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Cerclage wiring may be used to optimize the stability of intramedullary nail or plate fixations in comminuted proximal femoral fractures, periprosthetic fractures, and other selected cases. In this article, we presented a novel case of iatrogenic sciatic nerve entrapment from cerclage wiring used to supplement intramedullary nail fixation. We also illustrate and highlight the role of ultrasound in assessing the sciatic nerve to make a timely diagnosis. [ABSTRACT FROM AUTHOR]

Periacetabular osteotomy includes a fluoroscopy-guided ischial cut without direct visualization. Previously described techniques include a mediolateral ischial cortex cut, which is associated with the risk of injuring nearby nerves. Another drawback of that technique is the difficulty connecting an ischial cortex cut with a retroacetabular cut due to orthogonal nature of the osteotomy. In general, an additional cut from medial to lateral is required. The present study aimed to describe a technique that eliminates those problems due to use of only a central cut of the ischium and the curved nature of the osteotomy. [ABSTRACT FROM AUTHOR]

Background: In nerve transfer for peripheral nerve injury, it is sometimes necessary to suture size-mismatched nerves. In 1993, a favorable suture method called the Ochiai suture method for size-mismatched nerve transfer was reported. However, there is currently a lack of substantial evidence beyond the original report. Therefore, this study aimed to verify the advantages of using the Ochiai suture method for size-mismatched nerve transfer. Methods: A total of 18 rats were evaluated in this study and randomly divided into two groups. All rats underwent femoral to sciatic nerve transfer. Specifically, group A (n = 10) underwent the Ochiai suture method, while group B (n = 8) underwent the perineural suture method. After 12 weeks postoperatively, we conducted the sciatic functional index (SFI) test, measured muscle wet-weight, and performed histological evaluations. All data were compared between the two groups, with Welch's t test for normally distributed data and Mann-Whitney's U test for non-normally distributed data. Statistical significance was set at p < 0.05. Results: The mean number of axons was significantly greater in group A than in group B at 5 mm distal to the stump (p = 0.04). Additionally, the average axonal diameter was significantly greater in group A than in group B at 5 mm and 10 mm distal to the stump (p < 0.01 and p < 0.01, respectively). However, the SFI test and measured muscle wet-weight values showed no significant differences between the two groups. Conclusions: Our study revealed that the Ochiai suture method for size-mismatched nerve transfer in rats increases the regenerative axon numbers and diameters. These findings suggest that the Ochiai suture method could be a valuable approach for achieving effective motor function restoration in cases of size-mismatched nerve transfer. [ABSTRACT FROM AUTHOR]

Background: There is a long latent period for the sciatic nerve block before a satisfactory block is attained. Changes in the temperature of local anesthetics may influence the characters of the peripheral nerve block. This study was designed to evaluate the effect of warming ropivacaine on the ultrasound-guided subgluteal sciatic nerve block. Methods: Fifty-four patients for distal lower limbs surgery were randomly allocated into warming group (group W, n = 27) or room tempeture group (group R, n = 27) with the ultrasound-guided subgluteal sciatic nerve block. The group W received 30 ml of ropivacaine 0.5% at 30℃ and the group R received 30 ml of ropivacaine 0.5% at 23℃. The sensory and motor blockade were assessed every 2 min for 30 min after injection. The primary outcome was the onset time of limb sensory blockade. Results: The onset time of sensory blockade was shorter in group W than in group R (16 (16,18) min vs 22 (20,23) min, p < 0.001), and the onset time of motor blockade was also shorter in group W than in group R (22 (20,24) min vs 26 (24,28) min, p < 0.001). The onset time of sensory blockade for each nerve was shorter in group W than in group R (p < 0.001). No obvious differences for the duration of sensory and motor blockade and the patient satisfaction were discovered between both groups. No complications associated with nerve block were observed 2 days after surgery. Conclusions: Warming ropivacaine 0.5% to 30℃ accelerates the onset time of sensory and motor blockade in the ultrasound-guided subgluteal sciatic nerve block and it has no influence on the duration of sensory and motor blockade. Trial registration: The trial was registered on October 3, 2022 in the Chinese Clinical Trial Registry (https://www.chictr.org.cn/bin/project/edit?pid=181104), registration number ChiCTR2200064350 (03/10/2022). [ABSTRACT FROM AUTHOR]

Background & Aims: Pain is divided into two main types, fast and slow. Pain receptors are composed of free nerve endings and use two separate pathways to transmit pain signals to the CNS. Sharp pain signals are produced by mechanical and thermal pain stimuli. These signals are transmitted to the spinal cord by peripheral nerves through Aδ fibers at a speed of 3-15 m/s. On the contrary, slow and chronic pain signals are mainly produced by chemical pain stimuli, but sometimes stable mechanical or thermal stimuli can also produce these signals. These signals are transmitted to the spinal cord by C-type fibers at a speed of 0.5 to 2 m/s (1). The mechanisms of neuropathic pain are not fully known, but the mechanisms proposed in the pathogenesis of this pain include the role of glial cells as supporting cells of the central nervous system, changes in sodium and potassium voltage-dependent channels, afferents adjacent to the neuron. It is damaged. Different neural pathways are affected differently. Therefore, identification of these pathways is important in determining the analgesic and medicinal mechanisms from physiological aspects. Although there are many studies in this field, one of the existing problems is the rate of recovery and return of nerve activity after injury. The results of researchers' research have brought relatively acceptable results, which were not without problems. In the present research, due to the high incidence of peripheral nerve injuries caused by blows and fractures in humans and animals, efforts will be made to find a drug or drug combination to accelerate the healing process of damaged nerves following experimental sciatic nerve injury in the rat animal model. Therefore, the present study will be conducted in order to investigate the analgesic effects of simvastatin and its neurophysiological interaction with the involved systems following experimental sciatic nerve ligation in rats. Methods: This research was used in 2 experimental phases on 85 adult male rats weighing 180-200 grams. These animals were transferred to the laboratory animal breeding and maintenance center of the veterinary school and were kept in standard mouse cages under standard conditions. All animals were evaluated for motor health before surgery, and then all mice were anesthetized by intraperitoneal injection of ketamine hydrochloride (60 mg/kg) and xylazine (10 mg/kg), and after scrubbing and initial leg preparation The animals were placed on their left side and an incision was made in the posterior-external skin of the thigh area of the left leg. The muscles and fascia were gently removed and after exposing the sciatic nerve, the sciatic nerve was compressed for 60 seconds using a micro hemostat. In order to trace, the injury site is marked by suturing the muscle closest to the crush site using non-absorbable silk suture (0-5) and then the muscles are placed together and the subcutaneous tissue and skin are The sequence was stitched using vicryl thread (0-4) and nylon (0-3) in a simple all round and single stitch method. Then formalin test was done and licking time was measured. The animals were divided into 4 groups: group 1: nerve damage without treatment, group 2, 3 and 4 were treated with simvastatin. Mice in group 2 (with a dose of 2 mg/kg), group 3 (with a dose of 4 mg/kg) and group 4 (with a dose of 8 mg/kg) were treated with Sivastatin. There were 5 mice in each group and they were evaluated in two time intervals of 2 and 4 weeks. Results: As seen in Figure 1, the injection of morphine (5 mg/kg) significantly reduced the pain time caused by the formalin test compared to the control group (P<0.05). The level of 4 and 8 mg/kg simvastatin significantly decreased the pain time caused by the formalin test compared to the control group (P<0.05). According to the results of the statistical analysis of repeated measurements of one factor, the summary of the analysis of variance of the changes in the duration of the animal's response to the stimulating effects of formalin affected by the effective dose (8 mg/kg) of simvastatin compared to naloxone during the acute and chronic phases is presented in Figure 2. Naloxone injection (2 mg/kg) had no effect on pain time caused by formalin test compared to the control group (P>0.05). The level of 8 mg/kg simvastatin significantly decreased the pain time caused by the formalin test compared to the control group (P<0.05). The combined injection of naloxone plus simvastatin significantly reduced the analgesic effects of simvastatin compared to the simvastatin alone group (P<0.05). According to the results of the statistical analysis of the repeated measurements of one factor, the summary of the analysis of variance of the changes in the duration of the animal's response to the stimulating effects of formalin affected by the effective dose (8 mg/kg) of simvastatin compared to speroheptadine during the acute and chronic phases is presented in Figure 3. According to the results of the statistical analysis of the repeated measurements of one factor, the summary of the analysis of variance of the changes in the duration of the animal's response to the stimulating effects of formalin affected by the effective dose (8 mg/kg) of simvastatin compared to cimetidine during the acute and chronic phases is presented in graph No. 4 . Conclusion: The aim of this study is the analgesic effects of simvastatin following experimental sciatic nerve ligation in rats. According to the obtained results, it was determined that the analgesic effects of simvastatin are dose-dependent and the findings of this test show that the effective dose (8 mg/kg) of simvastatin alone has been able to create a significant effect in reducing the painful effects of formalin in animals. It has also caused a significant decrease in the response time to formalin pain stimulus in animals. Antagonists naloxone, cyproheptadine and cimetidine were able to inhibit the analgesic effects in acute and chronic phase. Simvastatin activates the PI3K/AKt pathway and increases neurogenesis through BDNF and (Vascular endothelial growth factor) (12). Simvastatin increases the phosphorylation and expression of BDNF and VEGF gene in (Dentate gyrus) DG. As a result, cell proliferation increases and differentiation occurs in the DG area and brain recovery increases (14). Therefore, simvastatin may cause gene expression of growth factors, production of protein kinases, and subsequent induction of neurogenesis in the DG of the hippocampus, increasing dendritic branches through the activation of AKt through the signaling pathway (15). The effects of simvastatin on ischemia-reperfusion injury of the sciatic nerve in adult rats, as a result, administration of simvastatin before ischemia shows protective properties in nerve re-injury and improves blood supply again (16). [ABSTRACT FROM AUTHOR]

