scholarly journals Vitexin alleviates neuropathic pain in a mouse chronic constriction injury model by inactivation of NF-κB

2020 ◽  
Vol 19 (5) ◽  
pp. 989-994
Author(s):  
Wentong Xu ◽  
Xueli Zhu ◽  
Gonghao Zhan ◽  
Liangyu Sheng ◽  
Yanwei Chen
Keyword(s):  
Neuropathic Pain ◽  
Inflammatory Cytokines ◽  
Chronic Constriction Injury ◽  
Enzyme Linked Immunosorbent Assay ◽  
Mrna Levels ◽  
Mechanical Hypersensitivity ◽  
Withdrawal Threshold ◽  
Before And After ◽  
Cci Model ◽  
Pro Inflammatory Cytokines

Purpose: To investigate the therapeutic effect of vitexin on neuropathic pain (NP) in a mouse model of chronic constriction injury (CCI).Methods: The CCI model was established by four chronic ligatures in the sciatic nerve. Vitexin was intraperitoneally administered (10 mg/kg, once daily) for 21 days. Mechanical withdrawal threshold (MWT) and paw withdrawal latency (PWL) were determined before and after the establishment of CCI model. The spinal cords were collected to measure mRNA levels by reverse-transcriptase polymerase chain reaction (RT-PCR) enzyme-linked immunosorbent assay (ELISA). Western blot was used to examine protein expression levels.Results: Vitexin reversed the CCI-induced reduction in MWT and PWL values, indicating that it lowered mechanical hypersensitivity response and hyperalgesia caused thermal stimulation (p < 0.05). The elevated levels of IL-6, IL-1β, and TNFα observed in CCI-treated mice were also inhibited by vitexin, suggesting that it suppressed pro-inflammatory cytokines. Moreover, vitexin attenuated CCI-induced activation of NF-κB signaling in CCI-treated mice (p < 0.05).Conclusion: Vitexin alleviates NP by inhibiting pro-inflammatory cytokines and NF-κB signaling in CCItreated mice. Thus, it is a potential target for NP treatment. Keywords: Vitexin, Neuropathic pain, Chronic constriction injury, Mechanical hypersensitivity, Hyperalgesia, NF-κB

Lidocaine activates autophagy of astrocytes and ameliorates chronic constriction injury-induced neuropathic pain

2020 ◽  
Author(s):  
Jiaqi Yuan ◽  
Yue Fei
Keyword(s):  
Cell Proliferation ◽  
Neuropathic Pain ◽  
Chronic Constriction Injury ◽  
Enzyme Linked Immunosorbent Assay ◽  
Inflammatory Factor ◽  
Experimental Basis ◽  
Withdrawal Threshold ◽  
Withdrawal Latency ◽  
Tnf Α ◽  
Rat Astrocytes

Abstract Lidocaine is a commonly used drug to alleviate neuropathic pain (NP). This work aims to investigate the mechanism of lidocaine in alleviating NP. Chronic constriction injury (CCI) rats were established by surgery to induce NP. We observed the mechanical withdrawal threshold (MWT) and thermal withdrawal latency (TWL) of rats. Immunofluorescence staining was performed to determine the LC3/glial fibrillary acidic protein (GFAP)-positive cells. Rat astrocytes were treated with lipopolysaccharide (LPS) to induce CCI, and then treated with lidocaine or 3-MA (autophagy inhibitor). CCK-8 was performed to detect cell proliferation. Western blot and enzyme-linked immunosorbent assay were performed to detect the level of protein and inflammatory factor. CCI rats exhibited a decrease of MWT and TWL, which was effectively abolished by lidocaine. Lidocaine enhanced the number of LC3/GFAP-positive cells in CCI rats. Moreover, lidocaine inhibited the expression of GFAP and p62, and enhanced LC3-II/LC3-I expression in the LPS-treated astrocytes. Lidocaine inhibited the level of TNF-α and IL-1β in the LPS-treated astrocytes. The influence conferred by lidocaine was effectively abolished by 3-MA. In conclusion, our work demonstrates that lidocaine activates autophagy of astrocytes and ameliorates CCI-induced NP. Thus, our study provides a further experimental basis for the mechanism of lidocaine to alleviate NP.

