stimulation, laying the groundwork for exploring electrical parameters and their mechanisms. This may deepen understanding of nerve regeneration and foster innovation in therapies. [ABSTRACT FROM AUTHOR]

Background: Peripheral nerve injuries (PNIs) are associated with significant physical and psychological challenges, impacting both functional recovery and quality of life. Despite the physical focus of traditional treatments, psychological factors play a crucial role in the outcomes of PNI repair and recovery. Objectives: This systematic review aims to evaluate the impact of psychological and social factors on the repair and recovery of peripheral nerve injuries. Methods: A comprehensive literature search was conducted in PubMed/Medline, EMBASE, and Cochrane databases, covering studies from January 1985 to December 2022. A total of 36,190 records were identified, and after screening with Rayyan AI and applying inclusion criteria, 111 articles were selected for review. Results: The review highlights that pre-existing psychological conditions, as well as psychological responses to the injury and treatment, significantly influence recovery outcomes in PNI patients. Psychological interventions, when integrated into standard care, may improve functional recovery and quality of life. Conclusions: Psychosocial factors are critical in the management of PNIs and should be incorporated into treatment algorithms to enhance patient outcomes. Future research should focus on developing and integrating psychological support strategies in PNI treatment protocols. [ABSTRACT FROM AUTHOR]

Tau is a microtubule-associated protein that plays a vital role in the mammalian nervous system. Alternative splicing of the MAPT gene leads to the formation of tau isoforms with varying N-terminal inserts and microtubule-binding repeats. Dysregulation of tau alternative splicing has been linked to diseases in the central nervous system, but the roles of tau isoforms in the peripheral nervous system remain unclear. Here, we investigated the alternative splicing of tau exons 4A and 10 in the sciatic nerve and Schwann cells during development and following injury. We discovered that low-molecular-weight (LMW) tau, resulting from the exclusion of exon 4A, and 3R tau, generated by the exclusion of exon 10, diminishes with aging in rat sciatic nerve and Schwann cells. High-molecular-weight (HMW) tau and 3R tau increase in the adult sciatic nerve post-injury. We constructed viruses that expressed HMW−4R, LMW−4R, HMW−3R, and LMW−3R and introduced them into cultured cells or the distal part of the injured sciatic nerve to assess their effects on Schwann cell migration and proliferation. We also examined the effects of the four isoforms on axon growth and debris clearance after sciatic nerve injury. Our results demonstrated that tau isoforms inhibit Schwann cell proliferation while promoting Schwann cell migration and sciatic nerve regeneration. Specifically, the 3R−tau isoforms were more effective than the 4R−tau isoforms in promoting nerve regeneration. In conclusion, our study reveals the roles of tau isoforms in the peripheral nervous system and provides insights into the development of new therapeutic strategies for peripheral nerve injuries. [ABSTRACT FROM AUTHOR]

The synaptic connections between dorsal root ganglia (DRG) and dorsal horn (DH) neurons are a crucial relay point for the transmission of painful stimuli. To delineate how synaptic plasticity may modulate the excitability of DH neurons, we have devised a microfluidic co-culture model that recapitulates the first sensory synapse using postnatal mouse sensory neurons. We show that DRG-DH co-cultures characterize salient features of the in vivo physiology of sensory neurons. Immunocytcochemical experiments of the cultured DH neurons show a co-localization of Map2 with VGlut2 and of Map2 with Synapsin 1, corroborating the glutamatergic identity of the DH neurons and further suggesting the potential formation of active synapses in this neuronal set. Fluorometric imaging experiments demonstrate the elicitation of calcium responses in DH neurons following the stimulation of DRG cell bodies or axons. Selective NMDA and AMPA receptor blockade appreciably silences DH neuron responses, suggesting that glutamatergic signaling is maintained in vitro. Last, a surrogate model of peripheral nerve injury is introduced in the form of an axotomy, which results in elevated and prolonged calcium responses of DH neurons. Overall, the microfluidic mouse co-cultures provide a method advancement in the study of periphery-to-center pain signaling, where the potential of utilizing the platform for drug target identification is underscored. [ABSTRACT FROM AUTHOR]

