Nerve Compression Injury Research Articles

Temporal and spatial expression of Phosphodiesterase-4B after sciatic nerve compression in rats and its mechanism of action on sciatic nerve repair.

Macrophage phenotype transformation is vital in sciatic nerve injury. The study of biomolecule expression and its impact on macrophage phenotype transformation is a current research focus. We created a rat model of sciatic nerve compression injury to examine the expression of PDE4B and the distribution of M1 and M2 macrophages over time and their relationship. We confirmed the effect of inhibiting PDE4B expression on macrophage phenotype changes and its role in sciatic nerve injury repair. The experiments consisted of immunofluorescence, western blotting, HE staining, TEM, and behavioral evaluation. Investigate in vivo experiment results with RAW264.7 cells in vitro. PDE4B knockdown lentivirus was transfected into RAW264.7 cells and stimulated with LPS and IFN-γ. We assessed CD86 and CD206 expression using flow cytometry and western blot. The relationship between PDE4B and the TLR4/NF-κB pathway was studied. PDE4B peaked on day 7 after surgery, alongside the highest M1 macrophages count. PDE4B and M1 macrophages decreased, and M2 macrophages increased. PDE4B inhibition reduced M1 macrophages, increased M2 macrophages, suppressed inflammation, and promoted sciatic nerve repair while alleviating pain. In vitro experiments confirmed that PDE4B regulated macrophage phenotype via the TLR4/NF-κB pathway. Inhibiting PDE4B disrupted this pathway and promoted M2 macrophage transformation. In the sciatic nerve injury, PDE4B expression is linked to the M1 macrophage phenotype. Low PDE4B expression facilitates the M1 to M2 macrophage transformation and supports sciatic nerve repair. The TLR4/NF-κB pathway is involved in this process.

Analgesic effect of Dahuang Fuzi Decoction in neuropathic pain through inhibiting TNF-α and PI3K-AKT signaling.

Neuropathic pain (NeP) presents considerable challenges in terms of effective management and significantly impacts the quality of life for affected patients. The current treatment options for NeP are limited, highlighting the need for alternative therapeutic approaches. Dahuang Fuzi Decoction (DF), a formula from traditional Chinese medicine, has shown potential in relieving pain symptoms associated with various types of NeP. However, the mechanisms through which DF exerts its effects remain largely unknown. In this study, we employed ultra-high-performance liquid chromatography coupled with high-resolution mass spectrometry (UHPLC-HRMS) to analyze the chemical composition of DF. A chronic sciatic nerve compression injury (CCI) rat mode was used to assess the analgesic efficacy of DF for NeP. Network pharmacology analysis was performed to identify the potential signaling pathways affected by DF. DF treatment significantly increased the mechanical withdrawal threshold (MWT) and thermal withdrawal latency (TWL) in CCI rats, indicating its analgesic effect. Network pharmacology analysis suggested that DF potentially modulated TNF-α and PI3K-AKT signaling pathways. Furthermore, DF treatment decreased the levels of pro-inflammatory cytokines (IL-1β, IL-6, and TNF-α) in spinal cord tissues of CCI rats, suggesting an anti-inflammatory effect. Western blot analysis revealed that DF treatment reduced the expression of TNF-α, TNFR1, and phosphorylated forms of PI3K, AKT, IKKα/β, IKBα, and NF-κB in the spinal cord of CCI rats. Immunofluorescence analysis confirmed significant reductions in TNF-α and TNFR1 expression, as well as in AKT and NF-κB phosphorylation within astrocytes following DF administration. Our findings characterize the chemical constituents of DF and elucidate its underlying mechanism for relieving NeP. The analgesic effect of DF involves the inhibition of TNF-α and PI3K-AKT signaling pathways, providing a potential therapeutic approach for NeP management.

Early and Late Intrinsic Hand Muscle Reinnervation After End-to-Side AIN to Ulnar Motor Nerve Transfer.