Pulsed radiofrequency to the dorsal root ganglion or the sciatic nerve reduces neuropathic pain behavior, decreases peripheral pro-inflammatory cytokines and spinal β-catenin in chronic constriction injury rats

2019 ◽  
Vol 44 (7) ◽  
pp. 742-746 ◽  
Author(s):  
Ren Jiang ◽  
Ping Li ◽  
Yong-Xing Yao ◽  
Hong Li ◽  
Rongjun Liu ◽  
...  
Keyword(s):  
Neuropathic Pain ◽  
Sciatic Nerve ◽  
Dorsal Root Ganglion ◽  
Inflammatory Cytokines ◽  
Dorsal Root ◽  
Chronic Constriction Injury ◽  
Pain Behavior ◽  
Pulsed Radiofrequency ◽  
Behavioral Tests ◽  
Pro Inflammatory Cytokines

Background and objectivesPulsed radiofrequency (PRF) is a minimal neurodestructive interventional pain therapy. However, its analgesic mechanism remains largely unclear. We aimed to investigate the peripheral and spinal mechanisms of PRF applied either adjacent to the ipsilateral L5 dorsal root ganglion (PRF-DRG) or PRF to the sciatic nerve (PRF-SN) in the neuropathic pain behavior induced by chronic constriction injury (CCI) in rats.MethodsOn day 0, CCI or sham surgeries were performed. Rats then received either PRF-DRG, PRF-SN, or sham PRF treatment on day 4. Pain behavioral tests were conducted before surgeries and on days 1, 3, 5, 7, 9, 11, 13, and 14. After the behavioral tests, the rats were sacrificed. The venous blood or sciatic nerve samples were collected for ELISAs and the dorsal horns of the L4–L6 spinal cord were collected for western blot examination.ResultsThe mechanical allodynia and the thermal hyperalgesia has been relieved by a single PRF-DRG or PRF-SN application. In addition, the analgesic effect of PRF-DRG was superior to PRF-SN on CCI-induced neuropathic pain. Either PRF-DRG or PRF-SN reversed the enhancement of interleukin 1β (IL-1β) and tumor necrosis factor alpha (TNF-α) levels in the blood of CCI rats. PRF-DRG or PRF-SN also downregulated spinal β-catenin expression.ConclusionsPRF treatment either to DRG or to sciatic nerve reduced neuropathic pain behavior, and reduced peripheral levels of pro-inflammatory cytokines and spinal β-catenin expression in CCI rats. PRF to DRG has a better analgesic effect than PRF to the nerve.

scholarly journals Pulsed Radiofrequency Improves Neuropathic Pain in Chronic Constriction Injury Rats through the Upregulation of the Transcription and Translation Levels of Glial Cell Line-Derived Neurotrophic Factor

2018 ◽  
Vol 1 (21;1) ◽  
pp. 33-40 ◽  
Author(s):  
Luo Fang
Keyword(s):  
Cell Line ◽  
Neurotrophic Factor ◽  
Chronic Constriction Injury ◽  
Pulsed Radiofrequency ◽  
Chain Reaction ◽  
Withdrawal Threshold ◽  
Before And After ◽  
Polymerase Chain ◽  
Cci Model ◽  
The Right

