scholarly journals Tempol, a Superoxide Dismutase Mimetic Agent, Inhibits Superoxide Anion-Induced Inflammatory Pain in Mice

2017 ◽  
Vol 2017 ◽  
pp. 1-15 ◽  
Author(s):  
Catia C. F. Bernardy ◽  
Ana C. Zarpelon ◽  
Felipe A. Pinho-Ribeiro ◽  
Cássia Calixto-Campos ◽  
Thacyana T. Carvalho ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Superoxide Dismutase ◽  
Mrna Expression ◽  
Inflammatory Pain ◽  
Superoxide Anion ◽  
Thermal Hyperalgesia ◽  
Mechanical Hyperalgesia ◽  
Antioxidant Defenses ◽  
Paw Edema ◽  
Anti Inflammatory

The present study evaluated the anti-inflammatory and analgesic effects of the superoxide dismutase mimetic agent tempol in superoxide anion-induced pain and inflammation. Mice were treated intraperitoneally with tempol (10–100 mg/kg) 40 min before the intraplantar injection of a superoxide anion donor, potassium superoxide (KO2, 30 μg). Mechanical hyperalgesia and thermal hyperalgesia, paw edema, and mRNA expression of peripheral and spinal cord mediators involved in inflammatory pain, TNFα, IL-1β, IL-10, COX-2, preproET-1, gp91phox, Nrf2, GFAP, and Iba-1, were evaluated. Peripheral and spinal cord reductions of antioxidant defenses and superoxide anion were also assessed. Tempol reduced KO2-induced mechanical hyperalgesia and thermal hyperalgesia and paw edema. The increased mRNA expression of the evaluated mediators and oxidative stress in the paw skin and spinal cord and increased mRNA expression of glial markers in the spinal cord induced by KO2 were successfully inhibited by tempol. KO2-induced reduction in Nrf2 mRNA expression in paw skin and spinal cord was also reverted by tempol. Corroborating the effect of tempol in the KO2 model, tempol also inhibited carrageenan and CFA inflammatory hyperalgesia. The present study demonstrates that tempol inhibits superoxide anion-induced molecular and behavioral alterations, indicating that tempol deserves further preclinical studies as a promising analgesic and anti-inflammatory molecule for the treatment of inflammatory pain.

scholarly journals Dimethyl itaconate attenuates CFA-induced inflammatory pain via NLRP3/ IL-1β signaling pathway

2021 ◽  
Author(s):  
Jiaqi Lin ◽  
Jinxuan Ren ◽  
Bin Zhu ◽  
Yi Dai ◽  
Dave Schwinn Gao ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Signaling Pathway ◽  
Nlrp3 Inflammasome ◽  
Inflammatory Pain ◽  
Thermal Hyperalgesia ◽  
Inflammatory Factors ◽  
Vehicle Group ◽  
Inflammatory Factor ◽  
Anti Inflammatory ◽  
Dimethyl Itaconate

Abstract Background Itaconate plays potent anti-inflammatory effects and has gradually been discovered as a promising drug candidate for treating inflammatory diseases. However, its roles and underlying mechanism on pain remain unknown. Methods In the current work, we investigated the effects and mechanisms of dimethyl itaconate (DI, a derivative of itaconate) in a mouse model of complete Freund's adjuvant (CFA)-induced inflammatory pain. Male/Female C57 BL/6 mice were randomly divided into five groups: a vehicle group, an CFA group ,an CFA+PBS group and an CFA + DI(10mg /d and 20 mg/d) group.DI was performed for 11 consecutive days after CFA models were established.Paw withdrawal frequencies and paw withdrawal latencies were used to Behavioral Tests. The activation of macrophages and microglia, the level of proinflammatory cytokine production, the number of M1/M2 macrophages were evaluated .The possible involvement of the NLRP3/ IL-1β signaling pathway was also investigated. Results DI significantly reduced mechanical allodynia and thermal hyperalgesia, decreased peripheral inflammatory cell infiltration and the expression of pro-inflammatory factors IL-1β and TNF-α, and upregulated anti-inflammatory factor IL-10. Interestingly, DI promoted macrophages at the inflammatory site polarization from M1 into M2 type. Additionally, DI inhibited activation of macrophages in dorsal root ganglion (DRG) and microglia in the spinal cord, exhibiting reduced expressions of pro-inflammatory cytokines. Mechanismly, DI exerts the analgesic action primarily via inhibiting the activation of NLRP3 inflammasome complex and the release of IL-1β in derived and resident macrophages in the hind paw, DRG and spinal cord. Conclusion DI could alleviate the pain-like behavior of CFA mice by inhibiting the infiltration of plantar inflammatory cells and macrophages activation in DRG and microglia in the spinal cord. The analgesic behavior of itaconate was related to the inhibition of NLRP3 inflammasome. This study suggested possible evidence for prospective itaconate utilization in the management of inflammatory pain for the first time.