The "supercharge" end-to-side (SETS) anterior-interosseous-nerve (AIN) to ulnar-motor nerve transfer is used to improve intrinsic muscle recovery in cases of severe ulnar nerve compression or proximal axonotmetic injuries. Previous work has found differing intrinsic muscle recovery after this transfer. The objectives of this study were to examine the patterns of recovery in first dorsal interossei (FDI) and abductor digiti minimi (ADM) and the impact of AIN transfer to a specific fascicular location on the ulnar-motor nerve. A retrospective review of one fellowship-trained surgeon's consecutive patients at a single center from December 2019 to September 2021 was conducted. Patients who had an AIN to ulnar-motor nerve transfer for any indication were included and were excluded if they had less than 9 months follow-up. Seventeen patients were included (88% male, mean age 55 ± 14 years). At early follow-up, compound muscle action potential amplitudes for ADM and FDI did not increase. Compound muscle action potential amplitude for ADM significantly increased at late follow-up (P < .01). Average British Medical Research Council (BMRC) strength increased at early follow-up for FDI (P < .05), but not ADM. The proportion of patients with BMRC ≥ 3 increased for FDI (P < .01) and ADM (P < .05) at late follow-up. Volar-ulnar AIN insertion position did not have a clear effect on outcomes. The SETS AIN to ulnar-motor nerve transfer demonstrates clinical and electrophysiologic evidence of intrinsic muscle recovery and reinnervation, with differing recovery of outcomes. The role of specific fascicular targeting is still unclear and required further examination as does the mechanism behind differing intrinsic recovering.

Exogenous NT-3 Promotes Phenotype Switch of Resident Macrophages and Improves Sciatic Nerve Injury through AMPK/NF-κB Signaling Pathway.

Neurotrophin-3 (NT-3) is an important family of neurotrophic factors with extensive neurotrophic activity, which can maintain the survival and regeneration of nerve cells. However, the mechanism of NT-3 on macrophage phenotype transformation after sciatic nerve injury is not clear. In this study, we constructed a scientific nerve compression injury animal model and administered different doses of NT-3 treatment through osmotic minipump. 7 days after surgery, we collected sciatic nerve tissue and observed the distribution of macrophage phenotype through iNOS and CD206 immunofluorescence. During the experiment, regular postoperative observations were conducted on rats. After the experiment, sciatic nerve tissue was collected for HE staining, myelin staining, immunofluorescence staining, and Western blot analysis. To verify the role of the AMPK/NF-κB pathway, we applied the AMPK inhibitor Compound C and the NF-κB inhibitor BAY11-7082 to repeat the above experiment. Our experimental results reveal that NT-3 promotes sciatic nerve injury repair and polarization of M2 macrophage phenotype, promotes AMPK activation, and inhibits NF-κB activation. The repair effect of high concentration NT-3 on sciatic nerve injury is significantly enhanced compared to low concentration. Compound C administration can weaken the effect of NT-3, while BAY 11-7082 can enhance the effect of NT-3. In short, NT-3 significantly improves sciatic nerve injury in rats, promotes sciatic nerve function repair, accelerates M2 macrophage phenotype polarization, and improves neuroinflammatory response. The protective effects of NT-3 mentioned above are partially related to the AMPK/NF-κB signal axis.

Exploring the Therapeutic Potential of Mesenchymal Stem Cells-derived conditioned medium: An In-depth Analysis of Pain Alleviation, Spinal CCL2 Levels, and Oxidative Stress.

