Photobiomodulation inhibits neuronal firing in the superficial but not deep layer of a rat spinal dorsal horn.

Photobiomodulation (PBM) has attracted attention as a treatment for chronic pain. Previous studies have reported that PBM of the sciatic nerve inhibits neuronal firing in the superficial layers (lamina I-II) of the spinal dorsal horn of rats, which is evoked by mechanical stimulation that corresponds to noxious stimuli. However, the effects of PBM on the deep layers (lamina III-IV) of the spinal dorsal horn, which receive inputs from innocuous stimuli, remain poorly understood. In this study, we examined the effect of PBM of the sciatic nerve on firing in the deep layers of the spinal dorsal horn evoked by mechanical stimulation. Before and after PBM, mechanical stimulation was administered to the cutaneous receptive field using 0.6-26.0 g von Frey filaments (vFFs), and vFF-evoked firing in the deep layers of the spinal dorsal horn was recorded. The vFF-evoked firing frequencies were not altered after the PBM for any of the vFFs. The inhibition rate for 26.0 g vFF-evoked firing was approximately 13 % in the deep layers and 70 % in the superficial layers. This suggests that PBM selectively inhibits the transmission of pain information without affecting the sense of touch. PBM has the potential to alleviate pain while preserving the sense of touch.

[Effects of tetramethylpyrazine on pharmacokinetics in plasma and brain dialysate and neuropathic pain in rat model of spared sciatic nerve injury].

This study aims to explore the effects of tetramethylpyrazine(TMP) on pharmacokinetics in plasma and brain dialysate and neuropathic pain in the rat model of partial sciatic nerve injury(SNI), and to investigate the correlation between the analgesic effect of TMP and its concentrations in the plasma and brain dialysate. Male SD rats were randomized into Sham, SNI, and SNI+TMP groups. Mechanical stimulation with von frey filaments and cold spray method were employed to evaluate the mechanical sensitivity and cold sensitivity of rats. Another two groups, Sham+TMP and SNI+TMP, were used to intubate the common jugular vein and implant microdialysis probes into the anterior cingulate gyrus(ACC), respectively.After intraperitoneal injection of TMP at a dose of 80 mg·kg~(-1), automatic blood collection and intracerebral microdialysis(perfusion rate of 1 µL·min~(-1)) systems were used to collect the blood and brain dialysate for 24 h. HSS T3 C_(18) reversed-phase chromatographic column(2.1 mm×50 mm, 2.5 µm) was used for liquid chromatographic separation. Gradient elution was carried out with the mobile phase of methanol-water(containing 0.005% formic acid) at a flow rate of 0.25 mL·min~(-1). Electrospray ion source was used for mass spectrometry, and the scanning mode was multi-reaction monitoring under the positive ion mode. The ion pairs for quantitative analysis were TMP m/z 137/122 and aspirin m/z 179/137, respectively. DAS 2.11 was used to calculate the pharmacokinetic parameters. The optimal time of TMP to exert the analgesia effect and inhibit cold pain sensitivity was 60 min after treatment. The TMP in the plasma and brain dialysate of SNI rats showed the T_(max) of 15 min and 30 min, the C_(max) of(2 866.43±135.39) and(1 462.14±197.38) µg·L~(-1), the AUC_(0-t) of(241 463.30±28 070.31) and(213 115.62±32 570.07) µg·min·L~(-1), the MRT_(0-t) of(353.13±47.73) and(172.16±12.72) min, and the CL_Z of 0.73 and 0.36 L·min·kg~(-1), respectively. The analgesic effect of TMP had a significant correlation with the blood drug concentration in the ACC, which indicated that this method was suitable for the detection of TMP in rat plasma and brain dialysate. The method is accurate, reliable, and sensitive and can realize the important value of the application of correlation analysis theory of "automatic blood collection-microdialysis/PK-PD" in the research on neuropathic pain.

Electroacupuncture improves peripheral neuropathy by up-regulating Sirt1/PGC-1α/TFAM pathway in type 2 diabetes rats with peripheral neuropathy. / 基于Sirt1/PGC-1α/TFAM通路探讨电针治疗2åž‹ç³–å°¿ç— å‘¨å›´ç¥žç»ç— å˜çš„æœºåˆ¶.

