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Turkish Journal of Medical Sciences 2023Neuropathic pain (NP) is a type of chronic pain usually caused by damage to the somatosensory system. Bioactive antioxidant compounds, such as curcumin and ginger, are...
BACKGROUND/AIM
Neuropathic pain (NP) is a type of chronic pain usually caused by damage to the somatosensory system. Bioactive antioxidant compounds, such as curcumin and ginger, are widely preferred in the treatment of NP. However, the ingredient-based mechanism that underlies their pain-relieving activity remains unknown. The aim of this study was to investigate the therapeutic effects of trans-[6]-Shogaol and [6]-Gingerol active ingredients of the Roscoe extract on the spinal cord and cortex in the neuroinflammatory pathway in rats with experimental sciatic nerve injury.
MATERIALS AND METHODS
Forty-six volatile phenolic components were identified in ginger samples using gas chromatography-mass spectrometry analysis. Thirty 3-month-old male 250-300 g Wistar Albino rats were divided into three groups as (i) sham, (ii) chronic constriction injury (CCI), and (iii) CCI+ginger. NP was induced using the CCI model. A ginger extract treatment enriched with trans-[6]-shogaol and [6]-gingerol active ingredients was administered by gavage at 200 mg/kg/day for 7 days. On the 14th day of the experiment, locomotor activity was evaluated in open field and hyperalgesia in tail flick tests.
RESULTS
In behavioural experiments, a significant decrease was observed in the CCI group compared to the sham group, while a significant increase was observed in the CCI+ginger group compared to the CCI group (p < 0.05). In the spinal cord and cortex tissues, there was a significant increase in the TNF-α, IL-1β, and IL-18 neuroinflammation results of the CCI group compared to the sham group, while there was a significant decrease in the CCI+ginger group compared to the CCI group.
CONCLUSION
In this study, ginger treatment was shown to have a therapeutic effect on neuroinflammation against sciatic nerve damage.
Topics: Animals; Fatty Alcohols; Catechols; Neuralgia; Rats; Male; Rats, Wistar; Zingiber officinale; Disease Models, Animal; Cytokines; Plant Extracts; Sciatic Nerve; Spinal Cord
PubMed: 38813490
DOI: 10.55730/1300-0144.5728 -
Biological Research May 2024Studies have suggested that endoplasmic reticulum stress (ERS) is involved in neurological dysfunction and that electroacupuncture (EA) attenuates neuropathic pain (NP)...
Studies have suggested that endoplasmic reticulum stress (ERS) is involved in neurological dysfunction and that electroacupuncture (EA) attenuates neuropathic pain (NP) via undefined pathways. However, the role of ERS in the anterior cingulate cortex (ACC) in NP and the effect of EA on ERS in the ACC have not yet been investigated. In this study, an NP model was established by chronic constriction injury (CCI) of the left sciatic nerve in rats, and mechanical and cold tests were used to evaluate behavioral hyperalgesia. The protein expression and distribution were evaluated using western blotting and immunofluorescence. The results showed that glucose-regulated protein 78 (BIP) and inositol-requiring enzyme 1α (IRE-1α) were co-localized in neurons in the ACC. After CCI, BIP, IRE-1α, and phosphorylation of IRE-1α were upregulated in the ACC. Intra-ACC administration of 4-PBA and Kira-6 attenuated pain hypersensitivity and downregulated phosphorylation of IRE-1α, while intraperitoneal injection of 4-PBA attenuated hyperalgesia and inhibited the activation of P38 and JNK in ACC. In contrast, ERS activation by intraperitoneal injection of tunicamycin induced behavioral hyperalgesia in naive rats. Furthermore, EA attenuated pain hypersensitivity and inhibited the CCI-induced overexpression of BIP and pIRE-1α. Taken together, these results demonstrate that EA attenuates NP by suppressing BIP- and IRE-1α-mediated ERS in the ACC. Our study presents novel evidence that ERS in the ACC is implicated in the development of NP and provides insights into the molecular mechanisms involved in the analgesic effect of EA.
Topics: Animals; Electroacupuncture; Gyrus Cinguli; Neuralgia; Male; Rats, Sprague-Dawley; Endoplasmic Reticulum Stress; Disease Models, Animal; Rats; Blotting, Western; Heat-Shock Proteins; Protein Serine-Threonine Kinases; Hyperalgesia; Endoplasmic Reticulum Chaperone BiP
PubMed: 38812057
DOI: 10.1186/s40659-024-00511-3 -
Journal of Neuroinflammation May 2024Since the 1990s, evidence has accumulated that macrophages promote peripheral nerve regeneration and are required for enhancing regeneration in the conditioning lesion...