Neuropathic pain, a debilitating condition, remains a significant challenge due to the lack of effective therapeutic solutions. This study aimed to evaluate the potential of mesenchymal stromal cell (MSC)-derived conditioned medium in alleviating neuropathic pain induced by sciatic nerve compression injury in adult male rats. Forty Wistar rats were randomly assigned to four groups: control, nerve injury, nerve injury with intra-neural injection of conditioned medium, and nerve injury with intra-neural injection of culture medium. Following sciatic nerve compression, the respective groups received either 10 µl of conditioned medium from amniotic fluid-derived stem cells or an equal volume of control culture medium. Behavioral tests for cold allodynia, mechanical allodynia, and thermal hyperalgesia were conducted, and the spinal cord was analyzed using Western Blot and oxidative stress assays. The behavioral experiments showed a decrease in mechanical hyperalgesia and cold allodynia in the group receiving conditioned medium compared to the injury group and the control medium group. Western blot data revealed a decrease in the expression of the CCL2 protein and an increase in GAD65. Oxidative stress tests also showed increased levels of SOD and glutathione in conditioned media-treated animals compared to animals with nerve injury. The findings suggest that conditioned medium derived from amniotic fluid-derived stem cells can effectively reduce neuropathic pain, potentially through the provision of supportive factors that mitigate oxidative stress and inflammation in the spinal cord.

Myelinated peripheral axons are more vulnerable to mechanical trauma in a model of enlarged axonal diameters.

The velocity of axonal impulse propagation is facilitated by myelination and axonal diameters. Both parameters are frequently impaired in peripheral nerve disorders, but it is not known if the diameters of myelinated axons affect the liability to injury or the efficiency of functional recovery. Mice lacking the adaxonal myelin protein chemokine-like factor-like MARVEL-transmembrane domain-containing family member-6 (CMTM6) specifically from Schwann cells (SCs) display appropriate myelination but increased diameters of peripheral axons. Here we subjected Cmtm6-cKo mice as a model of enlarged axonal diameters to a mild sciatic nerve compression injury that causes temporarily reduced axonal diameters but otherwise comparatively moderate pathology of the axon/myelin-unit. Notably, both of these pathological features were worsened in Cmtm6-cKo compared to genotype-control mice early post-injury. The increase of axonal diameters caused by CMTM6-deficiency thus does not override their injury-dependent decrease. Accordingly, we did not detect signs of improved regeneration or functional recovery after nerve compression in Cmtm6-cKo mice; depleting CMTM6 in SCs is thus not a promising strategy toward enhanced recovery after nerve injury. Conversely, the exacerbated axonal damage in Cmtm6-cKo nerves early post-injury coincided with both enhanced immune response including foamy macrophages and SCs and transiently reduced grip strength. Our observations support the concept that larger peripheral axons are particularly susceptible toward mechanical trauma.

Stigmasterol alleviates neuropathic pain by reducing Schwann cell-macrophage cascade in DRG by modulating IL-34/CSF1R.

This study aimed to investigate the potential therapeutic applications of stigmasterol for treating neuropathic pain. Related mechanisms were investigated by DRG single-cell sequencing analysis and the use of specific inhibitors in cellular experiments. In animal experiments, 32 male Sprague-Dawley rats were randomly divided into the sham operation group, CCI group, ibuprofen group, and stigmasterol group. We performed behavioral tests, ELISA, H&E staining and immunohistochemistry, and western blotting. Cell communication analysis by single-cell sequencing reveals that after peripheral nerve injury, Schwann cells secrete IL-34 to act on CSF1R in macrophages. After peripheral nerve injury, the mRNA expression levels of CSF1R pathway and NLRP3 inflammasome in macrophages were increased in DRG. Invitro studies demonstrated that stigmasterol can reduce the secretion of IL-34 in LPS-induced RSC96 Schwann cells; stigmasterol treatment of LPS-induced Schwann cell-conditioned medium (L-S-CM) does not induce the proliferation and migration of RAW264.7 macrophages; L-S-CM reduces CSF1R signaling pathway (CSF1R, P38MAPK, and NFκB) activation, NLRP3 inflammasome activation, and ROS production. Invivo experiments have verified that stigmasterol can reduce thermal and cold hyperalgesia in rat chronic compressive nerve injury (CCI) model; stigmasterol can reduce IL-1β, IL-6, TNF-α, CCL2, SP, and PGE2 in serum of CCI rats; immunohistochemistry and western blot confirmed that stigmasterol can reduce the levels of IL-34/CSF1R signaling pathway and NLRP3 inflammasome in DRG of CCI rats. Stigmasterol alleviates neuropathic pain by reducing Schwann cell-macrophage cascade in DRG by modulating IL-34/CSF1R axis.