Background: Several studies in recent years have confirmed that the direct application of pulsed radiofrequency (PRF) on peripheral nerve compression points can alleviate hyperalgesia in animal models of neuropathic pain (NP). However, the mechanism underlying the treatment of peripheral nerves by PRF is unclear. Objectives: We aim to observe changes in pain behavior after the application of PRF on the ligation site of the sciatic nerves (SNs) of rats with chronic constriction injury (CCI) and to investigate the effects of PRF on the transcription and translation levels of glial cell line-derived neurotrophic factor (GDNF) in nerve tissues at the treatment site. Study Design: A randomized, experimental trial. Setting: Experimental Animal Center, Beijing Tiantan Hospital. Methods: Ninety-six adult male Sprague-Dawley rats were randomly divided into 4 groups: sham-sham (SS) group, sham-PRF (SP) group, CCI-sham (CS) group, and CCI-PRF (CP) group. The right SNs of rats in the CS and CP group were ligated to establish the CCI model. The right SNs in the SS and SP groups were isolated and exposed but without being ligated. On the fourteenth day after CCI/sham operation, PRF treatment was performed on the midpoint of the ligation sites of the SN in the CP group and the corresponding sites in the SP group. The electrode was only placed at the ligation sites of the SN in the CS group and the corresponding sites in the SS group without current being applied. The 50% paw withdrawal threshold (50%PWT) and thermal withdrawal latency (TWL) of rats in all of the groups were measured. The transcription and translation levels of GDNF of the PRF/sham treatment sites were measured before and after treatment by reverse transcription-polymerase chain reaction (RT-PCR) and enzyme-linked immunosorbent assays (ELISAs). Results: The 50%PWT value of the hind paws of rats in the CP group gradually increased on day 6 after the PRF treatment and was significantly higher than that in the CS group (6 days after treatment P < 0.05; 14 days after treatment P < 0.01). The TWL value in the CP group was higher than that in the CS group 2 days after treatment (P < 0.05) and was significantly higher (P < 0.01) from day 6 until the end of the experiment. On the day 6 and 14 after PRF treatment, the mRNA and protein expression levels of GDNF at the ligation sites of the SNs of rats in the CP group were higher than both the levels before treatment and those in the CS group (P < 0.01). Limitations: The efficacy of PRF treatment in the CCI model was only tested within 14 days, and the changes in GDNF levels were only tested at 3 time-points before and after treatment. Conclusions: The direct application of PRF on SN ligation sites in the CCI model can safely and effectively alleviate NP. One of the mechanisms of this effect could be the upregulation of the transcription and translation of GDNF in compressed SNs. Key words: Pulsed radiofrequency, chronic constriction injury, sciatic nerve, 50% paw withdrawal threshold, thermal withdrawal latency, glia cell line-derived neurotrophic factor, reverse transcription-polymerase chain reaction, enzyme-linked immunosorbent assay

scholarly journals Berberine reduces neuroglia activation and inflammation in streptozotocin-induced diabetic mice

2019 ◽  
Vol 33 ◽  
pp. 205873841986637 ◽  
Author(s):  
Mei Liu ◽  
Linlin Gao ◽  
Na Zhang
Keyword(s):  
Neuropathic Pain ◽  
Inflammatory Cytokines ◽  
Thermal Hyperalgesia ◽  
Enzyme Linked Immunosorbent Assay ◽  
Diabetic Mice ◽  
Mechanical Threshold ◽  
Tnf Α ◽  
Inflammatory Proteins ◽  
Necrosis Factor ◽  
Pro Inflammatory Cytokines

We aimed to analyze the action of berberine on the neuropathic pain and neuroglia activation in experimental diabetes mellitus (DM) model. Diabetes in mice was induced by intraperitoneal injection of streptozotocin (STZ) followed by the administration of berberine. Mechanical allodynia and thermal hyperalgesia and activations of microglia and astrocytes were evaluated. The levels of pro-inflammatory cytokines and protein expressions of inflammatory proteins were assessed by enzyme-linked immunosorbent assay (ELISA) and western blot, respectively. Our results revealed the anti-nociceptive effects of berberine in DM mice, supported by the improved mechanical threshold and thermal latency. In addition, berberine suppressed the activations of microglia and astrocytes in the spinal cords of diabetic mice. Berberine inhibited the expression of pro-inflammatory cytokines including tumor necrosis factor (TNF)-α, interleukin-6 (IL-6), and interleukin-1β (IL-1β), along with inflammatory proteins including iNOS and COX-2. Berberine suppressed neuropathic pain in STZ-induced diabetic mice, and this effect is related to the reduction on the neuroglia activation and inflammation associated with DM.

scholarly journals Modulation of ACE-2 mRNA by inflammatory cytokines in human thyroid cells: a pilot study

Endocrine ◽  
2021 ◽  
Author(s):  
Francesca Coperchini ◽  
Gianluca Ricci ◽  
Laura Croce ◽  
Marco Denegri ◽  
Rubina Ruggiero ◽  
...  
Keyword(s):  
Inflammatory Cytokines ◽  
Combination Treatment ◽  
Primary Cultures ◽  
Human Thyroid ◽  
Thyroid Cell ◽  
Mrna Levels ◽  
Thyroid Cells ◽  
Tnf Α ◽  
Ifn Γ ◽  
Pro Inflammatory Cytokines