Neither injury induced macrophages within the nerve, nor the environment created by Wallerian degeneration is necessary for enhanced in vivo axon regeneration after peripheral nerve injury.
BACKGROUND
Since the 1990s, evidence has accumulated that macrophages promote peripheral nerve regeneration and are required for enhancing regeneration in the conditioning lesion (CL) response. After a sciatic nerve injury, macrophages accumulate in the injury site, the nerve distal to that site, and the axotomized dorsal root ganglia (DRGs). In the peripheral nervous system, as in other tissues, the macrophage response is derived from both resident macrophages and recruited monocyte-derived macrophages (MDMs). Unresolved questions are: at which sites do macrophages enhance nerve regeneration, and is a particular population needed.
METHODS
Ccr2 knock-out (KO) and Ccr2 knock-in/KO mice were used to prevent MDM recruitment. Using these strains in a sciatic CL paradigm, we examined the necessity of MDMs and residents for CL-enhanced regeneration in vivo and characterized injury-induced nerve inflammation. CL paradigm variants, including the addition of pharmacological macrophage depletion methods, tested the role of various macrophage populations in initiating or sustaining the CL response. In vivo regeneration, measured from bilateral proximal test lesions (TLs) after 2 d, and macrophages were quantified by immunofluorescent staining.
RESULTS
Peripheral CL-enhanced regeneration was equivalent between crush and transection CLs and was sustained for 28 days in both Ccr2 KO and WT mice despite MDM depletion. Similarly, the central CL response measured in dorsal roots was unchanged in Ccr2 KO mice. Macrophages at both the TL and CL, but not between them, stained for the pro-regenerative marker, arginase 1. TL macrophages were primarily CCR2-dependent MDMs and nearly absent in Ccr2 KO and Ccr2 KO mice. However, there were only slightly fewer Arg1 macrophages in CCR2 null CLs than controls due to resident macrophage compensation. Zymosan injection into an intact WT sciatic nerve recruited Arg1 macrophages but did not enhance regeneration. Finally, clodronate injection into Ccr2 KO CLs dramatically reduced CL macrophages. Combined with the Ccr2 KO background, depleting MDMs and TL macrophages, and a transection CL, physically removing the distal nerve environment, nearly all macrophages in the nerve were removed, yet CL-enhanced regeneration was not impaired.
CONCLUSIONS
Macrophages in the sciatic nerve are neither necessary nor sufficient to produce a CL response.
Topics: Animals; Macrophages; Mice; Nerve Regeneration; Wallerian Degeneration; Receptors, CCR2; Peripheral Nerve Injuries; Mice, Inbred C57BL; Mice, Knockout; Sciatic Neuropathy; Axons; Mice, Transgenic; Disease Models, Animal; Sciatic Nerve; Ganglia, Spinal; Green Fluorescent Proteins
PubMed: 38802868
DOI: 10.1186/s12974-024-03132-5 -
Frontiers in Oncology 2024We report an unusual constellation of diseases in a 32-year-old woman with neurofibromatosis type 1 (NF1) diagnosed with the recently described precursor entity of...
Case report: Atypical neurofibromatous neoplasm with uncertain biological potential of the sciatic nerve and a widespread arteriovenous fistula mimicking a malignant peripheral nerve tumor in a young patient with neurofibromatosis type 1.
We report an unusual constellation of diseases in a 32-year-old woman with neurofibromatosis type 1 (NF1) diagnosed with the recently described precursor entity of malignant peripheral nerve sheath tumor (MPNST), the so-called atypical neurofibromatous neoplasm with unknown biological potential (ANNUBP) and a large symptomatic cervical arteriovenous fistula. An [F] 2-Fluoro-2-deoxy-D-glucose PET/CT (FDG-PET/CT) was performed to detect and stage a conspicuous symptomatic cervical tumor. The FDG-PET/CT showed high FDG uptake in one of the multiple known tumorous lesions associated with peripheral nerves. However, no relevant FDP uptake was observed in this affected cervical area. After digital subtraction angiography, the cervical mass turned out to be a widespread arteriovenous fistula of the vertebral artery. This was successfully treated using endovascular embolization. Subsequently, magnet resonance imaging (MRI) of the FDG-positive tumor revealed a well-enhanced homogeneous mass of the sciatic nerve measuring 5.2×2.4×2.8 cm. Microsurgical gross total tumor resection was performed using ultrasound. The final histopathological diagnosis was ANNUBP transformed from neurofibroma. The patient benefited excellently from the surgery; no recurrence or metastasis has been observed since resection. According to imaging, ANNUBP can be characterized as a well-enhanced homogeneous mass on MRI, displaying high uptake on FDG-PET/CT and hypoechogenic in ultrasound.