Use of the spider limb positioner for fibular free flap reconstruction of head and neck bony defects

Osseous and osteocutaneous fibular free flaps are the workhorse of maxillomandibular reconstruction over 30years after the initial description. Since 2019, we have routinely used the Spider Limb Positioner, adapted from its use in shoulder orthopedic procedures, for fibular free flap harvest. Herein, we describe this novel technique in our cohort. We describe our intraoperative setup and endorse the versatility and utility of this technique in comparison to other reported fibular free flap harvest techniques. The Spider Limb Positioner was used 61 times in 60 different patients to harvest osseous or osteocutaneous fibular free flaps. Median (range) tourniquet time for flap harvest was 90 (40-124) minutes. No iatrogenic nerve compression injuries or complications related to lower extremity positioning occurred. We describe a novel approach to fibular free flap harvest utilizing the Spider Limb Positioner, which affords optimal ergonomics, visibility, and patient repositioning. There were no nerve injuries or complications related to positioning in our series.

Optimal retractor insertion point for nerve safety during total hip arthroplasty: an anatomical study on the femoral and sciatic nerves in relation to hip motion.

Nerve injury is one of the most serious complications of total hip arthroplasty (THA). It is suspected to be a result from nerve compression or direct injury caused by an acetabular retractor. The anatomical relationship between the acetabular rim and the femoral and sciatic nerves, including hip motion, has not been investigated. This study aimed to identify the optimal position for retractor insertion during THA to prevent nerve damage. A total of 28 hip joints from 14 freshly frozen cadavers were used. Using an anterolateral approach, each cadaver was immobilised in the lateral decubitus position and deployed to measure the distance between the nerves and the acetabular rim, while the hip joint was changed to the extension, neutral, and flexion positions. Three femoral nerves were closest to the anterior margin of the acetabulum at 90° and 120° of extension and farthest away at 30° of flexion. The sciatic nerve was closest to the posterior margin of the acetabulum at 90° and 120° of flexion and farthest away at 30° and 150° of extension compared with the other points. To prevent nerve damage during THA, we suggest that the retractor be inserted at the points where the nerves are the farthest away, such as at 30° and 150°. The femoral and sciatic nerves vary in their movements depending on the hip position. Therefore, the safe insertion of a retractor is recommended for hip flexion of the femoral nerve and extension of the sciatic nerve. Additionally, it is important to carefully insert the retractor along the acetabular margin without penetrating the joint capsule. Overall, this study provides valuable insights into the anatomical location and movement of the femoral and sciatic nerves in relation to hip motion and can help inform surgical techniques for safer THA.

Chapter 9 - Fibular (peroneal) neuropathy

Fibular neuropathy has variable presenting features depending on the site of the lesion. Anatomical features make it susceptible to injury from extrinsic factors, particularly the superficial location of the nerve at the head of the fibula. There are many mechanisms of compression or other traumatic injury of the fibular nerve, as well as entrapment and intrinsic nerve lesions. Intraneural ganglion cysts are increasingly recognized when the mechanism of neuropathy is not clear from the medical history. Electrodiagnostic testing can contribute to the localization as well as the characterization of the pathologic process affecting the nerve. When the mechanism of injury is unclear from the analysis of the presentation, imaging with MRI and ultrasound may identify nerve lesions that warrant surgical intervention. The differential diagnosis of foot drop includes fibular neuropathy and other neurologic conditions, which can be distinguished through clinical and electrodiagnostic assessment. Rehabilitation measures, including ankle splinting, are important to improve function and safety when foot drop is present. Fibular neuropathy is less frequently painful than many other nerve lesions, but when it is painful, neuropathic medication may be required. Failure to spontaneously recover or the detection of a mass lesion may require surgical management.