Recent studies have demonstrated a possible association between cognitive impairments and traumatic upper limb injuries. This study aims to track the cognitive changes in individuals with such injuries. In this longitudinal study, 36 participants with traumatic upper limb injuries and 36 uninjured participants were enrolled. Cognitive functions were assessed using the Rey Auditory Verbal Learning Test (RAVLT) and the Stroop Color and Word Test (SCWT) over a period of 6 months, with evaluations conducted on three occasions: 1 month (T1), 3 months (T2), and 6 months (T3). The results revealed that participants with nerve injuries exhibited significantly lower RAVLT scores overall and at each time point (Overall: Wald χ2 = 7.99, P < .05; T1: Wald χ2 = 7.61, P < .05; T2: Wald χ2 = 5.95, P < .05; T3: Wald χ2 = 5.76, P < .05). In contrast, no significant impairment in RAVLT performance was observed in participants without nerve injuries. Additionally, the SCWT showed no significant differences between injured and uninjured participants over the six-month period (P > .05). In conclusion, traumatic nerve injuries to the upper limbs negatively affect memory, and this impairment does not spontaneously recover within six months. [ABSTRACT FROM AUTHOR]

Background: Facial nerve baroparesis is a peripheral facial nerve injury resulting from barotrauma during activities such as diving, aviation, and mountain climbing. This condition occurs when increased pressure in the middle ear affects the facial nerve, leading to facial palsy. Despite being documented in otolaryngology literature, facial nerve baroparesis remains underreported and often misunderstood. Enhanced awareness and education about this condition are essential for effectively managing affected patients, helping to mitigate unnecessary panic and procedures during episodes. Case presentation: We present two cases of facial nerve baroparesis that occurred during flights. The first case involves a 25-year-old Arab male with no significant medical history who experienced a transient, one-time episode of right-sided facial nerve baroparesis during a flight from Kuwait to Syria; he reported nasal congestion and a sore throat prior to the flight, with the episode lasting approximately 30 min before resolving spontaneously. The second case is a 30-year-old Arab female with a history of chronic allergic rhinitis, who has experienced recurrent episodes of left-sided facial nerve baroparesis for the past 2 years, occurring during nearly every flight; each episode lasted around 5 min, caused severe facial pain, and also resolved spontaneously. Both patients exhibited varying degrees of Eustachian tube dysfunction. Treatment for the recurrent case included maneuvers to alleviate ear pressure and the use of nasal decongestants, which improved symptoms and decreased the frequency of episodes. Conclusion: Facial nerve baroparesis is frequently underestimated due to its temporary nature, yet it remains a significant cause of facial nerve palsy, especially after changes in pressure. Although the underlying mechanisms are not completely understood, dysfunction of the Eustachian tube is believed to be a contributing factor. Identifying the characteristic features of baroparesis—such as rapid onset, brief duration, and bilateral involvement of facial muscles—is essential for effective management. This highlights the necessity of educating healthcare professionals and flight personnel about this condition to prevent unnecessary treatments. For recurrent cases, management strategies should focus on alleviating Eustachian tube dysfunction. [ABSTRACT FROM AUTHOR]