This study investigated changes in neurotransmitters induced by the application of electroacupuncture (EA) at Zusanli (ST36) and Neiguan (PC6). A total of 30 rats were divided into five groups: sham, ST (EA at bilateral ST36 and ST37), ScT (ST plus previous neurectomy of the bilateral sciatic nerves), ScS (sham plus previous neurectomy of the bilateral sciatic nerve), and PC (EA at bilateral PC6 and PC7). The P2X2 receptor expression was stronger in the sham group than in the ST and PC groups (both p < 0.05) but similar between the sham and ScT groups p > 0.05 . Dopamine levels in the extracellular fluid surrounding the acupoints were higher in the PC group than in the sham and ST groups during the postacupuncture period (both p < 0.05). Glutamate levels in the extracellular fluid surrounding the acupoints were higher in the ST group than in the sham group during the acupuncture period p < 0.05 and higher in the ST group than in the sham and PC groups during the postacupuncture period (both p < 0.05). Serum adrenaline and noradrenaline levels were higher in the PC group than in the sham, ST, and ScT groups (all p < 0.05). Glutamate levels in the CSF were higher in the ST group than in the sham, ScS, and PC groups (all p < 0.05). GABA levels in the CSF were higher in the ST group than in the sham, ScT, and PC groups (all p < 0.05). EA at ST36 and ST37 and PC6 and PC7 exerted an analgesic effect, EA at PC6 and PC7 can enhance heart function, and EA at ST36 and ST37 modulates the cerebral cortex. However, the study needs an evaluation of direct pain behavior, heart function, and brain function in the future. [ABSTRACT FROM AUTHOR]

Objective: To evaluate functional results after treatment of large defects of the sciatic nerve and its divisions by direct nerve suturing in high knee flexion. Methods: A retrospective review was conducted in patients treated for lower extremity nerve defects between 2011 and 2019. Inclusion criteria were a defect > 2 cm with a minimal follow-up period of 2 years for the sciatic nerve and 1 year for its divisions. Nerve defects were bridged by an end-to-end suture with the knee flexed at 90° for 6 weeks. Functional results were assessed based on the Medical Research Council's grading system. Results: Seventeen patients with a mean age of 27.6 years were included. They presented with seven sciatic nerve defects and ten division defects, including eight missile injuries. The mean time to surgery was 12.3 weeks and the mean nerve defect length was 5 cm. Overall, 21 nerve sutures were performed, with eight in the tibial distribution and 13 in the fibular distribution. Post-operatively, there was no significant knee stiffness related to the immobilization. The mean follow-up time was 24.5 months. Meaningful motor and sensory recovery were observed after 7 of 8 sutures in the tibial distribution and 11 of 13 sutures in the fibular distribution. A functional sural triceps muscle with protective sensibility of the sole was restored in all patients. There were no differences according to the injury mechanisms. Conclusion: Temporary knee flexion at 90° allows for direct coaptation of sciatic nerve defects up to 8 cm, with promising results no matter the level or mechanism of injury. [ABSTRACT FROM AUTHOR]

Persistent sciatic arteries are rare congenital abnormalities, with an incidence between.01-.6%. Whilst most patients with the pathology are asymptomatic during their younger years, up to 48% of patients will suffer aneurysmal degeneration of the persistent sciatic artery and present with claudication or lower limb ischaemia (from distal embolisation of mural thrombus). Due to the rare nature of persistent sciatic artery aneurysms, optimal management of the pathology is yet to be determined. Both endovascular and open techniques have been described in the management of this pathology, however hybrid management approaches are reported infrequently. The authors present a case of a persistent sciatic artery aneurysm successfully treated in a 69-year-old male utilising a hybrid approach with a femoropopliteal bypass (below knee), Amplatzer plug occlusion of the aneurysm and subsequent resection of the aneurysm. [ABSTRACT FROM AUTHOR]

Background: Peripheral nerve regeneration is a coordinated process of Schwann cell (SC) reprogramming and intrinsic neuronal growth program activation. Panaxydol (PND) is a strong biologically active traditional Chinese medicine monomer extracted from Panax notoginseng rhizomes. In vitro, PND protects neurons and SCs from injury and stimulates the expression and secretion of neurotrophic factors (NTFs) by SCs. We hypothesized that PND may also promote peripheral nerve regeneration in adult animals. Methods: PND (10 mg/kg body weight) was injected intraperitoneally into the Sprague--Dawley (SD) rats for two consecutive weeks after sciatic nerve transection. The morphology of the repaired sciatic nerve was evaluated after 16 weeks, and sensory and motor function recovery was evaluated using functional and behavioral techniques. Results: PND was biologically safe at an injection dose of 10 mg/kg/day. After 14 days, it significantly increased the myelination of regenerated nerve fibers, and promoted sensory and motor function recovery. In the early stage of injury, PND significantly upregulated the mRNA expression of brain-derived neurotrophic factor (BDNF) and its receptors in distal injured nerves, which may represent a possible mechanism by which PND promotes nerve regeneration in vivo. Conclusions: Our study demonstrated that PND leads to sensory and motor recovery in a sciatic nerve transection model rat. Furthermore, we showed that BDNF mRNA level was significantly increased in the injured distal nerve, potentially contributing to the functional recovery. Further research is warrantied to examine whether direct injection is a more efficient method to increase BDNF expression compared to an exogenous BDNF administration. [ABSTRACT FROM AUTHOR]

Objective: Complete resection is the curative treatment choice for recurrent gynecological malignancies. Laterally extended endopelvic resection (LEER) is an effective surgical salvage therapy for lateral recurrence. However, when a recurrent tumor occupies the ischial spine and sacrum, LEER is not indicated, and surgical salvage therapy is abandoned. Theoretically, complete resection of such a tumor is possible by additional pelvic bone resection along with the standard LEER. Nevertheless, owing to the anatomical complexities of the beyond-LEER procedure, 2 major issues should be solved: sciatic nerve injury and tumor disruption during pelvic bone amputation. To overcome these technical challenges, we applied a multidirectional beyond-LEER approach, a novel salvage surgical procedure, with an aim of demonstrating its technical feasibility., Methods: We created a simulation model of a laterally recurrent tumor that occupied the right ischial spine and sacrum in a Thiel-embalmed cadaver., Results: Multidirectional approaches, including laparoscopic, perineal, and dorsal phases, were safely applied. We laparoscopically marked the L4-L5-S1 complex and S2 nerve with different colored tapes, and by pulling them out into a dorsal surgical field, the sciatic nerve was safely preserved. The dissection lines of the multidirectional approaches were aligned using tapes as landmarks, and complete tumor clearance without tumor disruption was accomplished. By following the cadaveric training, the first laparoscopic-assisted beyond-LEER procedure was successfully performed in a patient with recurrent ovarian cancer., Conclusion: Using a Thiel-embalmed cadaver, we demonstrated the technical feasibility of a sciatic nerve-preserved beyond-LEER procedure, which was successfully performed in a patient with recurrent ovarian cancer., Competing Interests: No potential conflict of interest relevant to this article was reported., (© 2024. Asian Society of Gynecologic Oncology, Korean Society of Gynecologic Oncology, and Japan Society of Gynecologic Oncology.)