Abstract Introduction Angiotensin-converting-enzyme-2 (ACE-2) was demonstrated to be the receptor for cellular entry of SARS-CoV-2. ACE-2 mRNA was identified in several human tissues and recently also in thyroid cells in vitro. Purpose Aim of the present study was to investigate the effect of pro-inflammatory cytokines on the ACE-2 mRNA levels in human thyroid cells in primary cultures. Methods Primary thyroid cell cultures were treated with IFN-γ and TNF-α alone or in combination for 24 h. ACE-2 mRNA levels were measured by RT-PCR. As a control, the levels of IFN-γ inducible chemokine (CXCL10) were measured in the respective cell culture supernatants. Results The mean levels of ACE-2 mRNA increased after treatment with IFN-γ and TNF-α in all the thyroid cell preparations, while the combination treatment did not consistently synergically increase ACE-2-mRNA. At difference, CXCL10 was consistently increased by IFN-γ and synergically further increased by the combination treatment with IFN-γ + TNF-α, with respect to IFN-γ alone. Conclusions The results of the present study show that IFN-γ and, to a lesser extent TNF-α consistently increase ACE-2 mRNA levels in NHT primary cultures. More interestingly, the combined stimulation (proven to be effective according to the synergic effect registered for CXCL10) produces different responses in terms of ACE-2 mRNA modulation. These results would suggest that elevated levels of pro-inflammatory cytokines could facilitate the entering of the virus in cells by further increasing ACE-2 expression and/or account for the different degree of severity of SARS-COV-2 infection. This hypothesis deserves to be confirmed by further specific studies.

scholarly journals AB0103 THE AMBIGUOUS ROLE OF TISSUE CYTOKINES IN THE PATHOGENESIS OF RHEUMATOID ARTHRITIS

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 1350.1-1351
Author(s):  
O. Korolik ◽  
В. Zavodovsky ◽  
E. Papichev ◽  
Y. Polyakova ◽  
S. L ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
High Activity ◽  
Inflammatory Cytokines ◽  
Stage Iii ◽  
Enzyme Linked Immunosorbent Assay ◽  
Healthy Individuals ◽  
Fetuin A ◽  
High Level ◽  
Extraarticular Manifestations ◽  
Pro Inflammatory Cytokines

Background:Cytokines stimulate the inflammatory response in the synovial membrane with rheumatoid arthritis (RA), initiate apoptosis of chondrocytes, activation of osteoclasts. The progression of comorbid diseases is also associated with the influence of cytokines. At the same time, anti-inflammatory cytokines are produced in various tissues. Their role in the pathogenesis of RA and its complications is ambiguous.Adiponectin (A) and Fetuin A (FA) are classified as negative acute phase proteins. Their concentration decreases with an increase in the level of pro-inflammatory cytokines: TNF-α, IL-1 and IL-6. Molecules A and FA, regardless of various factors and from each other, have similar effects in relation to pro-inflammatory cytokines, lipid and carbohydrate metabolism.Visfatin (V) and Nesfatin-1 (N-1) are pro-inflammatory adipokines. B is produced by cells of the mononuclear phagocytic system and connective tissue. N-1 - is produced by the cells of the intermediate and medulla oblongata and by the cells of the gastric mucosa.Objectives:to study the correlation of B, H-1, A and FA with the severity of inflammation in RAMethods:60 patients with RA and 30 healthy individuals were examined. The level of cytokines was determined by an indirect enzyme-linked immunosorbent assay using commercial test systems (Bio Vendor, cat No. RD195023100, Bio Vendor Human Fetuin-A, RaiBiotech, cat No. EIA-VIS-1, RaiBiotech, cat No. EIA-NESF). All patients underwent a full examination. Diagnosed with 2010 EULAR / ACR recommendations.Results:A decreased level of A (less than 0.8 μg/ml) was detected in 15 patients (25%), F-A (less than 653.55 μg/ml) in 16 (27%), a high level of V (more than 39 ng/ml) - in 55 (91%), N-1 (more than 37.95 ng/ml) - in 36 (60%), which is significantly more often than in healthy individuals. No significant difference in the levels of determined adipokines was found depending on the gender and body weight of patients with RA. The level of cytokines in RA is associated with high activity according to DAS 28, positivity by Anti-CCP, extraarticular manifestations of RA. The greatest correlation with extraarticular manifestations is with cutaneous and cerebral vasculitis. The levels of FA and N-1 also correlated with more pronounced radiological changes (X-ray stage III). FA circulating inhibitor of ectopic calcification. N-1 level is positively correlated with systolic blood pressure.Conclusion:A low level of A and FA, a high level of V and N-1 is characteristic of RA with the presence of high activity and positivity in the RF and Anti-CCP. An increased level of B is determined by more than 90% of patients, which indicates its high pro-inflammatory activity. The level of F and N-1 is also associated with the degree of damage to bone tissue (stage III, a lot of erosion). A positive correlation of level V and N-1, negative A and FA with the severity of inflammation in RA confirms the involvement of these proteins in the pathogenesis. A high level of A and V increases the risk of developing cardiovascular diseases and their complications, the effect of N-1 and FA is being studied. The effect of cytokines on osteoclasts and osteoblasts in RA is ambiguousReferences:[1]Visfatin and Rheumatoid Arthritis: Pathogenetic Implications and Clinical Utility. Polyakova Y. Curr Rheumatol Rev.2019[2]Serum nesfatin -1 as a marker of systemic inflammation in rheumatoid arthritis. Kvlividze T. Klinicheskaya Laboratornaya Diagnostika.2019; 64 (1):53-56 (in Russ)[3]Fetuin-A. Novel hepatokine in rheumatoid arthritis laboratory diagnostics. Papichev E. Klinicheskaya Laboratornaya Diagnostika.2018; 63 (12):756-760 (in Russ)Disclosure of Interests:None declared