• Comprehensively synthesize the functional features of OECs. • The function and mechanism of OECs in the repair of peripheral nerve injury were discussed. • Application of OECs in the treatment of pathological pain induced by peripheral nerve injury was discussed. Direct or indirect injury of peripheral nerve can lead to sensory and motor dysfunction, which can lead to pathological pain and seriously affect the quality of life and psychosomatic health of patients. While the internal repair function of the body after peripheral nerve injury is limited. Nerve regeneration is the key factor hindering the recovery of nerve function. At present, there is no effective treatment. Therefore, more and more attention have been paid to the development of foreground treatment to achieve functional recovery after peripheral nerve injury, including relief of pathological pain. Cell transplantation strategy is a therapeutic method with development potential in recent years, which can exert endogenous alternative repair by transplanting exogenous functional bioactive cells to the site of nerve injury. Olfactory ensheathing cells (OECs) are a special kind of glial cells, which have the characteristics of continuous renewal and survival. The mechanisms of promoting nerve regeneration and functional repair and relieving pathological pain by transplantation of OECs to peripheral nerve injury include secretion of a variety of neurotrophic factors, axonal regeneration and myelination, immune regulation, anti-inflammation, neuroprotection, promotion of vascular growth and improvement of inflammatory microenvironment around nerve injury. Different studies have shown that OECs combined with biomaterials have made some progress in the treatment of peripheral nerve injury and pathological pain. These biomaterials enhance the therapeutic effect of OECs. Therefore, the functional role of OECs in peripheral nerve injury and pathological pain was discussed in this paper. Although OECs are in the primary stage of exploration in the repair of peripheral nerve injury and the application of pain, but OECs transplantation may become a prospective therapeutic strategy for the treatment of peripheral nerve injury and pathological pain. [ABSTRACT FROM AUTHOR]

Animal models of peripheral nerve injury (PNI) serve as the fundamental basis for the investigations of nerve injury, regeneration, and neuropathic pain. The injury properties of such models, including the intensity and duration, significantly influence the subsequent pathological changes, pain development, and therapeutic efficacy. However, precise control over the intensity and duration of nerve injury remains challenging within existing animal models, thereby impeding accurate and comparative assessments of relevant cases. Here, a new model that provides quantitative and off‐body controllable injury properties via a magnetically controlled clamp, is presented. The clamp can be implanted onto the rat sciatic nerve and exert varying degrees of compression under the control of an external magnetic field. It is demonstrated that this model can accurately simulate various degrees of pathology of human patients by adjusting the magnetic control and reveal specific pathological changes resulting from intensity heterogeneity that are challenging to detect previously. The controllability and quantifiability of this model may significantly reduce the uncertainty of central response and inter‐experimenter variability, facilitating precise investigations into nerve injury, regeneration, and pain mechanisms. [ABSTRACT FROM AUTHOR]

Peripheral neuropathic pain is common in patients with peripheral nerve injury and can significantly impact both their function and quality of life. There is a wide variety of non‐interventional treatment approaches, including pharmacologic therapy, physical/occupational therapy, modalities (therapeutic, mechanical, thermal, etc.), psychology, and lifestyle modification. First line pharmacologic therapy for peripheral neuropathic pain includes gabapentinoids, tricyclic antidepressants, and serotonin‐norepinephrine reuptake inhibitors. Other classes of medications, such as topical treatments, opioids, and cannabinoids, have more limited usefulness in treatment but remain part of a treatment regimen. Physical and occupational therapy, psychological interventions, and lifestyle medicine are important adjuncts in the treatment and prevention of future peripheral neuropathic pain. The strength of the evidence supporting each intervention varies, with that for pharmacologic intervention being the strongest. A combination of these options tailored to the individual needs of the patient likely will result in the best treatment outcome for peripheral neuropathic pain. [ABSTRACT FROM AUTHOR]