PubMed: 38800392
DOI: 10.3389/fonc.2024.1391456 -
BioRxiv : the Preprint Server For... May 2024Mechanical loading is required for bone health and results in skeletal adaptation to optimize strength. Local nerve axons, particularly within the periosteum, may...
Mechanical loading is required for bone health and results in skeletal adaptation to optimize strength. Local nerve axons, particularly within the periosteum, may respond to load-induced biomechanical and biochemical cues. However, their role in the bone anabolic response remains controversial. We hypothesized that spatial alignment of periosteal nerves with sites of load-induced bone formation would clarify this relationship. To achieve this, we developed RadialQuant, a custom tool for spatial histomorphometry. Tibiae of control and neurectomized (sciatic/femoral nerve cut) pan-neuronal Baf53b-tdTomato reporter mice were loaded for 5-days. Bone formation and periosteal nerve axon density were then quantified simultaneously in non-decalcified sections of the mid-diaphysis using RadialQuant. In control animals, anabolic loading induced maximal periosteal bone formation at the site of peak compression, as has been reported previously. Loading did not significantly change overall periosteal nerve density. However, a trending 28% increase in periosteal axons was noted at the site of peak compression in loaded limbs. Neurectomy depleted 88% of all periosteal axons, with near-total depletion on load-responsive surfaces. Neurectomy alone also caused de novo bone formation on the lateral aspect of the mid-diaphysis. However, neurectomy did not inhibit load-induced increases in periosteal bone area, mineralizing surface, or bone formation rate. Rather, neurectomy spatially redistributed load-induced bone formation towards the lateral tibial surface with a reduction in periosteal bone formation at the posterolateral apex (-63%) and enhancement at the lateral surface (+1360%). Altogether, this contributed to comparable load-induced changes in cortical bone area fraction (+4.4% in controls; +5.4% in neurectomized). Our results show that local skeletal innervation modulates but is not required for skeletal adaptation to applied load. This supports the continued use of loading and weight-bearing exercise as an effective strategy to increase bone mass, even in patients with peripheral nerve damage or dysfunction.
PubMed: 38798585
DOI: 10.1101/2024.05.12.593761 -
Journal of Personalized Medicine Apr 2024Simulating the post-traumatic continuity defect of small human peripheral nerves, we compared the effectiveness of fibrin glue with neurorrhaphy for nerve gap...
BACKGROUND
Simulating the post-traumatic continuity defect of small human peripheral nerves, we compared the effectiveness of fibrin glue with neurorrhaphy for nerve gap restoration.
METHODS
In twenty-four male Wistar rats, a fifteen mm defect in one sciatic nerve only was made and immediately repaired with an inverted polarity autograft. According to the used technique, rats were divided into Group A (Control), using traditional neurorrhaphy, and Group B (Study), using fibrine glue sealing; in total, 50% of rats were sacrificed at 16 weeks and 50% at 21 weeks. Before sacrifice, an assessment of motor function was done through Walking Track Analysis and an electroneurophysiological evaluation. After sacrifice, selected muscle mass indexes and the histology of the regenerated nerves were assessed. All data were evaluated by Student's test for unpaired data.
RESULTS
No significant differences were found between the two groups, with only the exception of a relative improvement in the tibialis anterior muscle's number of motor units in the study group.
CONCLUSION
Despite the fact that the use of fibrin glue as a nerve sealant is not superior in terms of functional recovery, its effectiveness is comparable to that of microsurgical repair. Hence, the faster and technically easier glueing technique could deserve broader clinical application.
PubMed: 38793027
DOI: 10.3390/jpm14050445 -
Medicina (Kaunas, Lithuania) Apr 2024: The number of hip arthroscopy procedures is on the rise worldwide, and awareness regarding proper management of the hip capsule has increased. No capsulotomy shape is...