OBJECTIVES: To observe the effect of electroacupuncture (EA) on activation of silent information regulator 1 (Sirt1)/peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α)/mitochondrial transcription factor A (TFAM) pathway in type 2 diabetes (T2DM) rats with peripheral neuropathy (DPN) , so as to explore its possible mechanisms underlying improvement of DPN. METHODS: Thirty male SD rats were randomly divided into blank control group (n=8) and DPN model group (n=22) which were further divided into model group (n=8) and EA group (n=8) after successful modeling. The model of T2DM was established by high-fat diet and low-dose intraperitoneal injection of streptozocin (35 mg/kg). For rats of the EA group (anesthetized with isoflurane), EA stimulation (2 Hz/15 Hz, 2 mA) was applied to "Tianshu"(ST25) for 20 min, once daily, 6 times a week for 6 weeks. The blood glucose level, body weight, area under curve (AUC) of glucose tolerance test, and hind-paw mechanical pain threshold and thermal pain threshold were observed. The intra-epidermal nerve fiber density (IENFD) of the hind-foot pad was observed by immunofluorescence staining. The motor nerve conduction velocity (MNCV) of the sciatic nerve was measured by using electrophysiological method. H.E. staining was used to observe the histopathological changes of the sciatic nerve after modeling. Transmission electron microscopy (TEM) was used to observe the ultrastructural changes of the sciatic nerve. The protein expressions of energy-related Sirt1, PGC-1α and TFAM in the sciatic nerve was detected by Western blot. RESULTS: Compared with the blank control group, the model group had a higher blood glucose contents and AUC (P<0.001), a slower MNCV (P<0.01), and a decrease in the body weight and in the mechanical and thermal pain thresholds (P<0.001) and IENFD (P<0.001), and in the expression levels of Sirt1, PGC-1α and TFAM (P<0.05, P<0.01). In contrast to the model group, the EA group had a decrease in the blood glucose contents and AUC (P<0.05, P<0.01), and an increase in mechanical and thermal pain thresholds, MNCV, IENFD, and expression levels of Sirt1, PGC-1α and TFAM proteins (P<0.01, P<0.05). In addition, results of histopathological and ultrastructural changes of the sciatic nerve showed more fragmented and disordered distribution of axons on the transverse section, and extensive separation of myelin and axons, uneven myelin thickness, axonal degeneration and irregular shape in the model group, whereas in the EA group, the axons on the transverse section were relatively more dense and more complete, the myelin sheath of the sciatic nerve was relatively uniform, and the axonal shape was relatively regular with relatively milder lesions. CONCLUSIONS: EA up-regulates the expressions of Sirt1, PGC-1α, TFAM in T2DM rats with DPN, which may be associated with its functions in improving and repairing the injured peripheral nerves in rats with DPN.

Research progress of traditional Chinese medicine monomer in treating diabetic peripheral neuropathy: A review.

Diabetes peripheral neuropathy is one of the most common complications of diabetes. Early symptoms are insidious, while late symptoms mainly include numbness, pain, swelling, and loss of sensation in the limbs, which can lead to disability, foot ulcers, amputation, and so on. At present, the pathogenesis is also complex and diverse, and it is not yet clear. Western medicine treatment mainly focuses on controlling blood sugar and nourishing nerves, but the effect is not ideal. In recent years, it has been found that many drug monomers have shown good therapeutic and prognostic effects in the prevention and treatment of diabetes peripheral neuropathy, and related research has become a hot topic. To understand the specific mechanism of action of traditional Chinese medicine monomers in treatment, this article provides a review of their mechanism research and key roles. It mainly includes flavonoids, phenols, terpenes, saponins, alkaloids, polysaccharides, etc. By nuclear factor-κB (NF-κB), the signaling pathways of adenosine monophosphate-activated protein kinase (AMPK), Nrf2/ARE, SIRT1/p53, etc, can play a role in lowering blood sugar, antioxidant, anti-inflammatory, inhibiting cell apoptosis, and autophagy, promoting sciatic nerve regeneration, and have great potential in the prevention and treatment of this disease. A systematic summary of its related mechanisms of action was conducted, providing ideas for in-depth research and exploration of richer traditional Chinese medicine components, and also providing a relatively complete theoretical reference for clinical research on diabetes peripheral neuropathy treatment.

NTPDase1-ATP-P2Y2Rs axis in the sciatic nerve contributes to acupuncture at "Zusanli" (ST36)-induced analgesia in ankle arthritis rats.