scholarly journals POS1290 CYTOKINE BIOMARKERS IN COMMON LOW BACK PAIN

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 926.3-926
Author(s):  
R. Dhahri ◽  
A. Dghaies ◽  
M. Slouma ◽  
L. Metoui ◽  
I. Gharsallah ◽  
...  
Keyword(s):  
Neuropathic Pain ◽  
Low Back Pain ◽  
Back Pain ◽  
Inflammatory Cytokines ◽  
Enzyme Linked Immunosorbent Assay ◽  
Healthy Controls ◽  
Low Back ◽  
Tnf Α ◽  
Functional Scores ◽  
The Mean

Background:Common low back pain (LBP) is a common health problem affecting 50 to 80% of working age adults. It is one of the common and costly health problems in Tunisia. Actually, the role of the immune response and inflammatory cytokines in the pathogenesis of chronic pain has been of growing interest.Objectives:The aim of this study was to assess whether pro and anti-inflammatory cytokines could be detected in serum in patients with LBP compared with healthy subjects and whether they could be related to pain severity and to clinical findings.Methods:It was a an analytical cross-sectional study including 50 patients with at least three months of LBP, in the department of rheumatology, orthopedics and immunology at the Military Hospital of Tunis between January 1st and March 31, 2020. All patients had a standardized clinical assessment.Levels of serum cytokines IL-6, IL-8, IL-1β and TNF- α, were measured using the chimiluminescence technique. Serum concentration of IL-10 was assayed by the enzyme-linked immunosorbent assay technique (ELISA). The normal levels of cytokines were determined in 50 healthy controls.Results:The mean age of the patients was 41.9 ± 8.4 years and the sex ratio was 4.5. LBP duration was 66.4 months. The mean lumbar visual analog scale (VAS) was 4.5 ± 1.9, and the root VAS was 2.6 ± 2.5. Neuropathic pain was found in 26% of patients. The average BMI was 27 ± 3.7 kg/m2. Only serum level of IL-8 was significantly higher in subjects with LBP compared to healthy controls (p <10-3). IL-1β was indetectable in both patients and controls. Positive correlations were found between IL-8 levels and anxiety/functional scores (r = 0.3; p = 0.02/ r = 0.3; p = 0.04). IL-6 was positively correlated with BMI, and negatively correlated with the Schober test. No correlations were found between serum levels of IL-6, IL-8, IL-10, TNF-α and pain intensity (VAS), neuropathic pain (DN4), fibromyalgia (FIRST), depression (HAD) and various radiological data.Conclusion:Interleukin-8 is a biomarker of common low back pain and correlate with anxiety and functional disability. These results suggest that IL-8 may be a therapeutic target to reduce chronic back pain and reduce the social and profession impact.Disclosure of Interests:None declared

scholarly journals Spirulina Lipids Alleviate Oxidative Stress and Inflammation in Mice Fed a High-Fat and High-Sucrose Diet