The transcription repressor REST in the dorsal root ganglion (DRG) is upregulated by peripheral nerve injury and promotes the development of chronic pain. However, the genes targeted by REST in neuropathic pain development remain unclear. The expression levels of four opioid receptor genes (Oprm1, Oprd1, Oprl1 and Oprk1) and the cannabinoid CB1 receptor (Cnr1) gene in the DRG regulate nociception. In this study, we determined the role of REST in controlling their expression in the DRG induced by spared nerve injury (SNI). SNI induced chronic pain hypersensitivity in wild-type mice and was accompanied by increased levels of Rest transcript and protein. Transcriptomic analyses of wild-type mouse DRGs suggested that SNI upregulates the expression of Rest transcripts and downregulates the transcripts of all four opioid receptor genes and the Cnr1 gene. Quantitative reverse transcription polymerase chain reaction analyses of these tissues validated these results. Analysis of publicly available bioinformatic data suggested that REST binds to the promoter regions of Oprm1 and Cnr1. Chromatin immunoprecipitation analyses indicated the presence of REST at these promoters. Full-length Rest conditional knockout in primary sensory neurons reduced SNI-induced pain hypersensitivity and rescued the SNI-induced reduction in the expression of Oprd1 and Cnr1 in mouse DRG. Our results suggest that nerve injury represses the transcription of at least the Oprd1 and Cnr1 genes via REST in primary sensory neurons and that REST is a potential therapeutic target for neuropathic pain. Thus, inhibiting REST activity could potentially reduce chronic neuropathic pain and augment opioid/cannabinoid analgesic actions by increasing the transcription of Oprd1 and Cnr1 genes in DRG neurons. [ABSTRACT FROM AUTHOR]

Peripheral nerve injuries (PNIs) are common, costly, and cause significant pain. Effective management of PNIs involves tailoring medications to the injury type as well as understanding the pharmacokinetics/pharmacodynamics to support nerve regeneration and reduce pain. Opioids act on opioid receptors to significantly reduce pain for many patients, but there are significant addiction risks and side effects. In addition, opioids may exacerbate pain sensitivity and affect nerve regeneration. Non‐steroidal anti‐inflammatory drugs or acetaminophen act on cyclooxygenase enzymes and are commonly used for nerve pain, with 34.7% of people using them for neuropathic pain. While effective for mild pain, they are often combined with opioids, gamma‐aminobutyric acid (GABA) analogs, lidocaine, or corticosteroids for more severe pain. Corticosteroids, mimicking adrenal hormones like cortisol, treat PNI‐related inflammation and pain. Their pharmacokinetics are complex, often requiring local injections in order to minimize systemic risks while effectively treating PNIs. Lidocaine, a common local anesthetic, blocks ion channels in the central nervous system (CNS) and peripheral nerves, providing strong analgesic and anti‐inflammatory effects. If used improperly, lidocaine can cause neuronal toxicity instead of anesthetic effect. GABA acts as an inhibitory neurotransmitter in the CNS and its drug analogs like pregabalin and gabapentin can alleviate neuropathic pain by binding to voltage‐gated Ca2+ channels, inhibiting neurotransmitter release. These pain medications are commonly prescribed for PNIs despite a limited guidance on their effects on nerve regeneration. This review will discuss these drug's mechanisms of action, pharmacokinetics/pharmacodynamics, and their clinical application to highlight their effect on the PNI recovery. [ABSTRACT FROM AUTHOR]

Injury to the peripheral nervous system disconnects targets to the central nervous system, disrupts signal transmission, and results in functional disability. Although surgical and therapeutic treatments improve nerve regeneration, it is generally hard to achieve fully functional recovery after severe peripheral nerve injury. A better understanding of pathological changes after peripheral nerve injury helps the development of promising treatments for nerve regeneration. Single-cell analyses of the peripheral nervous system under physiological and injury conditions define the diversity of cells in peripheral nerves and reveal cell-specific injury responses. Herein, we review recent findings on the single-cell transcriptome status in the dorsal root ganglia and peripheral nerves following peripheral nerve injury, identify the cell heterogeneity of peripheral nerves, and delineate changes in injured peripheral nerves, especially molecular changes in neurons, glial cells, and immune cells. Cell-cell interactions in peripheral nerves are also characterized based on ligand-receptor pairs from coordinated gene expressions. The understanding of cellular changes following peripheral nerve injury at a single-cell resolution offers a comprehensive and insightful view for the peripheral nerve repair process, provides an important basis for the exploration of the key regulators of neuronal growth and microenvironment reconstruction, and benefits the development of novel therapeutic drugs for the treatment of peripheral nerve injury. [ABSTRACT FROM AUTHOR]