scholarly journals TRPV1 Blocker HCRG21 Suppresses TNF-α Production and Prevents the Development of Edema and Hypersensitivity in Carrageenan-Induced Acute Local Inflammation

Biomedicines ◽  
2021 ◽  
Vol 9 (7) ◽  
pp. 716
Author(s):  
Oksana Sintsova ◽  
Irina Gladkikh ◽  
Anna Klimovich ◽  
Yulia Palikova ◽  
Viktor Palikov ◽  
...  
Keyword(s):  
Transient Receptor Potential ◽  
Thermal Hyperalgesia ◽  
Control Group ◽  
Transient Receptor Potential Vanilloid ◽  
Paw Edema ◽  
Mice Model ◽  
Edema Formation ◽  
Sensitivity Experiment ◽  
Tnf Α ◽  
Anti Inflammatory

Currently the TRPV1 (transient receptor potential vanilloid type 1) channel is considered to be one of the main targets for pro-inflammatory mediators including TNF-α. Similarly, the inhibition of TRPV1 activity in the peripheral nervous system affects pro-inflammatory mediator production and enhances analgesia in total. In this study, the analgesic and anti-inflammatory effects of HCRG21, the first peptide blocker of TRPV1, were demonstrated in a mice model of carrageenan-induced paw edema. HCRG21 in doses of 0.1 and 1 mg/kg inhibited edema formation compared to the control, demonstrated complete edema disappearance in 24 h in a dose of 1 mg/kg, and effectively reduced the productionof TNF-α in both doses examined. ELISA analysis of blood taken 24 h after carrageenan administration showed a dramatic cytokine value decrease to 25 pg/mL by HCRG21 versus 100 pg/mL in the negative control group, which was less than the TNF-α level in the intact group (40 pg/mL). The HCRG21 demonstrated potent analgesic effects on the models of mechanical and thermal hyperalgesia in carrageenan-induced paw edema. The HCRG21 relief effect was comparable to that of indomethacin taken orally in a dose of 5 mg/kg, but was superior to this nonsteroidal anti-inflammatory drug (NSAID) in duration (which lasted 24 h) in the mechanical sensitivity experiment. The results confirm the existence of a close relationship between TRPV1 activity and TNF-α production once again, and prove the superior pharmacological potential of TRPV1 blockers and the HCRG21 peptide in particular.

scholarly journals Short-chain fatty acids contribute to neuropathic pain via regulating microglia activation and polarization

2021 ◽  
Vol 17 ◽  
pp. 174480692199652
Author(s):  
Feng Zhou ◽  
Xian Wang ◽  
Baoyu Han ◽  
Xiaohui Tang ◽  
Ru Liu ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Neuropathic Pain ◽  
Thermal Hyperalgesia ◽  
Short Chain Fatty Acids ◽  
Antibiotic Administration ◽  
Tnf Α ◽  
Microglia Polarization ◽  
Inflammatory Phenotype ◽  
Phenotype Markers ◽  
Anti Inflammatory