Background: Functional recovery following peripheral nerve injury worsens with increasing time of denervation before repair. Denervated muscle undergoes progressive atrophy that limits the extent to which motor endplates can be reinnervated. The aims of this study were to assess nerve injuries reconstructed at different time points and to identify various neural and muscle-based markers to predict functional outcome, including an in-depth look at the neuromuscular junction (NMJ)., Methods: Adult wild-type C57BL/6J mice underwent surgery on the sciatic nerve and were divided into 5 groups: (1) nerve cut and repaired, (2) acute (nerve cut and immediately repaired with a 1-cm autograft), (3) subacute (nerve grafted 2 weeks after injury), (4) delayed (nerve grafted 4 weeks after injury), (5) nerve cut and capped. Functional recovery was measured by treadmill and electrodiagnostic tests. Nerves were harvested for histologic evaluation, and leg muscles, for histologic evaluation and NMJ immunofluorescent staining of motor endplate innervation and terminal Schwann cells (tSCs)., Results: The delayed graft group performed worst in nearly all parameters. The subacute graft group shared more similarities with the acute group, especially the tSC response (subacute, 48%; acute, 51%) and motor endplate innervation pattern (subacute, 75%; acute, 72%). The only parameters to elucidate differences were muscle weight and motor endplate fragmentation. Traditional axon count failed to capture differences among the 3 groups., Conclusion: The tSC activity and NMJ innervation pattern can be used as predictive markers of functional recovery that capture differences among acute, subacute, and delayed nerve injuries., Clinical Relevance Statement: The tSC activity at the NMJ displayed by immunohistochemical methods can accurately reflect target muscle innervation over time. This can be used as a predictor of reinnervation when timing of nerve reconstruction is delayed, which can be a critically needed tool in clinical scenarios., (Copyright © 2023 by the American Society of Plastic Surgeons.)

Objective: To observe the possibility of hyper selective neurectomy (HSN) of triceps branches combined with partial neurotomy of S 2 nerve root for relieving spastic equinus foot., Methods: Anatomical studies were performed on 12 adult cadaveric specimens. The S 2 nerve root and its branches were exposed through the posterior approach. Located the site where S 2 joined the sciatic nerve and measured the distance to the median line and the vertical distance to the posterior superior iliac spine plane, and the S 2 nerve root here was confirmed to have given off branches of the pelvic splanchnic nerve, the pudendal nerve, and the posterior femoral cutaneous nerve. Between February 2023 and November 2023, 4 patients with spastic equinus foot were treated with HSN of muscle branches of soleus, gastrocnemius medial head and lateral head, and cut the branch where S 2 joined the sciatic nerve. There were 3 males and 1 female, the age ranged from 5 to 46 years, with a median of 26 years. The causes included traumatic brain injury in 2 cases, cerebral hemorrhage in 1 case, and cerebral palsy in 1 case. The disease duration ranged from 15 to 84 months, with a median of 40 months. The triceps muscle tone measured by modified Ashworth scale (MAC) before operation was grade 3 in 2 cases and grade 4 in 2 cases. The muscle strength measured by Daniels-Worthingham manual muscle test (MMT) was grade 2 in 1 case, grade 3 in 1 case, and 2 cases could not be accurately measured due to grade 4 muscle tone. The Holden walking function grading was used to evaluate lower limb function and all 4 patients were grade 2. After operation, triceps muscle tone, muscle strength, and lower limb function were evaluated by the above grading., Results: The distance between the location where S 2 joined the sciatic nerve and median line was (5.71±0.53) cm and the vertical distance between the location and posterior superior iliac spine plane was (6.66±0.86) cm. Before joining the sciatic nerve, the S 2 nerve root had given off branches of the pelvic splanchnic nerve, the pudendal nerve, and the posterior femoral cutaneous nerve. All the 4 patients successfully completed the operation, and the follow-up time was 4-13 months, with a median of 7.5 months. At last follow-up, the muscle tone of the patients decreased by 2-3 grades when compared with that before operation, and the muscle strength did not decrease when compared with that before operation. Holden walking function grading improved by 1-2 grades, and there was no postoperative hypoesthesia in the lower limbs., Conclusion: HSN of triceps branches combined with partial neurotomy of S 2 nerve root can relieve spastic equinus foot without damaging other sacral plexus nerves.

Background: While sciatic nerve injury has been described as a complication of acetabular fractures, iatrogenic nerve injury remains sparsely reported. This study aims to assess iatrogenic sciatic nerve injuries occurring during acetabular fracture surgery, tracking their neurological recovery and clinical outcomes, and investigating any correlation between recovery and the severity of neurologic injury to facilitate physicians in providing prediction of prognosis., Case Presentation: We present two cases of male patients, aged 56 and 22, who developed sciatic palsy due to iatrogenic nerve injury during acetabular fracture surgery. Iatrogenic sciatic nerve injury resulted from operatively treated acetabular fractures. Surgical exploration, involving internal fixation removal and nerve decompression, successfully alleviated symptoms in both cases postoperatively. At the latest follow-up, one patient achieved full recovery with excellent function, while the other exhibited residual deficits at the L5/S1 root level along with minimal pain., Conclusion: Sciatic nerve injury likely stemmed from reduction techniques and internal fixation procedures for the posterior column, particularly when performed with the hip flexed, thereby placing tension on the sciatic nerve. Our case reports underscore the significance of liberal utilization of electrophysiologic examinations and intraoperative monitoring for the prediction of prognosis. Surgical exploration, encompassing internal fixation removal and nerve decompression, represents an effective intervention for resolving sciatic palsy, encompassing both sensory neuropathy and motor symptoms., (© 2024 The Author(s). Orthopaedic Surgery published by Tianjin Hospital and John Wiley & Sons Australia, Ltd.)

Purpose: To evaluate the effects on peripheral neural regeneration of the end-to-side embracing repair technique compared to the autograft repair technique in Wistar rats., Methods: Fifteen male Wistar rats were divided into three groups with five animals each: denervated group (GD), autograft group (GA), and embracing group (EG). For the evaluation, the grasping test, electroneuromyography (ENMG), and muscle weight assessment were used., Results: Muscle weight assessment and ENMG did not show significant neural regeneration at the end of 12 weeks in the DG and GE groups, but only in GA. The grasping test showed an increase in strength between the surgery and the fourth week in all groups, and only the GA maintained this trend until the 12th week., Conclusions: The present study indicates that the neural regeneration observed in the end-to-side embracing neurorrhaphy technique, in the repair of segmental neural loss, is inferior to autograft repair in Wistar rats.

Peripheral nerve injuries are common, and full functional recovery after injury is achieved in only 10% of patients. The sympathetic nervous system plays many critical roles in maintaining bodily homeostasis, but it has rarely been studied in the context of peripheral nerve injury. The extent of postganglionic sympathetic neuronal functions in distal targets in the periphery is currently unclear. To better explore the role of sympathetic innervation of peripheral targets, a surgical "knock-out" model provides an alternative approach. Although this can be achieved chemically, chemical destruction of postganglionic sympathetic neurons can be nonspecific and dose-dependent. The use of a surgical lumbar sympathectomy in mice, once thought to be "virtually not practicable" in small animals, allows for specific targeting of postganglionic sympathetic neurons that innervate the hind limbs. This manuscript describes how to surgically remove the L2-L5 lumbar sympathetic ganglia from a mouse as a survival surgery, which reliably decreases the hind paw sweat response and the number of sympathetic axons in the sciatic nerve.

Photochemical sealing of a nerve wrap over the repair site isolates and optimizes the regenerating nerve microenvironment. To facilitate clinical adoption of the technology, we investigated photosealed autologous tissue in a rodent sciatic nerve transection and repair model. Rats underwent transection of the sciatic nerve with repair performed in three groups: standard microsurgical neurorrhaphy (SN) and photochemical sealing with a crosslinked human amnion (xHAM) or autologous vein. Functional recovery was assessed at four-week intervals using footprint analysis. Gastrocnemius muscle mass preservation, histology, and nerve histomorphometry were evaluated at 120 days. Nerves treated with a PTB-sealed autologous vein improved functional recovery at 120 days although the comparison between groups was not significantly different (SN: -58.4 +/- 10.9; XHAM: -57.9 +/- 8.7; Vein: -52.4 +/- 17.1). Good muscle mass preservation was observed in all groups, with no statistical differences between groups (SN: 69 +/- 7%; XHAM: 70 +/- 7%; Vein: 70 +/- 7%). Histomorphometry showed good axonal regeneration in all repair techniques. These results demonstrate that peripheral nerve repair using photosealed autologous veins produced regeneration at least equivalent to current gold-standard microsurgery. The use of autologous veins removes costs and foreign body concerns and would be readily available during surgery. This study illustrates a new repair method that could restore normal endoneurial homeostasis with minimal trauma following severe nerve injury.