BACKGROUND: The efficacy of acupuncture at Zusanli (ST36) in alleviating lower-limb pain is widely acknowledged in clinical practice, while its underlying mechanism remains incompletely elucidated. Our previous research had revealed that the prompt analgesia induced by needling-ST36 was accompanied by expression alterations in certain exco-nucleotidases within the sciatic nerve. Building upon this finding, the current work focused on NTPDase1, the primary ecto-nucleotidase in the human body, which converts ATP into AMP. METHODS: A 20-min acupuncture was administered unilaterally at the ST36 on rats with acute ankle arthritis. The pain thresholds of the injured hind paws were determined. Pharmacological interference was carried out by introducing the corresponding reagents to the sciatic nerve. ATP levels around the excised nerve were measured using a luciferase-luciferin assay. Live calcium imaging, utilizing the Fura 2-related-F340/F380 ratio, was conducted on Schwann cells in excised nerves and cultured rat SCs line, RSC96 cells. RESULTS: The analgesic effect induced by needling-ST36 was impaired when preventing ATP degradation via inhibiting NTPDase1 activities with ARL67156 or Ticlopidine. Conversely, increasing NTPDase1 activities with Apyrase duplicated the acupuncture effect. Similarly, preventing the conversion of AMP to adenosine via suppression of NT5E with AMP-CP hindered the acupuncture effect. Unexpectedly, impeded ATP hydrolysis ability and diminished NTPDase1 expression were observed in the treated group. Agonism at P2Y2Rs with ATP, UTP, or INS365 resulted in anti-nociception. Contrarily, antagonism at P2Y2Rs with Suramin or AR-C 118925xx prevented acupuncture analgesia. Immunofluorescent labeling demonstrated that the treated rats expressed more P2Y2Rs that were predominant in Schwann cells. Suppression of Schwann cells by inhibiting ErbB receptors also prevented acupuncture analgesia. Finally, living imaging on the excised nerves or RSC96 cells showed that agonism at P2Y2Rs indeed led to [Ca2+]i rise. CONCLUSION: These findings strongly suggest that the analgesic mechanism of needling-ST36 on the hypersensation in the lower limb partially relies on NTPDase1 activities in the sciatic nerve. In addition to facilitating adenosine signaling in conjunction with NT5E, most importantly, NTPDase1 may provide an appropriate low-level ATP milieu for the activation of P2Y2R in the sciatic nerve, particularly in Schwann cells.

TsMS combined with EA promotes functional recovery and axonal regeneration via mediating the miR-539-5p/Sema3A/PlexinA1 signalling axis in sciatic nerve-injured rats.

Enhancing axonal regeneration is one of the most important processes in treating nerve injuries. Both magnetic and electrical stimulation have the effect of promoting nerve axon regeneration. But few study has investigated the effects of trans-spinal magnetic stimulation (TsMS) combined with electroacupuncture (EA) on nerve regeneration in rats with sciatic nerve injury. In this study, we compared the improvement of neurological function in rats with sciatic nerve crush injuries after 4 weeks of different interventions (EA, TsMS, or TsMS combined with EA). We further explored the morphological and molecular biological alterations following sciatic nerve injury by HE, Masson, RT-PCR, western blotting, immunofluorescence staining and small RNA transcriptome sequencing. The results showed that TsMS combined with EA treatment significantly promoted axonal regeneration, increased the survival rate of neurons, and suppressed denervation atrophy of the gastrocnemius muscle. Subsequent experiments suggested that the combination treatment may play an active role by mediating the miR-539-5p/Sema3A/PlexinA1 signaling axis.

Therapeutic Effect of an Ursolic Acid-Based Nutraceutical on Neuronal Regeneration after Sciatic Nerve Injury.

Peripheral nerve injuries lead to severe functional impairments and long recovery times, with limited effectiveness and accessibility of current treatments. This has increased interest in natural bioactive compounds, such as ursolic acid (UA). Our study evaluated the effect of an oleolyte rich in UA from white grape pomace (WGPO) on neuronal regeneration in mice with induced sciatic nerve resection, administered concurrently with the induced damage (the WGPO group) and 10 days prior (the PRE-WGPO group). The experiment was monitored at two-time points (4 and 10 days) after injury. After 10 days, the WGPO group demonstrated a reduction in muscle atrophy, evidenced by an increased number and diameter of muscle fibers and a decreased Atrogin-1 and Murf-1 expression relative to the denervated control. It was also observed that 85.7% of neuromuscular junctions (NMJs) were fully innervated, as indicated by the colocalization of α-bungarotoxin and synaptophysin, along with the significant modulation of Oct-6 and S-100. The PRE-WGPO group showed a more beneficial effect on nerve fiber reformation, with a significant increase in myelin protein zero and 95.2% fully innervated NMJs, and a pro-hypertrophic effect in resting non-denervated muscles. Our findings suggest WGPO as a potential treatment for various conditions that require the repair of nerve and muscle injuries.