Marine Drugs ◽  
2020 ◽  
Vol 18 (3) ◽  
pp. 148 ◽  
Author(s):  
Yuhong Yang ◽  
Lei Du ◽  
Masashi Hosokawa ◽  
Kazuo Miyashita
Keyword(s):  
Oxidative Stress ◽  
Inflammatory Cytokines ◽  
Lipid Hydroperoxide ◽  
Mrna Levels ◽  
High Fat ◽  
Inflammatory Status ◽  
Sucrose Diet ◽  
High Sucrose Diet ◽  
High Sucrose ◽  
Pro Inflammatory Cytokines

High-fat and high-sucrose diet (HFHSD)-induced obesity leads to oxidative stress and chronic inflammatory status. However, little is known about the beneficial effects of total lipids extracted from Spirulina. Hence, in the present study, Spirulina lipids were extracted with chloroform/methanol (SLC) or ethanol (SLE) and then their effects on oxidative stress and inflammation in the mice fed a HFHSD were investigated. The results show that the major lipid classes and fatty acid profiles of SLC and SLE were almost similar, but the gamma-linolenic acid (GLA) and carotenoid contents in SLE was a little higher than that in SLC. Dietary 4% SLC or SLE for 12 weeks effectively decreased the hepatic lipid hydroperoxide levels as well as increased the activities and mRNA levels of antioxidant enzymes in the mice fed a HFHSD. In addition, supplementation with SLC and SLE also markedly decreased the levels of serum pro-inflammatory cytokines and the mRNA expression of pro-inflammatory cytokines in the liver and epididymal white adipose tissue of mice fed a HFHSD, and the effects of SLC and SLE were comparable. These findings confirm for the first time that dietary Spirulina lipids could alleviate HFHSD-induced oxidative stress and inflammation.

scholarly journals Impact of loganin on pro-inflammatory cytokines and depression- and anxiety-like behaviors in male diabetic rats

2018 ◽  
Vol 105 (2) ◽  
pp. 116-126 ◽  
Author(s):  
M Rajabi ◽  
G Mohaddes ◽  
F Farajdokht ◽  
S Nayebi Rad ◽  
M Mesgari ◽  
...  
Keyword(s):  
Body Weight ◽  
Blood Glucose ◽  
Inflammatory Cytokines ◽  
Diabetic Rats ◽  
Assay Method ◽  
Enzyme Linked Immunosorbent Assay ◽  
Depression And Anxiety ◽  
Tnf Α ◽  
Immobility Time ◽  
Pro Inflammatory Cytokines

Behavioral disturbances are observed in most patients suffering from diabetes. According to some evidence, pro-inflammatory cytokines have a key role both in diabetes and behavioral disorders, such as anxiety and depression. In this study, the effect of chronic administration of loganin, as a bioflavonoid, was investigated on pro-inflammatory cytokines and depression- and anxiety-like behaviors in streptozotocin-induced diabetes in male Wistar rats. Blood levels of interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α) were assessed by enzyme-linked immunosorbent assay method. Depression- and anxiety-like behaviors were evaluated by forced swimming test (FST), elevated plus maze (EPM), and open field test (OFT), respectively. Body weight was also measured before the interventions and after the experiments in all groups. Our findings show that loganin-treated animals had significantly lower serum concentrations of IL-6 and TNF-α compared with the diabetic group. In the EPM test, loganin treatment significantly increased the percentage of the open arm time and open arm entries. Moreover, loganin treatment significantly decreased the grooming time and restored distance traveled and center crossing in the OFT. However, it decreased immobility time in the FST. Loganin treatment also significantly restored body weight gain and attenuated blood glucose changes in the diabetic rats. These results indicate that loganin possibly alleviates depression- and anxiety-like behaviors associated with diabetes through lowering the blood glucose and pro-inflammatory cytokine levels. More research is required to show the exact mechanism of antidepressant and anxiolytic effects of loganin in diabetes.

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