A Systematic Review of the Role of Magnetic Resonance Imaging in the Diagnosis and Detection of Neurovascular Conflict in Patients With Trigeminal Neuralgia.

Trigeminal neuralgia (TN) is a debilitating disorder causing severe, episodic, unilateral stabbing facial pain disturbing enough to disrupt the activities of daily life. Classic TN is caused due to compression injury of the trigeminal nerve at the cistern segment caused by either an artery or a vein, referred to as neurovascular contact or conflict (NVC). Magnetic resonance imaging (MRI) has been the standard tool for the diagnosis of NVC. This study aimed to determine the incidence of NVC in TN, as identified by MRI, assess the various MRI grading patterns among patients with TN, and identify the vessels primarily involved in NVC. A systematic search of studies that used MRI for the diagnosis of TN in reference to NVC was conducted on DOAJ and PubMed/PubMed Central. Data were extracted and entered into a Microsoft Excel spreadsheet. The outcomes measured were the incidence of NVC as shown in MRI, vessels involved in NVC, and MRI grading patterns. We identified and selected 20 studies that fulfilled inclusion/exclusion criteria. In total, 1,436 patients were enrolled in all included studies. The type of MRI used was 1.5 T or 3 T MRI. The mean age of the patients varied from 49 to 63 years, with an equivalent male-to-female ratio. NVC was seen in 1,276 cases out of 1,436 cases (88.85%) of TN on the ipsilateral side, as shown by MRI. The vessels involved were arteries in 80-90% of the cases, followed by veins. Among the arteries, the superior cerebellar artery was the most common artery (80-90% of cases). The grades of NVC as assessed by MRI included grades I, II, and III with varied proportions in different studies. NVC is a common problem in TN, wherein there is compression at the nerve root entry zone, and it shows a strong predilection for the elderly population. MRI seems to be a novel imaging diagnostic investigation to identify NVC associated with TN. Moreover, NVC grading must be done with MRI so that it may help the surgeon in stratifying the patient's treatment.

Nerve Injury and Photobiomodulation, a Promising Opportunity: A Scoping Review on Laser Assisted Protocols for Lesions in the Oral Region

The currently available therapeutic options for restoring function and sensitivity in long-term nervous injuries pose challenges. Microsurgery interventions for direct nerve repair often lead to serious complications and limited success. Non-surgical methods, although somewhat effective, have limited benefits. These methods involve drug administration, such as with analgesics or corticosteroids. Photobiomodulation therapy (PBMT) has emerged as a promising approach based on clinical and laboratory studies. PBMT stimulates the migration and proliferation of neuronal fiber cellular aggregates, as reported in the literature. Experimental studies on animal models with peripheral nerve compression injuries have shown that PBMT can enhance the functionality of damaged nerves, preserving their activity and preventing scar tissue formation. The mechanism of action depends on the wavelength, which can positively or negatively affect photo acceptor resonances, influencing their conformation and activities. These findings suggest that photobiomodulation may accelerate and improve nerve regeneration. This review explores various methodologies used in photobiomodulation for regenerating nerve sensitivity after surgical trauma involving nerve structures, in the oral and peri-oral region. Research was conducted to evaluate which laser-assisted therapeutic protocols are used to improve the recovery of nervous sensitivity, using the JBI methodology for scoping reviews and following the PRISMA methodology.

Expression and Role of Toll-like Receptors in Facial Nerve Regeneration after Facial Nerve Injury.