RTA-408 Regulates p-NF-κB/TSLP/STAT5 Signaling to Ameliorate Nociceptive Hypersensitivity in Chronic Constriction Injury Rats.

Neuropathic pain following nerve injury is a complex condition, which often puts a negative impact on life and remains a sustained problem. To make pain management better is of great significance and unmet need. RTA 408 (Omaveloxone) is a traditional Asian medicine with a valid anti-inflammatory property. Thus, we aim to investigate the therapeutic effect of RTA-408 on mechanical allodynia in chronic constriction injury (CCI) rats as well as the underlying mechanisms. Neuropathic pain was induced by using CCI of the rats' sciatic nerve (SN) and the behavior testing was measured by calibrated forceps testing. Activation of Nrf-2, the phosphorylation of nuclear factor-κB (NF-κB), and the inflammatory response were assessed by western blots. The number of apoptotic neurons and degree of glial cell reaction were examined by immunofluorescence assay. RTA-408 exerts an analgesic effect on CCI rats. RTA-408 reduces neuronal apoptosis and glial cell activation by increasing Nrf-2 expression and decreasing the inflammatory response (TNF-α/ p-NF-κB/ TSLP/ STAT5). These data suggest that RTA-408 is a candidate with potential to reduce nociceptive hypersensitivity after CCI by targeting TSLP/STAT5 signaling.

Electroacupuncture Promotes Nerve Regeneration and Functional Recovery Through Regulating lncRNA GAS5 Targeting miR-21 After Sciatic Nerve Injury.

Although the benefits of electroacupuncture (EA) for peripheral nerve injury (PNI) are well accepted in clinical practice, the underlying mechanism remains incompletely elucidated. In our study, we observed that EA intervention led to a reduction in the expression of the long non-coding RNA growth-arrest-specific transcript 5 (GAS5) and an increased in miR-21 levels within the injured nerve, effectively promoting functional recovery and nerve regeneration following sciatic nerve injury (SNI). In contrast, administration of adeno-associated virus expressing GAS5 (AAV-GAS5) weakened the therapeutic effect of EA. On the other hand, both silencing GAS5 and introducing a miR-21 mimic prominently enhanced the proliferation activity and migration ability of Schwann cells (SCs), while also inhibiting SCs apoptosis. On the contrary, inhibition of SCs apoptosis was found to be mediated by miR-21. Additionally, overexpression of GAS5 counteracted the effects of the miR-21 mimic on SCs. Moreover, SCs that transfected with the miR-21 mimic promoted neurite growth in hypoxia/reoxygenation-induced neurons, which might be prevented by overexpressing GAS5. Furthermore, GAS5 was found to be widely distributed in the cytoplasm and was negatively regulated by miR-21. Consequently, the targeting of GAS5 by miR-21 represents a potential mechanism through which EA enhances reinnervation and functional restoration following SNI. Mechanistically, the GAS5/miR-21 axis can modulate the proliferation, migration, and apoptosis of SCs while potentially influencing the neurite growth of neurons.

Effect of ST36 electroacupuncture on the switch of skeletal muscle fibres in mice with sciatic nerve dissociation.

Skeletal muscle is striated muscle that moves autonomously and is innervated by peripheral nerves. Peripheral nerve injury is very common in clinical treatment. However, the commonly used treatment methods often focus on the regeneration of the injured nerve but overlook the pathological changes in the injured skeletal muscle. Acupuncture, as the main treatment for denervated skeletal muscle atrophy, is used extensively in clinical practice. In the present study, a mouse model of lower limb sciatic nerve detachment was constructed and treated with electroacupuncture Stomach 36 to observe the atrophy of lower limb skeletal muscle and changes in skeletal muscle fibre types before and after electroacupuncture Stomach 36 treatment. Mice with skeletal muscle denervation showed a decrease in the proportion of IIa muscle fibres and an increase in the proportion of IIb muscle fibres, after electroacupuncture Stomach 36. The changes were reversed by specific activators of p38 MAPK, which increased IIa myofibre ratio. The results suggest that electroacupuncture Stomach 36 can reverse the change of muscle fibre type from IIb to IIa after denervation of skeletal muscle by inhibiting p38 MAPK. The results provide an important theoretical basis for the treatment of clinical peripheral nerve injury diseases with electroacupuncture, in addition to novel insights that could facilitate the study of pathological changes of denervated skeletal muscle.