Background/aim: In the literature, almost all of the nerve conduits proposed for obtaining better nerve recovery were applied as graft materials. In this study, we aimed to propose a new nerve conduit model with a flap pattern and evaluate the effect of a pedicled vascularized jejunal flap on nerve regeneration after wrapping it around a sciatic nerve., Materials and Methods: A total of 90 Wistar albino rats were randomly divided into nine groups with 10 rats in each. The first three groups constituted the control groups, whereas Groups 4-6 were the jejunum conduit (JC)-applied groups. A mucosa-resected JC (MRJC) was applied in Groups 7 and 8. Epineurial neurorrhaphy was performed in Groups 1, 4, and 7; repair with a nerve graft was applied in Groups 2, 5, and 8; and a 1-cm-long nerve defect was created in Groups 3, 6, and 9. After 2 months of follow-up, nerve regeneration was assessed by statistical analyses of the Sciatic Functional Index (SFI) and histopathological evaluation., Results: The MRJC groups had significantly better results in terms of SFI (p = 0.005). Statistical differences in axonal degeneration, axonal density, myelination, and disorganization were found between all control groups and MRJC groups (p = 0.022, p = 0.001, p = 0.001, and p = 0.039, respectively)., Conclusion: In this study, the feasibility of wrapping around the nerve repair zones of pedicled autologous flaps designed in a tubular fashion was observed in a small rat model. The findings must be further validated with larger animals before clinical testing., Competing Interests: Declaration of competing interest: None of the authors has a financial interest in any of the products, devices, or drugs mentioned in this manuscript., (© TÜBİTAK.)

Background: Acellular nerve allografts (ANAs) were developed to replace the autologous nerve grafts (ANGs) to fill the peripheral nerve defects. Poor vascularization relative to ANGs has been a limitation of application of ANAs., Methods: A total of 60 female Sprague-Dawley rats were assigned 3 groups. The rats in A group received ANGs, the rats in B group received ANAs, and the rats in C group were transplanted with ANA carrying endothelial cells (ANA + ECs). In the 1st, 2nd, 4th, and 12th postoperative weeks, 5 rats were selected from each group for evaluating sciatic function index (SFI), electrophysiology, maximum tetanic force recovery rate, tibialis anterior muscle weights recovery rate, and microvessel density. In the 12th postoperative week, the nerves were harvested and stained with toluidine blue and observed under an electron microscope to compare nerve fibers, myelin width, and G-ratio., Results: All the rats survived. In the first and second postoperative weeks, more microvessels were found in the ANA + EC group. In the 12th postoperative week, the nerve fibers were more numerous, and G-ratio was smaller in the C group compared with the B group. The compound muscle action potential and maximum tetanic force recovery rate in the tibialis anterior muscle in the C group were better than those in the B group in the 12th postoperative week. The A group showed better performances in electrophysiology, maximum tetanic force, muscle wet weight, and nerve regeneration., Conclusion: ANA + ECs can promote early angiogenesis, promoting nerve regeneration and neurological function recovery., Competing Interests: Conflicts of interest and sources of funding: Zhongshan Hospital, 2021ZSQN31., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Autologous nerve grafts have been considered the gold standard for peripheral nerve grafts. However, due to drawbacks such as functional loss in the donor area and a shortage of donor sources, nerve conduits are increasingly being considered as an alternative approach. Polymer materials have been widely studied as nerve repair materials due to their excellent processing performance. However, their limited biocompatibility has restricted further clinical applications. The epineurium is a natural extra-neural wrapping structure. After undergoing decellularization, the epineurium not only reduces immune rejection but also retains certain bioactive components. In this study, decellularized epineurium (DEP) derived from the sciatic nerve of mammals was prepared, and a bilayer nerve conduit was created by electrospinning a poly (l-lactide-co-ε-caprolactone) (PLCL) membrane layer onto the outer surface of the DEP. Components of the DEP were examined; the physical properties and biosafety of the bilayer nerve conduit were evaluated; and the functionality of the nerve conduit was evaluated in rats. The results demonstrate that the developed bilayer nerve conduit exhibits excellent biocompatibility and mechanical properties. Furthermore, this bilayer nerve conduit shows significantly superior therapeutic effects for sciatic nerve defects in rats compared to the pure PLCL nerve conduit. In conclusion, this research provides a novel strategy for the design of nerve regeneration materials and holds promising potential for further clinical translation., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Development of methods to accelerate nerve regeneration in peripheral nerve damage is important. Electroacupuncture is a new therapeutic method that combines traditional acupuncture with modern electrotherapy. Melatonin has been shown to reduce nerve damage. Objectives: In this study, we aimed to determine and compare the therapeutic effects of electroacupuncture and melatonin on rat sciatic nerve injury. Methods: A total of 56 adult male Wistar Albino rats were divided into four study groups with 14 animals in each group: intact control (group I), subcutaneous saline (group II), subcutaneous melatonin (group III), and electroacupuncture (group IV). Surgical procedure including unilateral (right) sciatic nerve injury was applied to groups II, III, and IV. Saline and melatonin started immediately after surgery for six weeks, while electroacupuncture was given two weeks after surgery for 3 weeks. Functional and histological assessments were used as outcome measurements. Results: Sciatic nerve damage caused a significant decrease in nerve conduction velocity. Both electroacupuncture treatment and melatonin treatment significantly increased the nerve conduction velocity. Both sciatic functional recovery and histological regeneration were faster in these treatment groups compared to the saline. However, no significant difference was observed between the two treatment groups. Conclusion: Electroacupuncture and melatonin are promising alternative treatment strategies for peripheral nerve damage and can be examined in detail in future studies. [ABSTRACT FROM AUTHOR]

Objective. To study the effect of pulsed radio frequency (PRF) on nerve repair and the expression of GFAP and GDNF in rats with neuropathic pain. Methods. Thirty SPF healthy SD rats were randomly divided into control group (Group C), PSNL group (partial ligation of sciatic nerve) + sham group (Group PS), and PSNL group (partial ligation of sciatic nerve) + PRF group (Group PR), with 10 rats in each group. In group C, the right sciatic nerve was exposed without ligation. In the PS group, the model of neuropathic pain was established by partial ligation of sciatic nerve. The mice in the PR group were treated with PRF after establishing the neuropathic pain model. The general behavior of rats during the treatment was observed. The mechanical and thermal hyperalgesia were measured before operation and 1, 3, 7, and 14 days after operation. The content of inflammatory factors in nerve tissue was detected by ELISA. The pathological condition of nerve tissue was observed by HE. The gene and protein changes of GFAP and GDNF in nerve tissue were determined by QRT PCR and Western blot. Results. Rats in the control group were free to move and in good condition. In the PS group, there were different degrees of claudication, weakness of the lower limbs, lateral toe valgus, nerve injury, and other behavioral changes. After the pulsed radiofrequency in the PR group, the above symptoms decreased gradually with the prolongation of the treatment time. The mechanical pain sensitivity and thermal allodynia of the PS group were reduced after the operation. The mechanical pain sensitivity and thermal pain sensitivity of the PR group gradually increased with the prolongation of the treatment time, and the 14 days were basically close to the control group. The levels of TNF-α and IL-6 in ELISA were significantly higher in the PS group than in the control group, and the content in the PR group was gradually reduced, which was close to the control group. HE staining showed that the sciatic nerve fibers disappeared, and the formation of nerve cavities was obvious in the 14-day PS group. The nerve fibers were found in the sciatic tissue of the PR group, and there was no obvious hemorrhagic edema and cell deformation. The expression of GFAP mRNA in the PS group was significantly higher than that in the control group and the PR group (p < 0.05), and the expression of GDNF was opposite (p < 0.05). The results of western blot showed that the expression of GFAP protein in the 14-day PS group was significantly higher than that in the control group. The expression of the PR group decreased compared with the control group, and the expression of GDNF was opposite (p < 0.05). Conclusion. Pulsed radiofrequency ablation can promote neurological repair, promote GDNF, and reduce the expression of GFAP in rats with neuropathic pain. [ABSTRACT FROM AUTHOR]