Facial nerve palsy directly impacts the quality of life, with patients with facial nerve palsy showing increased rates of depression and limitations in social activities. Although facial nerve palsy is not life-threatening, it can devastate the emotional and social lives of affected individuals. Hence, improving the prognosis of patients with this condition is of vital importance. The prognosis of patients with facial nerve palsy is determined by the cause of the disease, the degree of damage, and the treatment provided. The facial nerve can be easily damaged by middle ear and temporal bone surgery, trauma or infection, and tumors of the peripheral facial nerve or tumors surrounding the nerve secondary to systemic disease. In addition, idiopathic, acquired immunodeficiency syndrome and autoimmune diseases may damage the facial nerve. The treatment used for facial paralysis depends on the cause. Treatment of facial nerve amputation injury varies depending on the degree of facial nerve damage, comorbidities, and duration of injury. Recently, interest has increased in Toll-like receptors (TLRs) related to innate immune responses, as these receptors are known to be related to nerve regeneration. In addition to innate immune cells, both neurons and glia of the central nervous system (CNS) and peripheral nervous system (PNS) express TLRs. A comprehensive literature review was conducted to assess the expression and role of TLRs in peripheral nerve injury and subsequent regeneration. Studies conducted on rats and mice have demonstrated the expression of TLR1-13. Among these, TLR2-5 and TLR7 have received the most research attention in relation to facial nerve degeneration and regeneration. TLR10, TLR11, and TLR13 increase during compression injury of the facial nerve, whereas during cutting injury, TLR1-5, TLR8, and TLR10-13 increase, indicating that these TLRs are involved in the degeneration and regeneration of the facial nerve following each type of injury. Inadequate TLR expression or absence of TLR responses can hinder regeneration after facial nerve damage. Animal studies suggest that TLRs play an important role in facial nerve degeneration and regeneration.

Lentinan alleviates sciatic nerve injury by promoting autophagy to remove myelin fragments.

Lentinan, a natural drug with wide-ranging pharmacological activities, can regulate autophagy-the process through which Schwann cells (SCs) eliminate myelin fragments after peripheral nerve injury (PNI). However, the effect of lentinan after PNI and the role of accelerated myelin debris removal via autophagy in this process are unclear. This study examined the effect of lentinan on rat sciatic nerve repair following crush injury and the underlying mechanisms. After the successful establishment of the sciatic nerve compression injury model, group-specific treatments were performed. The treatment group received 20 mg/kg lentinan via intraperitoneal injection, while the model group was treated with normal saline. The recovery in each group was then evaluated. Further, a rat SC line (RSC96) was cultured in medium with/without lentinan after supplementation with homogenous myelin fractions to evaluate the removal of myelin particles. Our results showed that lentinan promotes autophagic flux in vivo via the AMPK/mTOR signaling pathway, accelerates the clearance of myelin debris by SCs, and inhibits neuronal apoptosis, thereby promoting neurological recovery. Similarly, in vitro experiments showed that lentinan promotes the phagocytosis of myelin debris by SCs. In conclusion, our results suggest that lentinan primarily promotes nerve regeneration by accelerating the autophagic clearance of myelin debris in SCs, and this process is likely regulated by the AMPK/mTOR signaling pathway. Therefore, this study provides compelling evidence that lentinan may be a cost-effective and natural treatment agent for PNI.

Long Non-Coding RNA-X-Inactive Specific Transcript Promotes the Retinal Ganglion Cell Survival After Optic Nerve Crush Injury by Upregulating miR-36

Retinal ganglion cells (RGC) axons participate in the construction of optic nerve, and prevent the damage of RGC during acute optic nerve injury. IncRNA-XIST is crucial for RGC apoptosis. Our study intends to assess IncRNA-XIST’s role in the regulation of RGC apoptosis in an attempt to provide a theoretical basis for treating optic nerve crush injury. Two genotypes of mice (wild-type and miR-36 KO) were used to establish an optic nerve crush injury model to investigate the regulatory role of IncRNA-XIST gene in RGCs apoptosis. These mice were then randomly assigned into control group (WT), injury group, and XIST/injury group. The changes of apoptotic genes and proteins in retinal ganglion cells were analyzed by qPCR, WB and TUNEL staining. In wild-type mice, RGC apoptosis was significantly increased after optic nerve compression injury, and the expression of Bax and Bad was significantly increased. When the LncRNA-XIST gene was overexpressed before retinal crush injury, the apoptosis of retinal ganglion cells was significantly reduced, and Bax and Bad levels were decreased as compared with model group of optic nerve injury. The results showed that in wild-type mice, overexpression of IncRNA-XIST gene promoted the survival of RGC after optic nerve crush injury. In addition, upregulation of IncRNA-xist expression in miR-36 KO mice did not reduce retinal ganglion cell apoptosis and alter the apoptotic protein expression after optic nerve crush injury. Defects of miR-36 alone or overexpression of XIST gene do not cause morphological damage of retina in mice. In mouse ganglion cells, miR-36 expression was up-regulated in both injured cells and overexpressed XIST gene. However, up-regulation of miR-36 caused by overexpression of XIST gene was more obvious. In addition, in vivo studies of wild-type mice, it was found that overexpression of XIST reduced retinal ganglion cell apoptosis, and this effect was abolished in miR-36 KO mice. In conclusion, lncRNA-XIST reduces ganglion cell apoptosis by upregulating miR-36 and promotes the survival of RGC after nerve crush injury.