Effects of electroacupuncture at "Jiaji" (EX-B 2) combined with neurodynamic mobilization on gastrocnemius muscle atrophy and expression of NF-κB and MuRF1 in rabbits after sciatic nerve injury. / 电针"夹脊"ç»“åˆç¥žç»æ¾åŠ¨æœ¯å¯¹åéª¨ç¥žç»æŸä¼¤å ”è “è‚ è‚ŒèŽç¼©åŠNF-κB、MuRF1表达的影响.

OBJECTIVES: To observe the effects of electroacupuncture (EA) at "Jiaji" (EX-B 2) combined with neurodynamic mobilization (NM) on the cross-sectional area of the gastrocnemius muscle fibers after sciatic nerve injury in rabbits, and the expression of nuclear factor κB (NF-κB) and muscle-specific ring-finger protein 1 (MuRF1). METHODS: A total of 180 common-grade New Zealand rabbits (half male and half female) were randomly divided into five groups, i.e. a normal control group, a model control group, a NM group, an EA group and a combined intervention group, 36 rabbits in each group. Except in the normal control group, clipping method was used to prepare the model of sciatic nerve injury in the rest groups. On the 3rd day of successful modeling, NM was delivered in the NM group. In the EA group, EA was exerted at bilateral "Jiaji" (EX-B 2) of L4 to L6, stimulated with disperse-dense wave and the frequency of 2 Hz/100 Hz. In the combined intervention group, after EA delivered at bilateral "Jiaji" (EX-B 2) of L4 to L6 , NM was operated. The intervention in each group was delivered once daily, for 6 days a week, and lasted 1, 2 or 4 weeks according to the collection time of sample tissue. After 1, 2 and 4 weeks of intervention, in each group, the toe tension reflex score and the modified Tarlov test score were observed; the morphology of the gastrocnemius muscle was observed by HE staining and the cross-sectional area of muscular fiber was measured; using Western blot method, the expression of NF-κB and MuRF1 of the gastrocnemius muscle was detected. RESULTS: After 1, 2 and 4 weeks of intervention, the toe tension reflex scores and the modified Tarlov scores in the model control group were lower than those of the normal control group (P<0.05), and these two scores in the NM group, the EA group and the combined intervention group were all higher than those of the model control group (P<0.05); the scores in the combined intervention group were higher than those in the EA group and the NM group (P<0.05). The gastrocnemius fibers were well arranged and the myocyte morphology was normal in the normal control group. In the model control group, the gastrocnemius fibers were disarranged, the myocytes were irregular in morphology and the inflammatory cells were infiltrated in the local. In the NM group, the EA group and the combined intervention group, the muscle fibers were regularly arranged when compared with the model control group. After 1, 2 and 4 weeks of intervention, the cross-sectional areas of the gastrocnemius muscle fibers in the model control group were smaller than those of the normal control group (P<0.05). The cross-sectional areas in the NM group, the EA group and the combined intervention group were larger than those of the model control group (P<0.05), and the cross-sectional areas in the combined intervention group were larger than those in the NM group and the EA group (P<0.05). After intervention for 1, 2 and 4 weeks, the protein expressions of NF-κB and MuRF1 in the gastrocnemius muscle were higher in the model control group in comparison of those in the normal control group (P<0.05). In the NM group, the EA group and the combined intervention group, the expressions of NF-κB after intervention for 1, 2 and 4 weeks and the expressions of MuRF1 after 2 and 4 weeks of intervention were lower when compared with those in the model control group (P<0.05). In the combined intervention group, the protein expressions of NF-κB after intervention for 1, 2 and 4 weeks and the expressions of MuRF1 after 2 and 4 weeks of intervention were decreased when compared with those in the NM group and the EA group (P<0.05). CONCLUSIONS: Electroacupuncture at "Jiaji" (EX-B 2) combined with NM may increase the muscle strength and sciatic function and alleviate gastrocnemius muscle atrophy in the rabbits with sciatic nerve injury. The underlying mechanism is related to the inhibition of NF-κB and MuRF1 expression.

An experimental model of peripheral nerve electrical injury in rats.