: The number of hip arthroscopy procedures is on the rise worldwide, and awareness regarding proper management of the hip capsule has increased. No capsulotomy shape is agreed upon as a standard approach, with literature supporting both isolated interportal and T-shaped capsulotomies. The aim of this retrospective cohort study is to report the clinical results of a standardized extended interportal capsulotomy (EIPC) during hip arthroscopy. : Patients operated on between 2017 and 2020 with a hip arthroscopy were eligible. The inclusion criteria were ages 18-60 years, failed non-operative treatment, and at least a 2-year follow-up. Exclusion criteria were bilateral femoroacetabular impingement syndrome (FAS) cases or labral lesions, ipsilateral knee injury, history of ipsilateral hip surgery, and significant spine lesions. Data regarding demographic characteristics such as age, gender, operation date, BMI, but also Beighton score, presence of postoperative pudendal nerve damage, and revision for any reason were gathered from patients' records. All patients were evaluated preoperatively with a visual analog scale (VAS), the Hip Disability and Osteoarthritis Outcome Score (HOOS), and the modified Harris Hip Score (mHHS). : Of the 97 patients operated on with a hip arthroscopy between the defined dates, only 90 patients were included. The mean age was 37.9 ± 9.8, and 58.9% of patients were male. The most frequent surgical indication was an isolated FAS lesion (73.3%), followed by FAS associated with a labral tear (12.2%), an isolated labrum tear (10.0%), synovitis (3.3%), and a loose body (1.1%). The mean follow-up for the study cohort was 39.3 months. The majority of the patients had uneventful surgeries (76.7%), while there were three cases of sciatic nerve neuropraxia and 12 cases of pudendal nerve neuropraxia. Two patients underwent revision surgery during the study period. Comparison between preoperative and postoperative clinical scores showed a significant improvement with a final mHHS mean value of 67.7 ± 18.2, an HOOS value of 74.1 ± 13.2, and a low VAS score of 1.3 ± 1.2. : A hip arthroscopy procedure with a standardized and unrepaired, extended interportal capsulotomy is a safe procedure with satisfactory mid-term results and high overall patient satisfaction. At a minimum of 2 years and a mean of 39.2 months, patients showed improved clinical scores and a low revision rate.
Topics: Humans; Adult; Male; Female; Retrospective Studies; Middle Aged; Arthroscopy; Hip Joint; Adolescent; Joint Capsule; Treatment Outcome; Cohort Studies; Young Adult; Femoracetabular Impingement
PubMed: 38792921
DOI: 10.3390/medicina60050738 -
Medicina (Kaunas, Lithuania) Apr 2024: This review systematically evaluates the potential of electrical neuromodulation techniques-vagus nerve stimulation (VNS), sacral nerve stimulation (SNS), and tibial... (Review)
Review
: This review systematically evaluates the potential of electrical neuromodulation techniques-vagus nerve stimulation (VNS), sacral nerve stimulation (SNS), and tibial nerve stimulation (TNS)-as alternative treatments for inflammatory bowel disease (IBD), including ulcerative colitis (UC) and Crohn's Disease (CD). It aims to synthesize current evidence on the efficacy and safety of these modalities, addressing the significant burden of IBD on patient quality of life and the limitations of existing pharmacological therapies. : We conducted a comprehensive analysis of studies from PubMed, focusing on research published between 1978 and 2024. The review included animal models and clinical trials investigating the mechanisms, effectiveness, and safety of VNS, SNS, and TNS in IBD management. Special attention was given to the modulation of inflammatory responses and its impact on gastrointestinal motility and functional gastrointestinal disorders associated with IBD. : Preliminary findings suggest that VNS, SNS, and TNS can significantly reduce inflammatory markers and improve symptoms in IBD patients. These techniques also show potential in treating related gastrointestinal disorders during IBD remission phases. However, the specific mechanisms underlying these benefits remain to be fully elucidated, and there is considerable variability in treatment parameters. : Electrical neuromodulation holds promise as a novel therapeutic avenue for IBD, offering an alternative to patients who do not respond to traditional treatments or experience adverse effects. The review highlights the need for further rigorous studies to optimize stimulation parameters, understand long-term outcomes, and integrate neuromodulation effectively into IBD treatment protocols.
Topics: Humans; Inflammatory Bowel Diseases; Electric Stimulation Therapy; Animals; Vagus Nerve Stimulation; Tibial Nerve; Quality of Life
PubMed: 38792911
DOI: 10.3390/medicina60050729 -
Medicina (Kaunas, Lithuania) Apr 2024: The interspace between the popliteal artery and the posterior capsule of the knee (iPACK) block has been widely used in perioperative settings to control posterior...