Neurological Complications of Thread Lifting

State-of-art invasive cosmetic procedures in some cases can lead to the development of neurological complications, in particular neuropathy. Neuropathy can be manifested by sensory (pain), motor and autonomic disorders. Neurological complications of thread liftingare associated with injury to both sensoryand motor nerves;facial and trigeminal nerves are most commonly affected. In case of direct nerve injury with a needle, cannula or thread, acute neuropathy occurs. Compression nerve injury is associated with a delayed symptoms development. Clinical signs of sensory nerve injury may include paresthesia, dysesthesia, anesthesia, and neuropraxia. Nerve endings completely restore within up to 6 months, but in some cases, the injury can be catastrophic. The article presentsthe authors’ personal clinical observations.

Effects of apocynin on sciatic nerve injury in rabbits

ABSTRACT We investigated the effects of apocynin (APO) on experimental sciatic nerve compression injury in rabbits. We used 21 male rabbits divided randomly into three groups of seven. The control group was subjected to sciatic nerve compression with no further intervention. The APO treated group was subjected to compression injury and 20 mg/kg APO was administered daily for 21 days by intraperitoneal injection beginning the day after the injury. The sham group was treated with APO without injury. The control group exhibited shrinkage of axons, disruption of myelin sheaths and loss of nerve fibers. The damage for the control group was significantly greater than for the sham group. The severity of histopathology was decreased in the APO treated group compared to the control group, as was the oxidative stress index. Our findings suggest that APO treatment may contribute to healing of sciatic nerve damage.

Frankincense-Myrrh treatment alleviates neuropathic pain via the inhibition of neuroglia activation mediated by the TLR4/MyD88 pathway and TRPV1 signaling

Neuroglia are important modulators of neuronal functionality, and thus play an integral role in the pathogenesis and treatment of neuropathic pain (NP). According to traditional Chinese medicine, Frankincense-Myrrh is capable of "activating blood and dissipating blood stasis", and as such these two biological compounds are commonly used to treat NP, however, the mechanisms underlying the efficacy of such treatment are unclear. This study aimed to further elucidate the protective effects associated with the Frankincense-Myrrh treatment of NP. A chronic sciatic nerve compression injury (CCI) model of NP was established, after which animals were gavaged with Frankincense, Myrrh, Frankincense-Myrrh, or the positive control drug pregabalin for 14 days. Network pharmacology approaches were used to identify putative pathways and targets associated with the Frankincense-Myrrh-mediated treatment of NP, after which these targets were subjected to in-depth analyses. The impact of TLR4 blockade on NP pathogenesis was assessed by intrathecally administering a TLR4 antagonist (LRU) or the MyD88 homodimerization inhibitory peptide (MIP). Significant alleviation of thermal and mechanical hypersensitivity in response to Frankincense and Myrrh treatment was observed in NP model mice, while network pharmacology analyses suggested that the pathogenesis of NP may be related to TLR4/MyD88-mediated neuroinflammation. Consistently, Frankincense-Myrrh treatment was found to reduce TLR4, MyD88, and p-p65 expression in spinal dorsal horn neuroglia from treated animals, in addition to inhibiting neuronal TRPV1 and inflammatory factor expression. Intrathecal LRU and MIP delivery were sufficient to alleviate thermal and mechanical hyperalgesia in these CCI model mice, with concomitant reductions in neuronal TRPV1 expression and neuroglial activation in the spinal dorsal horn. These data suggest that Frankincense-Myrrh treatment was sufficient to alleviate NP in part via inhibiting TLR4/MyD88 pathway and TRPV1 signaling activity. Blocking TLR4 and MyD88 activation may thus hold value as a means of treating NP.