INTRODUCTION: Although several studies have investigated models of nerve electrical injury, only a few have focused on electrical injury to peripheral nerves, which is a common and intractable problem in clinical practice. Here, we describe an experimental rat model of peripheral nerve electrical injury and its assessment. METHODS: A total of 120 animals were subjected to short-term corrective electrostimulation (50 Hz, 1-s duration) applied at varying voltages (control, 65, 75, 100, 125, and 150 V) to the exposed left sciatic nerve. Behavioural testing, electrophysiological measurements, and histopathological observation of the sciatic nerve were conducted at 1-, 2-, 4-, and 8-w follow-ups. RESULTS: No functional defects were noted in the groups that received 65-V stimulation at any time point. Sciatic nerve functional defects were found after 2 w in animals that received 75-V stimulation, but function returned to normal after 4 w. In animals that received 100-V and 125-V stimulation, functional defects were observed at 4 w, but had partially recovered by 8 w. Conversely, animals that received 150-V stimulation did not show recovery after 8 w. CONCLUSION: We presented a model of peripheral nerve electrical injury that avoided the interference of various external factors, such as current instability, compression of the surrounding tissues, and altered blood supply. The model allowed quantitation and ranking of the nerve injury into four degrees. It facilitated effective evaluation of nerve function impairment and repair after injury. It can be used post-surgically to evaluate peripheral nerve impairment and reconstruction and enables translational interpretation of results, which may improve understanding of the mechanisms underlying the progression of peripheral nerve electrical injury.

Acetyl-11-Keto-Beta-Boswellic Acid Activates the Nrf2/HO-1 Signaling Pathway in Schwann Cells to Reduce Oxidative Stress and Promote Sciatic Nerve Injury Repair.

Boswellia is a traditional medicine for bruises and injuries. Its main active ingredient, acetyl-11-keto-beta-boswellic acid, has antioxidant and antiapoptotic effects. In this experiment, we used Sprague-Dawley rats to make a sciatic nerve injury model to detect the transcription factor NF-E2-related factor 2/heme oxygenase 1 signaling pathway and apoptosis, combined with clinical indicators, for testing whether acetyl-11-keto-beta-boswellic acid can reduce oxidative stress and promote sciatic nerve repair. Our results showed that acetyl-11-keto-beta-boswellic acid administration promoted myelin regeneration and functional recovery in the rat sciatic nerve, reduced lipid peroxidation levels, upregulated the expression of various antioxidant enzymes and enhanced enzyme activity, decreased the expression levels of apoptosis-related proteins, and promoted nuclear translocation of the transcription factor NF-E2-related factor 2 protein. In vitro studies revealed that acetyl-11-keto-beta-boswellic acid reduced H2O2-induced reactive oxygen species production, restored mitochondrial membrane potential, upregulated the expression of various antioxidant enzymes, and downregulated apoptosis-related indicators in Schwann cells, and these therapeutic effects of acetyl-11-keto-beta-boswellic acid were reversed after ML385 treatment in Schwann cells. In summary, acetyl-11-keto-beta-boswellic acid alleviates oxidative stress and apoptosis caused by sciatic nerve injury in rats by activating the transcription factor NF-E2-related factor 2/heme oxygenase 1 signaling pathway, promotes the recovery of sciatic nerve function in rats, and is a promising therapeutic agent to promote sciatic nerve repair by alleviating excessive oxidative stress.

Investigation of the Neuro-Regenerative Effects of Bioresonance and Magnetotherapy in Sciatic Nerve Damage-Induced Rats / Investigación de los Efectos Neurorregenerativos de Biorresonancia y Magnetoterapia en Ratas Inducidas por Daño del Nervio Ciático

SUMMARY: Peripheral nerve damage is a significant clinical problem that can lead to severe complications in patients. Regarding the regeneration of peripheral nerves, it is crucial to use experimental animals' nerves and use different evaluation methods. Epineural or perineural suturing is the gold standard in treating sciatic nerve injury, but nerve repair is often unsuccessful. This study aimed to investigate the neuroregenerative effects of magnetotherapy and bioresonance in experimental animals with sciatic nerve damage. In this study, 24 female Wistar rats were divided into 7 groups (n=6) as follows: Group 1 (Control), Group 2 (Axonotmesis control), Group 3 (Anastomosis control), Group 4 (Axonotmesis + magnetotherapy), Group 5 (Anastomosis + magnetotherapy), Group 6 (Axonotmesis + bioresonance), Group 7 (Anastomosis + bioresonance). Magnetotherapy and bioresonance treatments were applied for 12 weeks. Behavioural tests and EMG tests were performed at the end of the 12th week. Then the rats were sacrificed, and a histopathological evaluation was made. The statistical significance level was taken as 5 % in the calculations, and the SPSS (IBM SPSS for Windows, ver.21) statistical package program was used for the calculations. Statistically significant results were obtained in animal behaviour tests, EMG, and pathology groups treated with magnetotherapy. There was no statistically significant difference in the groups treated with bioresonance treatment compared to the control groups. Muscle activity and nerve repair occurred in experimental animals with acute peripheral nerve damage due to 12 weeks of magnetotherapy, and further studies should support these results.