Background: Recent experimental studies using herbal extracts have shown the possibility of peripheral nerve regeneration. This study aimed to investigate the effects of herbal extracts on peripheral nerve regeneration in a rat sciatic nerve injury model. Methods: A total of 53 rats were randomly assigned to a control group or one of four experimental groups. In all rats, the sciatic nerve was completely severed and microscopic epineural end-to-end neurorrhaphy was performed. Normal saline (2 mL) was topically applied to the site of nerve repair in the control group, whereas four different herbal extracts – 2 mL each of Astragalus mongholicus Bunge, Coptis japonica (Thunb.) Makino, Aconitum carmichaelii Debeaux, or Paeonia lactiflora Pall. – were topically applied to the site of nerve repair in each experimental group. Nerve conduction studies were performed at an average of 11.9 weeks after the operation, and conduction velocity and proximal and distal amplitudes were measured. Biopsies were performed at an average of 13.2 weeks after the initial neurorrhaphy. The quality of nerve anastomosis and perineural adhesion to the surrounding soft tissues was macroscopically evaluated. The neuroma size at the site of the neurorrhaphy was microscopically measured, whereas the size of the scar tissue was evaluated relative to the diameter of the repaired nerve. Results: The nerve conduction study results showed the highest nerve conduction velocity in the experimental group that used the Coptis japonica (Thunb.) Makino extract and the highest proximal and distal amplitudes in the experimental group that used the Aconitum carmichaelii Debeaux extract. Macroscopic evaluations after the second operation showed that grade 2 perineural adhesion was found in 70.8% of rats. The mean neuroma size in the Coptis japonica (Thunb.) Makino, Aconitum carmichaelii Debeaux, and Paeonia lactiflora Pall. groups showed statistically significant decreases relative to the control group. The mean scar tissue formation index in the Paeonia lactiflora Pall. group showed a statistically significant decrease relative to the control group. Conclusions: The peripheral nerve regeneration effect of the herbal extracts was confirmed through decreased neuroma and scar tissue formation. [ABSTRACT FROM AUTHOR]

Category: Bunion; Midfoot/Forefoot Introduction/Purpose: Combined sciatic and saphenous nerve blocks are commonly used for pain management after lower extremity procedures. Liposomal bupivacaine (LB) is a formulation of the local anesthetic bupivacaine that gradually releases bupivacaine for prolonged periods of analgesia. The objective of this phase 3 multicenter, randomized, double-blind, active- controlled study (NCT04518462) was to evaluate the postoperative analgesic effect of combined sciatic and saphenous nerve blocks with LB with or without admixed bupivacaine hydrochloride (HCl) versus bupivacaine HCl alone in adults undergoing bunionectomy or other lower extremity procedures. Methods: This study enrolled 2 parallel cohorts: pharmacokinetics, pharmacodynamics, efficacy, and safety were assessed in cohort 1 (bunionectomy), and efficacy and safety were further assessed in cohort 2 (bunionectomy, other lower extremity procedures). Eligibility criteria included American Society of Anesthesiologists physical status classification ≤3 and body mass index ≥18 to < 40 kg/m2. Participants were randomized 1:1:1 to receive LB 266 mg admixed with saline (LB266), LB 266 mg admixed with bupivacaine HCl 50 mg (LB266-ADMIX), or bupivacaine HCl 100 mg (BUP100), administered as a combined sciatic and saphenous block. No additional regional blocks were administered. For 96 hours after surgery, rescue medication included nonsteroidal anti- inflammatory drugs and acetaminophen and escalation to opioids if necessary. The primary endpoint was the area under the curve (AUC) of the numerical rating scale (NRS) pain intensity scores 0-96 hours after surgery. Total postsurgical opioid consumption 0- 96 hours after surgery was a secondary endpoint. Results: In total, 119 participants were enrolled (LB266: n=40; LB266-ADMIX: n=41; BUP100: n=40). The least squares mean (LSM) AUC of the NRS pain intensity score was nonsignificantly lower 0-96 hours after surgery for LB266 versus BUP100 (LSM [standard error], 286.9 [32.9] vs 348.6 [34.4]; LSM difference vs BUP100, −61.7 [95% confidence interval (CI), −147.0, 23.6]; P=0.1564). LB266 pain intensity scores were significantly higher 6-18 hours after surgery but were significantly lower at 36-96 hours than BUP100 (Figure). Cumulative opioid consumption differences 0-96 hours after surgery for LB266 versus BUP100 were not significant (LSM [95% CI], 20.7 [13.5, 31.7] vs 19.8 [12.7, 31.0]; P=0.8857). Mirroring pain scores, opioid consumption with LB266 versus BUP100 was higher at 0-24 hours but lower 24-96 hours (Figure); adverse events were similar. Conclusion: Cumulative pain intensity and opioid consumption were not significantly different between the LB266 and BUP100 groups 0-96 hours after surgery; however, consistent with the known mechanism of LB, pain intensity scores were significantly lower with LB266 36-96 hours after surgery, and opioid consumption was significantly lower 24-96 hours after surgery. [ABSTRACT FROM AUTHOR]

Purpose: While many studies have been conducted on peripheral nerve regeneration, few have focused on strengthening the nerve autografts. This study hypothesized that adding autologous stromal vascular fraction (SVF) to a nerve autograft will improve nerve regeneration. The purpose of this study was to compare the results of nerve autograft with and without SVF. Methods: An adipose tissue sample was excised from the right inguinal region of female Wistar rats, and SVF was separated by centrifugation. The left sciatic nerve was resected at a length of 15 mm and the defect was bridged by a resected nerve autograft. We added SVF with collagen gel around the nerve autograft in the SVF group and added saline in the control group. At 12 weeks after surgery, the wet muscle weight, distal latency, and amplitude of the compound muscle action potential of the tibialis anterior were evaluated by the ratio of left and right sides. Sciatic functional index (SFI) was also evaluated. Results: The wet muscle weight was significantly better in the SVF group than in the control group. The results of distal latency, amplitude, and SFI were not significantly different between the two groups; however, these results tended to be better in the SVF group than in the control group. Conclusion: SVF added to artificial nerve grafts has been reported to promote axonal regeneration through secretion of angiogenic, neurotrophic, and anti-apoptotic factors. This study indicates that SVF may also be effective for nerve autografts and improve the clinical result of nerve autograft. [ABSTRACT FROM AUTHOR]

Background: Functional recovery following primary nerve repair of a transected nerve is often poor even with advanced microsurgical techniques. Recently, we developed a novel sciatic nerve transection method where end-to-end apposition of the nerve endings with minimal gap was performed with fibrin glue. We demonstrated that transected nerve repair with gluing results in optimal functional recovery with improved axonal neurofilament distribution profile compared to the end-to-end micro-suture repair. However, the impact of axonal misdirection and misalignment of nerve fascicles remains largely unknown in nerve-injury recovery. We addressed this issue using a novel nerve repair model with gluing.Methods: In our complete "Flip and Transection with Glue" model, the nerve was "first" transected to 40% of its width from each side and distal stump was transversely flipped, then 20 µL of fibrin glue was applied around the transection site and the central 20% nerve was completely transected before fibrin glue clotting. Mice were followed for 28 days with weekly assessment of sciatic function. Immunohistochemistry analysis of both sciatic nerves was performed for neurofilament distribution and angiogenesis. Tibialis anterior muscles were analyzed for atrophy and histomorphometry.Results: Functional recovery following misaligned repair remained persistently low throughout the postsurgical period. Immunohistochemistry of nerve sections revealed significantly increased aberrant axonal neurofilaments in injured and distal nerve segments compared to proximal segments. Increased aberrant neurofilament profiles in the injured and distal nerve segments were associated with significantly increased nerve blood-vessel density and branching index than in the proximal segment. Injured limbs had significant muscle atrophy, and muscle fiber distribution showed significantly increased numbers of smaller muscle fibers and decreased numbers of larger muscle fibers.Conclusions: These findings in a novel nerve transection mouse model with misaligned repair suggest that aberrant neurofilament distributions and axonal misdirections play an important role in functional recovery and muscle atrophy. [ABSTRACT FROM AUTHOR]

Despite the advances in tissue engineering approaches, reconstruction of long segmental peripheral nerve defects remains unsatisfactory. Although autologous grafts with proper fascicular complementation have shown meaningful functional recovery according to the Medical Research Council Classification (MRCC), the lack of donor nerve for such larger defect sizes (>30 mm) has been a serious clinical issue. Further clinical use of hollow nerve conduits is limited to bridging smaller segmental defects of denuded nerve ends (<30 mm). Recently, bioinspired multichannel nerve guidance conduits (NGCs) gained attention as autograft substitutes as they mimic the fascicular connective tissue microarchitecture in promoting aligned axonal outgrowth with desirable innervation for complete sensory and motor function restoration. This review outlines the hierarchical organization of nerve bundles and their significance in the sensory and motor functions of peripheral nerves. This review also emphasizes the major challenges in addressing the longer nerve defects with the role of fascicular arrangement in the multichannel nerve guidance conduits and the need for fascicular matching to accomplish complete functional restoration, especially in treating long segmental nerve defects. Further, currently available fabrication strategies in developing multichannel nerve conduits and their inconsistency in existing preclinical outcomes captured in this review would seed a new process in designing an ideal larger nerve conduit for peripheral nerve repair.