Introduction: Ferroptosis is a new type of cell death characterized by lipid peroxidation and iron dependency, representing an emerging disease regulation mechanism. The limited understanding of ferroptosis in peripheral nerve injury (PNI) complicates the management of such injuries. Mitochondrial dysfunction, which contributes to ferroptosis, further exacerbates the challenges of peripheral nerve repair Methods: In this study, we established an in vitro model of Schwann cells model treated with TBHP and an in vivo sciatic nerve crush injury model in rats. These models were used to investigate the effects of fibroblast growth factor 21 (FGF21) on PNI, both in vitro and in vivo, and to explore the potential mechanisms linking injury-induced ferroptosis and mitochondrial dysfunction. Results: Our findings reveal that PNI triggers abnormal accumulation of lipid reactive oxygen species (ROS) and inactivates mitochondrial respiratory chain complex III, leading to mitochondrial dysfunction. This dysfunction catalyzes the oxidation of excessive polyunsaturated fatty acids, resulting in antioxidant imbalance and loss of ferroptosis suppressor protein 1 (FSP1), which drives lipid peroxidation. Additionally, irregular iron metabolism, defective mitophagy, and other factors contribute to the induction of ferroptosis. Importantly, we found that FGF21 attenuates the abnormal accumulation of lipid ROS, restores mitochondrial function, and suppresses ferroptosis, thus promoting PNI repair. Notably, glutathione peroxidase 4 (GPX4), a downstream target of nuclear factor E2-related factor 2 (Nrf2), and the ERK/Nrf2 pathway are involved in the regulation of ferroptosis by FGF21. Conclusion: FGF21 promotes peripheral nerve repair by inhibiting ferroptosis caused by mitochondrial dysfunction. Therefore, targeting mitochondria and ferroptosis represents a promising therapeutic strategy for effective PNI repair. [ABSTRACT FROM AUTHOR]

Peripheral nerve damage can cause debilitating symptoms ranging from numbness and pain to sensory loss and atrophy. To uncover the underlying mechanisms of peripheral nerve injury, our research aims to develop a relationship between biomechanical peripheral nerve damage and function through finite element modeling. A noncontact, ex vivo electrophysiology chamber, capable of axially stretching explanted nerves while recording electrical signals, was used to investigate peripheral nerve injury. Successive stretch trials were run on eight sciatic nerves (four females and four males) excised from Sprague–Dawley rats. Nerves were stretched until 50% compound action potential (CAP) amplitude reduction was obtained. A constitutive model developed by Raghavan and Vorp was suitable for rat sciatic nerves, with an average α and β of 0.183 MPa and 1.88 MPa, respectively. We then generated 95% confidence intervals for the stretch at which specific CAP amplitude reductions would occur, which compares well to previous studies. We also developed a finite element model that can predict stretch‐induced signaling deficits, applicable for complex nerve geometries and injuries. This relationship between nerve biomechanics and function can be expanded upon to create a clinical model for peripheral nerve dysfunction due to stretch. [ABSTRACT FROM AUTHOR]

Purpose: The objective of this study was to determine the incidence, necessity for neurosurgical intervention, and overall results of the treatment of pediatric peripheral nerve injuries associated with dislocated supracondylar fractures of the distal humerus. Method: A retrospective analysis of pediatric patients with supracondylar fractures treated from April 2019 to April 2022 with a minimum follow-up of 3 months was conducted. Results: Of 453 included patients, there were 51 recorded peripheral nerve injuries. The ulnar nerve was the most frequently injured nerve. Nine patients required neurosurgical intervention, with the most common procedure being the release of entrapped nerves. The combination of a supracondylar fracture and arterial injury was identified as a significant risk factor for peripheral nerve injury (p < 0.001). Only one patient experienced an unsatisfactory outcome. Conclusion: Although the prognosis for peripheral nerve injuries in children with supracondylar fractures is generally favorable, these injuries must be properly identified. We recommend an active neurosurgical approach in children with persisting neurological deficits to minimize the risk of permanent neurological impairment. [ABSTRACT FROM AUTHOR]