CT of Sacral Fractures: Classification Systems and Management.

CT is often performed as part of a whole-body protocol in the setting of polytrauma and is the standard of care for diagnosing and characterizing sacral fractures. These fractures are not uncommon, occurring in conjunction with pelvic ring disruption in approximately 40%-50% of patients. Knowledge of basic functional anatomy and fracture biomechanics is important in understanding sacral fracture patterns, which only rarely result from direct impact. More often, sacral fractures result from an indirect mechanism with fracture lines that propagate along relative lines of weakness, leading to predictable fracture patterns. Each fracture pattern has implications with respect to neurologic injury, spinopelvic stability, management, and potential complications. The authors explore the Denis, Roy-Camille, Isler, Robles, Sabiston-Wing, and shape-based classification systems for sacral fractures. These form the basis of the subsequently discussed unified AOSpine sacral fracture classification, a consensus system developed by spine and orthopedic surgeons as a means of improving and standardizing communication. The AOSpine sacral fracture classification also includes clinical designations for neurologic status and patient-specific modifiers. When a patient is unexaminable owing to obtundation or sedation, CT is an invaluable indirect marker of nerve compression or traction injury. It also plays an important role in visualizing and characterizing the type and extent of any associated soft-tissue injuries that may warrant a delay in surgery or an alternative operative approach. ©RSNA, 2022.

Involvement of GABAA-rho Receptor in a Trigeminal Neuralgia Model

The antiepileptic drug carbamazepine is effective in a subpopulation of trigeminal neuralgia patients, in particular those suffering from pain associated with vascular compression of a trigeminal nerve. However, carbamazepine has failed in clinical trials for other neuropathic pain conditions, even those associated with peripheral nerve compression injuries. Carbamazepine is both a GABAA receptor (GAR) agonist and a blocker of voltage-gated Na+ channels (VGSC), and our recent data suggest that differences between trigeminal and somatic nerves with respect to the VGSC present are not sufficient to account for the therapeutic selectivity of carbamazepine. Therefore, we hypothesized that these observations reflected a differential involvement of GARs in somatic and trigeminal nerves. To test this, we employed a combination of electrophysiological and behavioral experiments in rat models of somatic (sciatic nerve, SN) and trigeminal (infraorbital nerve, ION) nerve compression (CCI). We observed that the potency of carbamazepine-induced compound action potential (CAP) block was increased by CCI of the ION but not the SN, and this increase in potency was reduced by the GAR blocker picrotoxin. The potency of the GAR agonist muscimol-induced block of the ION was greater than the SN, and CCI produced a further increase in efficacy. The GABAA-rho subunit mRNA and protein was increased by CCI of the ION, but not SN. The GABAA-rho receptor selective antagonist TPMPA reduced carbamazepine-induced CAP block of the ION. CCI was also associated with an increase in the potency of the GABAA-rho receptor preferring agonist TACA-induced block of the ION, but not SN. Finally, local administration of TACA to the ION but not SN, dose-dependently reversed CCI-induced mechanical sensitivity. Taken altogether, our results suggest GABAA-rho receptors are present and functional in ION, but not SN. This differential distribution of GABAA receptors could account for the therapeutic selectivity of carbamazepine for the treatment of TN. The work was supported by generous donations from TN patients and family members as well as NIH grant R01NS064988.