Increased demand in services, workforce pressures and continued financial constraints has resulted in a significant expansion in advanced clinical practice roles in the United Kingdom. This article will describe the personal experience of a perioperative Advanced Clinical Practitioner in the design and implementation of a training programme to achieve competence in ultrasound-guided lower limb peripheral nerve blockade. Three specific lower limb peripheral nerve blockade were included in the training programme, namely sciatic nerve block at the popliteal fossa, saphenous nerve block, and femoral nerve block. Key service drivers underpinning development, rationale for Advanced Clinical Practitioner involvement in lower limb peripheral nerve blockade and governance will also be discussed.

Purpose: The ideal number of sutures for epineural nerve repair is still unclear. Increased number of sutures increases secondary damage and inflammation to the nerve tissue, which negatively affects nerve regeneration. When the number of sutures decreases, the strength of the nerve repair site decreases and nerve endings are fringed, which also negatively affects nerve regeneration. Therefore, each additional suture is not only beneficial but also detrimental. The aim of this study was to find out the ideal number of sutures for nerve repair., Methods: Seventy rats were randomly divided into 5 groups. One of the groups was used as a control group, and right sciatic nerves of the rats in other 4 groups were repaired by using 2, 3, 4, or 6 epineural sutures, respectively, after nerve transection. Biomechanical assessment was performed on the nerves collected from these rats at 5 days of follow-up. Functional and histological analyses were evaluated after 12 weeks of follow-up., Results: It was found that an increase in the number of sutures enhances resistance to tensile force in general. However, there was no significant biomechanical difference between the 6-sutured group in which the most sutures were used and the 4-sutured group. In functional examinations, overall successful results were obtained in the group with 4 sutures. In histological examinations, there was no statistical difference between the control group, 2-sutured groups, and 4-sutured groups in terms of connective tissue index. However, it was observed that the group with 6 sutures had a higher connective tissue index than the control group and groups with 2 and 4 sutures. In terms of regeneration index, it was found that repair with 4 sutures was superior to repair with 2 and 6 sutures. No difference was found between any of the suture groups according to the diameter change index., Conclusions: These results indicate that repair with 4 sutures is the best method of epineural repair that provides both strength and regeneration. These findings will contribute to both the repair of clinically similar nerves and the standardization of rat nerve studies., Competing Interests: Conflicts of interest and sources of funding: none declared., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Peripheral nerve injuries are common and serious conditions. The effect of Neurotropin® (NTP), a nonprotein extract derived from the inflamed skin of rabbits inoculated with vaccinia virus, on peripheral nerve regeneration has not been fully elucidated. However, it has analgesic properties via the activation of descending pain inhibitory systems. Therefore, the current study aimed to determine the effects of NTP on peripheral nerve regeneration., Methods: We examined axonal outgrowth of dorsal root ganglion (DRG) neurons using immunocytochemistry in vitro. In addition, nerve regeneration was evaluated functionally, electrophysiologically, and histologically in a rat sciatic nerve crush injury model in vivo. Furthermore, gene expression of neurotrophic factors in the injured sciatic nerves and DRGs was evaluated., Results: In the dorsal root ganglion neurons in vitro, NTP promoted axonal outgrowth at a concentration of 10 mNU/mL. Moreover, the systemic administration of NTP contributed to the recovery of motor and sensory function at 2 weeks, and of sensory function, nerve conduction velocity, terminal latency, and axon-remyelination 4 weeks after sciatic nerve injury. In the gene expression assessment, insulin-like growth factor 1 and vascular endothelial growth factor expressions were increased in the injured sciatic nerve 2 days postoperatively., Conclusions: Therefore, NTP might be effective in not only treating chronic pain but also promoting peripheral nerve regeneration after injury., Competing Interests: Declaration of competing interest The funding sponsor, Nippon Zoki Pharmaceutical Co., Ltd., had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, and in the decision to publish the results. The authors have declared that no further conflict of interest exists., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Background:  Photochemical tissue bonding (PTB) is a technique for peripheral nerve repair in which a collagenous membrane is bonded around approximated nerve ends. Studies using PTB with cryopreserved human amnion have shown promising results in a rat sciatic nerve transection model including a more rapid and complete return of function, larger axon size, and thicker myelination than suture repair. Commercial collagen membranes, such as dehydrated amnion allograft, are readily available, offer ease of storage, and have no risk of disease transmission or tissue rejection. However, the biomechanical properties of these membranes using PTB are currently unknown in comparison to PTB of cryopreserved human amnion and suture neurorrhaphy., Methods:  Rat sciatic nerves ( n  = 10 per group) were transected and repaired using either suture neurorrhaphy or PTB with one of the following membranes: cryopreserved human amnion, monolayer human amnion allograft (crosslinked and noncrosslinked), trilayer human amnion/chorion allograft (crosslinked and noncrosslinked), or swine submucosa. Repaired nerves were subjected to mechanical testing., Results:  During ultimate stress testing, the repair groups that withstood the greatest strain increases were suture neurorrhaphy (69 ± 14%), PTB with crosslinked trilayer amnion (52 ± 10%), and PTB with cryopreserved human amnion (46 ± 20%), although the differences between these groups were not statistically significant. Neurorrhaphy repairs had a maximum load (0.98 ± 0.30 N) significantly greater than all other repair groups except for noncrosslinked trilayer amnion (0.51 ± 0.27 N). During fatigue testing, all samples repaired with suture, or PTBs with either crosslinked or noncrosslinked trilayer amnion were able to withstand strain increases of at least 50%., Conclusion:  PTB repairs with commercial noncrosslinked amnion allograft membranes can withstand physiological strain and have comparable performance to repairs with human amnion, which has demonstrated efficacy in vivo. These results indicate the need for further testing of these membranes using in vivo animal model repairs., Competing Interests: None declared., (Thieme. All rights reserved.)

Case: A 31-year-old patient presented with an encapsulated sciatic nerve secondary to extensive hip heterotopic ossification (HO), which prevented visualization of a safe osteotomy site to avoid nerve damage. The 3D-printed model demonstrated an easily identifiable osseous reference point along the inferior aspect of the heterotopic mass, allowing for a vertical osteotomy to be safely performed., Conclusion: HO is associated with loss of normal anatomic topography. The current case report illustrates the use of a 3D-printed model to identify pertinent anatomic landmarks required for safe decompression of an encapsulated sciatic nerve within the anatomic region of the hip., Competing Interests: Disclosure: The Disclosure of Potential Conflicts of Interest forms are provided with the online version of the article (http://links.lww.com/JBJSCC/C298)., (Copyright © 2024 by The Journal of Bone and Joint Surgery, Incorporated.)

Objectives: To assess the supraspinal working mechanisms of the burst spinal cord stimulation (SCS) mode, we used functional magnetic resonance imaging (fMRI) in chronic neuropathic rats. We hypothesized that active recharge burst SCS would induce a more profound blood oxygenation level–dependent (BOLD) signal increase in areas associated with cognitive‐emotional aspects of pain, as compared to tonic SCS. Methods: Sprague Dawley rats (n = 17) underwent a unilateral partial sciatic nerve ligation, which resulted in chronic neuropathic pain. Quadripolar SCS electrodes were epidurally positioned on top of the dorsal columns at Th13. Isoflurane‐anesthetized (1.5%) rats received either tonic SCS (n = 8) or burst SCS (n = 9) at 66% of motor threshold. BOLD fMRI was conducted before, during, and after SCS using a 9.4‐T horizontal bore scanner. Results: Overall, both tonic and burst SCS induced a significant increase of BOLD signal levels in areas associated with the location and intensity of pain, and areas associated with cognitive‐emotional aspects of pain. Additionally, burst SCS significantly increased BOLD signal levels in the raphe nuclei, nucleus accumbens, and caudate putamen. Tonic SCS did not induce a significant increase in BOLD signal levels in these areas. Conclusions: In conclusion, active recharge burst and tonic SCS have different effects on the intensity and localization of SCS‐induced activation responses in the brain. This work demonstrates that active recharge burst is another waveform that can engage brain areas associated with cognitive‐emotional aspects of pain as well as areas associated with location and intensity of pain. Previous studies showing similar engagement used only passive recharge burst. [ABSTRACT FROM AUTHOR]