El daño a los nervios periféricos es un problema clínico importante que puede conducir a complicaciones graves en los pacientes. En cuanto a la regeneración de los nervios periféricos, es crucial utilizar los nervios de los animales de experimentación y diferentes métodos de evaluación. La sutura epineural o perineural es el gold estándar en el tratamiento de lesiones del nervio ciático, pero la reparación del nervio a menudo no tiene éxito. Este estudio tuvo como objetivo investigar los efectos neuroregenerativos de la magnetoterapia y la biorresonancia en animales de experimentación con daño del nervio ciático. En el estudio, 24 ratas hembras Wistar se dividieron en 7 grupos (n=6) de la siguiente manera: Grupo 1 (Control), Grupo 2 (Control de axonotmesis), Grupo 3 (Control de anastomosis), Grupo 4 (Axonotmesis + magnetoterapia), Grupo 5 (Anastomosis + magnetoterapia), Grupo 6 (Axonotmesis + biorresonancia), Grupo 7 (Anastomosis + biorresonancia). Se aplicaron durante 12 semanas tratamientos de magnetoterapia y biorresonancia. Las pruebas de comportamiento y las pruebas de EMG se realizaron al final de la semana 12. Luego se sacrificaron las ratas y se realizó una evaluación histopatológica. El nivel de significación estadística se tomó como 5 % en los cálculos, y se utilizó el programa de paquete estadístico SPSS (IBM SPSS para Windows, ver.21). Se obtuvieron resultados estadísticamente significativos en pruebas de comportamiento animal, EMG y grupos de patología tratados con magnetoterapia. No hubo diferencia estadísticamente significativa en los grupos con tratamiento de biorresonancia en comparación con los grupos controles. La actividad muscular y la reparación nerviosa, se produjeron en animales de experimentación con daño nervioso periférico agudo, debido a 12 semanas de magnetoterapia.Estudios adicionales deberían respaldar estos resultados.

Therapeutic effects of cinnamon bark oil on sciatic nerve injury in rats.

OBJECTIVE: The aim of this study was to investigate the effects of cinnamon bark essential oil (CBO) on analgesia, motor activity, balance, and coordination in rats with sciatic nerve damage. MATERIALS AND METHODS: Rats were divided into three groups as simply randomized. The right sciatic nerve (RSN) of the Sham group was explored. Only vehicle solution was applied for 28 days. The RSN of the sciatic nerve injury (SNI) group was explored. Damage was created by unilateral clamping, and vehicle solution was applied for 28 days. The RSN of the sciatic nerve injury+cinnamon bark essential oil (SNI+CBO) group was explored. SNI was created by unilateral clamping and CBO was applied for 28 days. In the experiment study, motor activity, balance, and coordination measurements were made with rotarod and accelerod tests. A hot plate test was performed for analgesia measurements. Histopathology studies were carried out with the sciatic nerve tissues. RESULTS: In the rotarod test, there was a statistically significant difference between the SNI group and the SNI+CBO group (p<0.05). According to the accelerod test findings, there was a statistically significant difference between the SNI group with the Sham and SNI+CBO groups. In the hot plate test, there was a statistically significant difference between the SNI group with the Sham and SNI+CBO groups (p<0.05). In comparison to the Sham group and the SNI group, the SNI+CBO group was shown to have the greatest expression level of vimentin. CONCLUSIONS: We have concluded that CBO can be used as an adjuvant treatment in cases of SNI, increased pain, nociception, impaired balance, motor activity, and coordination. Our results will be supported by further studies.

Tuina therapy promotes behavioral improvement and brain plasticity in rats with peripheral nerve injury and repair.

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

Efficacy of Fu's Subcutaneous Needling on Sciatic Nerve Pain: Behavioral and Electrophysiological Changes in a Chronic Constriction Injury Rat Model.

Fu's subcutaneous needling (FSN), an invented acupuncture technique from traditional Chinese medicine, is used worldwide for pain relief. However, the mechanisms of action are still not fully understood. During FSN treatment, the FSN needle is inserted and retained in the subcutaneous tissues for a long duration with a swaying movement. However, challenges arise from maintaining a posture while manipulating FSN in animal models (e.g., rats) for researchers. Uncomfortable treatment can lead to fear and resistance to FSN needles, increasing the risk of injury and may even affect research data. Anesthesia may also affect the study results too. Hence, there is a need for strategies in FSN therapy on animals that minimize injury during the intervention. This study employs a chronic constriction injury model in Sprague-Dawley rats to induce neuropathic pain. This model replicates the pain induced by nerve injury observed in humans through surgical constriction of a peripheral nerve, mimicking the compression or entrapment seen in conditions such as nerve compression syndromes and peripheral neuropathies. We introduce an appropriate manipulation for easily inserting an FSN needle into the subcutaneous layer of the animal's body, including needle insertion and direction, needle retention, and swaying movement. Minimizing the rat's discomfort prevents the rat from being tense, which causes the muscle to contract and hinder the entry of the needle and improves the study efficiency.