Investigation of Optimal Needle Position for Radiofrequency Ablation-Based Blockade of Interspace between the Popliteal Artery and the Posterior Capsule of the Knee: A Cadaveric Study.
: The interspace between the popliteal artery and the posterior capsule of the knee (iPACK) block has been widely used in perioperative settings to control posterior knee pain and can additionally be used for chronic knee pain. In this cadaveric study, we aimed to investigate the needle tip position and its proximity to the articular branch of the tibial nerve (ABTN) during an iPACK-targeted radiofrequency procedure. : An ultrasound-guided iPACK block was performed on 20 knees of 10 cadavers. We injected 0.1 mL each of blue and green gelatinous dye near the tibial artery (point A) and posterior knee capsule (point B), respectively, and evaluated the spread of both around the ABTN. For a hypothetical conventional radiofrequency ablation (RFA) lesion (diameter, 2.95 mm) and cooled RFA lesion (diameter, 4.9 mm), we counted the number of specimens in which the ABTNs would be captured. : The percentage of specimens in which the ABTN would be captured by a cooled RFA lesion was 64.71% at point A and 43.75% at point B ( = 0.334). Meanwhile, the percentage of specimens in which the ABTN would be captured by a conventional RFA lesion was 58.82% from point A and 25% from point B ( = 0.065). : When performing an RFA-based iPACK block, the needle tip may be positioned either lateral to the tibial artery or in the space between the posterior knee capsule and the tibial artery. However, more studies with larger samples are needed to verify these results before the clinical use of this procedure can be recommended.
Topics: Humans; Cadaver; Popliteal Artery; Radiofrequency Ablation; Female; Male; Nerve Block; Needles; Aged; Knee Joint; Aged, 80 and over; Tibial Nerve; Ultrasonography, Interventional
PubMed: 38792872
DOI: 10.3390/medicina60050689 -
Journal of Nanobiotechnology May 2024Endothelial cell (EC)-driven intraneural revascularization (INRV) and Schwann cells-derived exosomes (SCs-Exos) both play crucial roles in peripheral nerve injury (PNI)....
BACKGROUND
Endothelial cell (EC)-driven intraneural revascularization (INRV) and Schwann cells-derived exosomes (SCs-Exos) both play crucial roles in peripheral nerve injury (PNI). However, the interplay between them remains unclear. We aimed to elucidate the effects and underlying mechanisms of SCs-Exos on INRV following PNI.
RESULTS
We found that GW4869 inhibited INRV, as well as that normoxic SCs-Exos (N-SCs-Exos) exhibited significant pro-INRV effects in vivo and in vitro that were potentiated by hypoxic SCs-Exos (H-SCs-Exos). Upregulation of glycolysis emerged as a pivotal factor for INRV after PNI, as evidenced by the observation that 3PO administration, a glycolytic inhibitor, inhibited the INRV process in vivo and in vitro. H-SCs-Exos more significantly enhanced extracellular acidification rate/oxygen consumption rate ratio, lactate production, and glycolytic gene expression while simultaneously suppressing acetyl-CoA production and pyruvate dehydrogenase E1 subunit alpha (PDH-E1α) expression than N-SCs-Exos both in vivo and in vitro. Furthermore, we determined that H-SCs-Exos were more enriched with miR-21-5p than N-SCs-Exos. Knockdown of miR-21-5p significantly attenuated the pro-glycolysis and pro-INRV effects of H-SCs-Exos. Mechanistically, miR-21-5p orchestrated EC metabolism in favor of glycolysis by targeting von Hippel-Lindau/hypoxia-inducible factor-1α and PDH-E1α, thereby enhancing hypoxia-inducible factor-1α-mediated glycolysis and inhibiting PDH-E1α-mediated oxidative phosphorylation.
CONCLUSION
This study unveiled a novel intrinsic mechanism of pro-INRV after PNI, providing a promising therapeutic target for post-injury peripheral nerve regeneration and repair.
Topics: Schwann Cells; Exosomes; Animals; Glycolysis; Endothelial Cells; Mice; Peripheral Nerve Injuries; Male; Rats; MicroRNAs; Mice, Inbred C57BL; Neovascularization, Physiologic; Rats, Sprague-Dawley; Aniline Compounds; Benzylidene Compounds
PubMed: 38789980
DOI: 10.1186/s12951-024-02536-y