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Background: The basic perineural catheter design has changed minimally since inception, with the catheter introduced through or over a straight needle. The U.S. Food and Drug Administration recently cleared a novel perineural catheter design comprising a catheter attached to the back of a suture-shaped needle that is inserted, advanced along the arc of its curvature pulling the catheter past the target nerve, and then exited through the skin in a second location. The authors hypothesized that analgesia would be noninferior using the new versus traditional catheter design in the first two days after painful foot/ankle surgery with a primary outcome of average pain measured with the Numeric Rating Scale.Methods: Subjects undergoing painful foot or ankle surgery with a continuous supraparaneural popliteal-sciatic nerve block 5 cm proximal to the bifurcation were randomized to either a suture-type or through-the-needle catheter and subsequent 3-day 0.2% ropivacaine infusion (basal 6 ml/h, bolus 4 ml, lockout 30 min). Subjects received daily follow-up for the first four days after surgery, including assessment for evidence of malfunction or dislodgement of the catheters.Results: During the first two postoperative days the mean ± SD average pain scores were lower in subjects with the suture-catheter (n = 35) compared with the through-the-needle (n = 35) group (2.7 ± 2.4 vs. 3.4 ± 2.4) and found to be statistically noninferior (95% CI, -1.9 to 0.6; P < 0.001). No suture-style catheter was completely dislodged (0%), whereas the tips of three (9%) traditional catheters were found outside of the skin before purposeful removal on postoperative day 3 (P = 0.239).Conclusions: Suture-type perineural catheters provided noninferior analgesia compared with traditional catheters for continuous popliteal-sciatic blocks after painful foot and ankle surgery. The new catheter design appears to be a viable alternative to traditional designs used for the past seven decades. [ABSTRACT FROM AUTHOR]

Background: For peripheral nerve defects, autografting is considered the therapeutic gold-standard treatment. However, this procedure leads to donor-site morbidity. While various artificial conduits have been recently developed, treatment outcome has been demonstrated to be poorer than that with autograft. In our previous study using a rat sciatic nerve crush injury model, we demonstrated that the delivery of electrospun nanofiber sheets incorporating methylcobalamin (MeCbl sheet) to the local site of a peripheral nerve injury promoted peripheral nerve regeneration. In this study, we examined the effects of combination therapy using an MeCbl sheet and a polyglycolic acid tube filled with collagen sponge (PGA-c) in a rat model of a 10-mm sciatic nerve defect.Methods: The rats were divided into 4 groups: (1) sham group (n = 10); (2) PGA-c group (n = 9), in which the gap was bridged using a PGA-c; (3) PGA-c/Sheet group (n = 8), in which the gap was bridged using a PGA-c wrapped in an MeCbl sheet; and (4) autograft group (n = 10), in which the gap was bridged using a reversed autograft. Motor and sensory function were evaluated, electrophysiological analysis was performed, and histomorphological findings were analyzed at 12 weeks postoperatively.Results: Compared with the PGA-c group, the PGA-c/Sheet group demonstrated significant improvements in the paw-withdrawal threshold expressed as a ratio relative to the contralateral side (mean difference [MD], -1.51; 95% confidence interval [CI], -2.64 to -0.38), terminal latency (MD, -0.86 ms; 95% CI, -1.56 to -0.16 ms), myelinated axon area (MD, 4.97%; 95% CI, 0.14% to 9.80%), proportion of myelinated axons (MD, 8.453%; 95% CI, 0.001% to 16.905%), and g-ratio (MD, -0.018; 95% CI, -0.035 to -0.001). No significant improvements were observed regarding motor function, electrophysiological findings with the exception of terminal latency, and axon numbers.Conclusions: An MeCbl sheet in combination with a PGA-c significantly accelerated recovery with respect to sensory function, electrophysiology, and histomorphometry.Clinical Relevance: An MeCbl sheet may represent an effective therapeutic strategy for promoting regeneration across a nerve gap bridged with an artificial conduit. [ABSTRACT FROM AUTHOR]

Background: Experimental and clinical studies have shown that tonic spinal cord stimulation (SCS) releases gamma‐aminobutyric acid (GABA) in the spinal dorsal horn. Recently, it was suggested that burst SCS does not act via spinal GABAergic mechanisms. Therefore, we studied spinal GABA release during burst and tonic SCS, both anatomically and pharmacologically, in a well‐established chronic neuropathic pain model. Methods: Animals underwent partial sciatic nerve ligation (PSNL). Quantitative immunohistochemical (IHC) analysis of intracellular GABA levels in the lumbar L4 to L6 dorsal spinal cord was performed after 60 minutes of burst, tonic, or sham SCS in rats that had undergone PSNL (n = 16). In a second pharmacological experiment, the effects of intrathecal administration of the GABAA antagonist bicuculline (5 μg) and the GABAB antagonist phaclofen (5 μg) were assessed. Paw withdrawal thresholds to von Frey filaments of rats that had undergone PSNL (n = 20) were tested during 60 minutes of burst and tonic SCS 30 minutes after intrathecal administration of the drugs. Results: Quantitative IHC analysis of GABA immunoreactivity in spinal dorsal horn sections of animals that had received burst SCS (n = 5) showed significantly lower intracellular GABA levels when compared to sham SCS sections (n = 4; P = 0.0201) and tonic SCS sections (n = 7; P = 0.0077). Intrathecal application of the GABAA antagonist bicuculline (5 μg; n = 10) or the GABAB antagonist phaclofen (5 μg; n = 10) resulted in ablation of the analgesic effect for both burst SCS and tonic SCS. Conclusions: In conclusion, our anatomical and pharmacological data demonstrate that, in this well‐established chronic neuropathic animal model, the analgesic effects of both burst SCS and tonic SCS are mediated via spinal GABAergic mechanisms. [ABSTRACT FROM AUTHOR]

Introduction: In this study we present a reproducible technique to assess motor recovery after nerve injury via neuromuscular junction (NMJ) immunostaining and electrodiagnostic testing.Methods: Wild-type mice underwent sciatic nerve transection with repair. Hindlimb muscles were collected for microscopy up to 30 weeks after injury. Immunostaining was used to assess axons (NF200), Schwann cells (S100), and motor endplates (α-bungarotoxin). Compound motor action potential (CMAP) amplitude was used to assess tibialis anterior (TA) function.Results: One week after injury, nearly all (98.0%) endplates were denervated. At 8 weeks, endplates were either partially (28.3%) or fully (71.7%) reinnervated. At 16 weeks, NMJ reinnervation reached 87.3%. CMAP amplitude was 83% of naive mice at 16 weeks and correlated with percentage of fully reinnervated NMJs. Morphological differences were noted between injured and noninjured NMJs.Discussion: We present a reproducible method for evaluating NMJ reinnervation. Electrodiagnostic data summarize NMJ recovery. Characterization of wild-type reinnervation provides important data for consideration in experimental design and interpretation. [ABSTRACT FROM AUTHOR]

Objective: This study aimed to introduce a reliable and useful model of selective sensorial or motor denervations of the sciatic nerve in rats with clinical and laboratory outcomes., Methods: The surgical technique was determined via detailed cadaveric dissections of rat sciatic nerve roots and cross-sectional histoanatomy. Forty animals were divided into the sham, sensorial denervation (SD), motor denervation (MD), and combined denervation (CD) groups and evaluated clinically via the pinch test and observation. Electrophysiological tests, retrograde neuronal labeling, and histologic and radiographic studies were performed. The weights of the muscles innervated by the sciatic nerve were measured., Results: The nerve root topography at the L4 level was consistent. Hemilaminectomy satisfactorily exposed all the roots contributing to the sciatic nerve and selectively denervated its sensorial and motor zones. Sensorial denervation caused foot deformities and wound problems, which were more severe in SD than in MD and CD. Nerve histomorphometry, electrophysiological tests, retrograde neuronal labeling studies, and measurements of the muscle weights also verified the denervations., Conclusion: This study has shown the feasibility of selective (sensory or motor) sciatic nerve denervation through a single-level hemilaminectomy. The surgical technique is reliable and has a confounding effect on gait. Sensorial denervation had more severe foot problems than motor and combined denervation in rats.