Pulsed Electromagnetic Fields Improved Peripheral Nerve Regeneration After Delayed Repair of One Month.

The goal of this study was to determine if postoperative pulsed electromagnetic fields (PEMFs) could improve the neuromuscular rehabilitation after delayed repair of peripheral nerve injuries. Thirty-six Sprague-Dawley rats were randomly divided into sham group, control group, and PEMFs group. The sciatic nerves were transected except for the control group. One month later, the nerve ends of the former two groups were reconnected. PEMFs group of rats was subjected to PEMFs thereafter. Control group and sham group received no treatment. Four and 8 weeks later, morphological and functional changes were measured. Four and eight weeks postoperatively, compared to sham group, the sciatic functional indices (SFIs) of PEMFs group were higher. More axons regenerated distally in PEMFs group. The fiber diameters of PEMFs group were larger. However, the axon diameters and myelin thicknesses were not different between these two groups. The brain-derived neurotrophic factor and vascular endothelial growth factor expressions were higher in PEMFs group after 8 weeks. Semi-quantitative IOD analysis for the intensity of positive staining indicated that there were more BDNF, VEGF, and NF200 in PEMFs group. It's concluded that PEMFs have effect on the axonal regeneration after delayed nerve repair of one month. The upregulated expressions of BDNF and VEGF may play roles in this process. © 2023 Bioelectromagnetics Society.

Electroceuticals for Regeneration of Long Nerve Gap Using Biodegradable Conductive Conduits and Implantable Wireless Stimulator.

Regeneration of over 10 mm long peripheral nerve defects remains a challenge due to the failure of regeneration by prolonged axotomy and denervation occurring in long-term recovery. Recent studies reveal that conductive conduits and electrical stimulation accelerate the regeneration of long nerve defects. In this study, an electroceutical platform combining a fully biodegradable conductive nerve conduit and a wireless electrical stimulator is proposed to maximize the therapeutic effect on nerve regeneration. Fully biodegradable nerve conduit fabricated using molybdenum (Mo) microparticles and polycaprolactone (PCL) can eliminate the unwanted effects of non-degradable implants, which occupy nerve paths and need to be removed through surgery increasing the risk of complications. The electrical and mechanical properties of Mo/PCL conduits are optimized by controlling the amounts of Mo and tetraglycol lubricant. The dissolution behavior and electrical conductivity of biodegradable nerve conduits in the biomimetic solutions are also evaluated. In in vivo experiments, the integrated strategy of a conductive Mo/PCL conduit with controlled therapeutic electrical stimulation shows accelerated axon regeneration for long sciatic nerve defects in rats compared to the use of the Mo/PCL conduit without stimulation and has a significant therapeutic effect based on the results obtained from the functional recovery test.

Adaptive conductive electrotherapeutic scaffolds for enhanced peripheral nerve regeneration and stimulation.

BACKGROUND: While peripheral nerve stimulation (PNS) has shown promise in applications ranging from peripheral nerve regeneration to therapeutic organ stimulation, clinical implementation has been impeded by various technological limitations, including surgical placement, lead migration, and atraumatic removal. METHODS: We describe the design and validation of a platform technology for nerve regeneration and interfacing: adaptive, conductive, and electrotherapeutic scaffolds (ACESs). ACESs are comprised of an alginate/poly-acrylamide interpenetrating network hydrogel optimized for both open surgical and minimally invasive percutaneous approaches. FINDINGS: In a rodent model of sciatic nerve repair, ACESs significantly improved motor and sensory recovery (p < 0.05), increased muscle mass (p < 0.05), and increased axonogenesis (p < 0.05). Triggered dissolution of ACESs enabled atraumatic, percutaneous removal of leads at forces significantly lower than controls (p < 0.05). In a porcine model, ultrasound-guided percutaneous placement of leads with an injectable ACES near the femoral and cervical vagus nerves facilitated stimulus conduction at significantly greater lengths than saline controls (p < 0.05). CONCLUSION: Overall, ACESs facilitated lead placement, stabilization, stimulation, and atraumatic removal, enabling therapeutic PNS as demonstrated in small- and large-animal models. FUNDING: This work was supported by K. Lisa Yang Center for Bionics at MIT.