Background: Muscle atrophy caused by denervation is common in neuromuscular diseases, leading to loss of muscle mass and function. However, a comprehensive understanding of the overall molecular network changes during muscle denervation atrophy is still deficient, hindering the development of effective treatments. Method: In this study, a sciatic nerve transection model was employed in male C57BL/6 J mice to induce muscle denervation atrophy. Gastrocnemius muscles were harvested at 3 days, 2 weeks, and 4 weeks post-denervation for transcriptomic and proteomic analysis. An integrative multi-omics approach was utilized to identify key genes essential for disease progression. Targeted proteomics using PRM was then employed to validate the differential expression of central genes. Combine single-nucleus sequencing results to observe the expression levels of PRM-validated genes in different cell types within muscle tissue.Through upstream regulatory analysis, NRF2 was identified as a potential therapeutic target. The therapeutic potential of the NRF2-targeting drug Omaveloxolone was evaluated in the mouse model. Result: This research examined the temporal alterations in transcripts and proteins during muscle atrophy subsequent to denervation. A comprehensive analysis identified 54,534 transcripts and 3,218 proteins, of which 23,282 transcripts and 1,852 proteins exhibited statistically significant changes at 3 days, 2 weeks, and 4 weeks post-denervation. Utilizing multi-omics approaches, 30 hubgenes were selected, and PRM validation confirmed significant expression variances in 23 genes. The findings highlighted the involvement of mitochondrial dysfunction, oxidative stress, and metabolic disturbances in the pathogenesis of muscle atrophy, with a pronounced impact on type II muscle fibers, particularly type IIb fibers. The potential therapeutic benefits of Omaveloxolone in mitigating oxidative stress and preserving mitochondrial morphology were confirmed, thereby presenting novel strategies for addressing muscle atrophy induced by denervation. GSEA analysis results show that Autophagy, glutathione metabolism, and PPAR signaling pathways are significantly upregulated, while inflammation-related and neurodegenerative disease-related pathways are significantly inhibited in the Omaveloxolone group.GSR expression and the GSH/GSSG ratio were significantly higher in the Omaveloxolone group compared to the control group, while MuSK expression was significantly lower than in the control group. Conclusion: In our study, we revealed the crucial role of oxidative stress, glucose metabolism, and mitochondrial dysfunction in denervation-induced muscle atrophy, identifying NRF2 as a potential therapeutic target. Omaveloxolone was shown to stabilize mitochondrial function, enhance antioxidant capacity, and protect neuromuscular junctions, thereby offering promising therapeutic potential for treating denervation-induced muscle atrophy. [ABSTRACT FROM AUTHOR]

Microglia take on an altered morphology during chronic opioid treatment. This morphological change is broadly used to identify the activated microglial state associated with opioid side effects, including tolerance and opioid-induced hyperalgesia (OIH). Microglia display similar morphological responses in the spinal cord after peripheral nerve injury (PNI). Consistent with this observation, functional studies have suggested that microglia activated by opioids or PNI engage common molecular mechanisms to induce hypersensitivity. In this article, we conducted deep RNA sequencing (RNA-seq) and morphological analysis of spinal cord microglia in male mice to comprehensively interrogate transcriptional states and mechanistic commonality between multiple models of OIH and PNI. After PNI, we identify an early proliferative transcriptional event across models that precedes the upregulation of histological markers of microglial activation. However, we found no proliferative transcriptional response associated with opioid-induced microglial activation, consistent with histological data, indicating that the number of microglia remains stable during morphine treatment, whereas their morphological response differs from PNI models. Collectively, these results establish the diversity of pain-associated microglial transcriptomic responses and point towards the targeting of distinct insult-specific microglial responses to treat OIH, PNI, or other central nervous system pathologies. [ABSTRACT FROM AUTHOR]