Objective: Acute limb ischemia (ALI) is a rapid decrease in lower limb blood flow due to acute occlusion of peripheral arteries or bypass grafts. This study aimed to establish an ALI model using microsized gelatin beads and to investigate the pathophysiological conditions., Methods: Male Sprague-Dawley rats were anesthetized, and a low or high dose of microsized gelatin beads was administered into the left femoral artery on days 0 and 7. A control, that is, normal saline (NS) group in which NS was administered in the left femoral artery, a femoral artery cut (FAC) group in which the left femoral artery was cut, and a sciatic nerve cut (SNC) group in which the left sciatic nerve was cut were prepared. After 21 days, the temperature changes and the muscle weights in the lower limbs were measured. To assess nerve damage, the L1-6 sympathetic ganglia were immunostained with activating transcription factor 3 (ATF3) antibody., Results: In the Low-dose, High-dose, and FAC groups, a decrease in temperature was predominantly observed in the left limb. In the High-dose and SNC groups, the weight of the soleus muscle and extensor digitorum longus in the left limb decreased; however, no weight changes were observed in the Low-dose and FAC groups. Conversely, the weight of the gastrocnemius muscle significantly decreased in the Low-dose, High-dose, FAC, and SNC groups. In the High-dose and SNC groups, the number of ATF3-positive cells in the sympathetic ganglia significantly increased, and in the Low-dose, a small number of ATF3-positive cells were observed. However, ATF3-positive cells were rarely observed in the FAC and NS groups., Conclusion: We established an ALI rat model using microsized gelatin beads. The results of this study suggest that autonomic neuropathy in ALI is related to both muscle damage and peripheral neuropathy., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Purpose: To repair peripheral nerve defects and seek alternatives for autografts, nerve conduits with various growth factors and cells have been invented. Few pieces of literature report the effect of nerve conduits plus platelet-rich fibrin (PRF). This study aimed to investigate the effectiveness of nerve conduits filled with PRF., Methods: The model of a 10 mm sciatic nerve gap in a rat was used to evaluate peripheral nerve regeneration. The thirty rats were randomly divided into one of the following three groups (n = 10 per group). Autogenous nerve grafts (autograft group), conduits filled with phosphate-buffered saline (PBS) (PBS group), or conduits filled with PRF group (PRF group). We assessed motor and sensory functions for the three groups at 4, 8, and 12 weeks postoperatively. In addition, axon numbers were measured 12 weeks after repair of the peripheral nerve gaps., Results: Significant differences in motor function were observed between the autograft group and the other two groups at 12 weeks postoperatively. In the test to evaluate the recovery of sensory function, there were significant differences between the PBS group and the other two groups at all time points. The most axon number was found in the autograft group. The axon number of the PRF group was significantly more extensive than that of the PBS group., Conclusions: The nerve conduit filled with PRF promoted the axon regeneration of the sciatic nerve and improved sensory function., Competing Interests: Declaration of Competing Interest The authors declare that there is no conflict of interest., (Copyright © 2023 Elsevier B.V. All rights reserved.)

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., (© 2024 Wiley Periodicals LLC.)

Background: Human umbilical cord (hUC) is encompassed by a mucoid connective tissue called Wharton's jelly (WJ), made of hyaluronic acid, collagen, and stromal cells to support the blood vessels of hUC. This study was aimed to determine the in vitro neuronal differentiation of WJ-derived mesenchymal stem cells (WJMSCs), and in vivo axonal regeneration potential of nanofiber coated human Wharton's jelly as a neuronal graft after sciatic nerve injury in immunosuppressed albino Wistar rats., Materials and Methods: Wharton's jelly-derived mesenchymal stem cells could be differentiated to neuron-like cells by inducing with neuronic supplementing media. The test animal's axotomized nerves were implanted with trimmed human umbilical cord devoid of vascularity and nanocoated with electro-spun poly-l-lactic acid nanofibers. The control animals were bridged with native sciatic nerve reversed and sutured. Post-surgical functional recovery was studied by walking track, pinprick, muscle weight, and sweating quantification. At the end of the 4th week, the animals were euthanized, and magnetoneurography was performed. The explanted grafts were quantified by immunohistochemistry for immuno-rejection, neural scarring, neural adhesion axon regeneration, fibre diameter, myelin thickness, and G-ratio. The sciatic function index values were similar by walking track analysis for both the test and control groups., Results: The animals had functional and sensation recovery by the end of 2 weeks. No mortality, signs of inflammation, and acute immune rejection were observed post-surgery., Conclusions: The hUCWJ devoid of vascular elements can be a perfect peripheral nerve graft, and we hypothesis that the cryopreserved hUC could be an ideal resource for axonal regeneration in the future.

Background: Motor function recovery following acellular nerve allograft (ANA) repair remains inferior to autologous nerve reconstruction. We investigated the functional recovery of ANAs after combined mesenchymal stem cell (MSC) delivery and surgical angiogenesis in a rat sciatic nerve defect model., Methods: In 100 Lewis rats, unilateral sciatic nerve defects were reconstructed with (I) autografts, (II) ANAs, (III) ANAs wrapped with a superficial inferior epigastric artery fascial (SIEF) flap, combined with either (IV) undifferentiated MSCs or (V) Schwann cell-like differentiated MSCs. The tibialis anterior muscle area was evaluated during the survival period using ultrasonography. Functional recovery, histomorphometry, and immunofluorescence were assessed at 12 and 16 weeks., Results: At 12 weeks, the addition of surgical angiogenesis and MSCs improved ankle contractures. The SIEF flap also significantly improved compound muscle action potential (CMAP) outcomes compared with ANAs. Autografts outperformed all groups in muscle force and weight. At 16 weeks, ankle contractures of ANAs remained inferior to autografts and SIEF, whereas the CMAP amplitude was comparable between groups. The muscle force of autografts remained superior to all other groups, and the muscle weight of ANAs remained inferior to autografts. No differences were found in histomorphometry outcomes between SIEF groups and ANAs. Vascularity, determined by CD34 staining, was significantly higher in SIEF groups compared with ANAs., Conclusions: The combination of surgical angiogenesis and MSCs did not result in a synergistic improvement in functional outcomes. In a short nerve gap model, the adipofascial flap may provide sufficient MSCs to ANAs without additional ex vivo MSC seeding., Competing Interests: Declaration of Competing Interest None declared., (Copyright © 2023 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved.)

Purpose: Polyethylene glycol is known to improve recovery following its use in repair of acute peripheral nerve injury. The duration till which PEG works remains a subject of intense research. We studied the effect of PEG with augmentation of 20Htz of electrical stimulation (ES) following neurorrhaphy at 48 h in a rodent sciatic nerve neurotmesis model., Method: Twenty-four Sprague Dawley rats were divided into 4 groups. In group I, the sciatic nerve was transected and repaired immediately. In group II, PEG fusion was done additionally after acute repair. In group III, repair and PEG fusion were done at 48 h. In group IV, ES of 20Htz at 2 mA for 1 h was added to the steps followed for group III. Weekly assessment of sciatic functional index (SFI), pinprick, and cold allodynia tests were done at 3 weeks and euthanized. Sciatic nerve axonal count and muscle weight were done., Results: Groups II, III, and IV showed significantly better recovery of SFI (II: 70.10 ± 1.24/III: 84.00 ± 2.59/IV: 74.40 ± 1.71 vs I: 90.00 ± 1.38) (p < 0.001) and axonal counts (II: 4040 ± 270/III: 2121 ± 450/IV:2380 ± 158 vs I: 1024 ± 094) (p < 0.001) at 3 weeks. The experimental groups showed earlier recovery of sensation in comparison to the controls as demonstrated by pinprick and cold allodynia tests and improved muscle weights. Addition of electrical stimulation helped in better score with SFI (III: 84.00 ± 2.59 vs IV: 74.40 ± 1.71) (p < 0.001) and muscle weight (plantar flexors) (III: 0.49 ± 0.02 vs IV: 0.55 ± 0.01) (p < 0.001) in delayed repair and PEG fusions., Conclusion: This study shows that PEG fusion of peripheral nerve repair in augmentation with ES results in better outcomes, and this benefit can be demonstrated up to a window period of 48 h after injury., (© 2023. The Author(s).)

The morphological structure reconstruction and functional recovery of long-distance peripheral nerve injury (PNI) are global medical challenges. Biodegradable nerve scaffolds that provide mechanical support for the growth and extension of neurites are a desired way to repair long-distance PNI. However, the synchrony of scaffold degradation and nerve regeneration is still challenging. Here, a novel bioinspired multichannel nerve guide conduit (MNGC) with topographical cues based on silk fibroin and ε-polylysine modification was constructed. This conduit (SF(A) + PLL MNGC) exhibited sufficient mechanical strength, excellent degradability, and favorable promotion of cell growth. Peripheral nerve repairing was evaluated by an in vivo 10 mm rat sciatic model. In vivo evidence demonstrated that SF(A) + PLL MNGC was completely biodegraded in the body within 4 weeks after providing sufficient physical support and guide for neurite extension, and a 10 mm sciatic nerve defect was effectively repaired without scar formation, indicating a high synchronous effect of scaffold biodegradation and nerve regeneration. More importantly, the regenerated nerve of the SF(A) + PLL MNGC group showed comparable morphological reconstruction and functional recovery to that of autologous nerve transplantation. This work proved that the designed SF(A) + PLL MNGC has potential for application in long-distance PNI repair in the clinic.