Microglia activation and subsequent pro-inflammatory responses play a key role in the development of neuropathic pain. The process of microglia polarization towards pro-inflammatory phenotype often occurs during neuroinflammation. Recent studies have demonstrated an active role for the gut microbiota in promoting microglial full maturation and inflammatory capabilities via the production of Short-Chain Fatty Acids (SCFAs). However, it remains unclear whether SCFAs is involved in pro-inflammatory/anti-inflammatory phenotypes microglia polarization in the neuropathic pain. In the present study, chronic constriction injury (CCI) was used to induce neuropathic pain in mice, the mechanical withdrawal threshold, thermal hyperalgesia were accomplished. The levels of microglia markers including ionized calcium-binding adaptor molecule 1 (Iba1), cluster of differentiation 11b (CD11b), pro-inflammatory phenotype markers including CD68, interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), and anti-inflammatory phenotype markers including CD206, IL-4 in the hippocampus and spinal cord were determined on day 21 after CCI. The results showed that CCI produced mechanical allodynia and thermal hyperalgesia, and also increased the expressions of microglia markers (Iba1, CD11b) and pro-inflammatory phenotype markers (CD68, IL-1β, and TNF-α), but not anti-inflammatory phenotype marker (CD206, IL-4) in the hippocampus and spinal cord, accompanied by increased SCFAs in the gut. Notably, antibiotic administration reversed these abnormalities, and its effects was also bloked by SCFAs administration. In conclusion, data from our study suggest that CCI can lead to mechanical and thermal hyperalgesia, while SCFAs play a key role in the pathogenesis of neuropathic pain by regulating microglial activation and subsequent pro-inflammatory phenotype polarization. Antibiotic administration may be a new treatment for neuropathic pain by reducing the production of SCFAs and further inhibiting the process of microglia polarization.

scholarly journals Electroacupuncture Inhibits Spinal Interleukin-17A to Alleviate Inflammatory Pain in a Rat Model

2013 ◽  
Vol 6 (1) ◽  
pp. 183-189 ◽  
Author(s):  
Xianze Meng ◽  
Lixing Lao ◽  
Xue-Yong Shen ◽  
Brian M. Berman ◽  
Ke Ren ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Inflammatory Pain ◽  
Thermal Hyperalgesia ◽  
Lumbar Spinal Cord ◽  
Thermal Stimulus ◽  
Sham Control ◽  
Interleukin 17A ◽  
Neuronal Interactions ◽  
Lumbar Spinal ◽  
Essential Subunit

Although acupuncture analgesia has been reported in clinical trials, its mechanisms have been unclear. It was recently reported that spinal astrocytes-produced interleukin-17A (IL-17A) facilitates inflammatory pain. Hypothesizing that electroacupuncture (EA) would suppress inflammation-enhanced IL-17A synthesis to inhibit pain, we induced hyperalgesia, as measured by decreased paw withdrawal latency (PWL) to a noxious thermal stimulus, by subcutaneously injecting complete Freund's adjuvant (CFA, 0.08 ml, 40 μg Mycobacterium tuberculosis) into the hind paws of rats, or intrathecal (i.t.) IL-17A (400 ng in 10 μl) into the lumbar spinal cord. We then gave EA at acupoint GB30 for two 20-min periods, once immediately after CFA or IL-17A administration and again 2 h post-injection. For sham control, EA needles were inserted into GB30 without stimulation. PWL was measured before and 2.5 and 24 h after injection. Spinal IL-17A, IL-17 receptor A (IL-17RA), and phosphorylated NR1, an essential subunit of the N-methyl D-aspartate receptor (NMDAR), were determined 24 h post-CFA or –IL-17A using immunohistochemistry and western blot. Compared to sham control, EA inhibited CFA-caused thermal hyperalgesia 2.5 and 24 h post-CFA and concurrently suppressed inflammation-enhanced IL-17A and IL-17RA synthesis and NR1 phosphorylation in the ipsilateral spinal cord. EA inhibited IL-17A-produced thermal hyperalgesia, IL-17RA synthesis and NR1 phosphorylation. Our data suggest that EA inhibits inflammatory pain by blocking spinal IL-17A synthesis. Since previous study shows that IL-17A is located in astrocytes and IL-17RA and NR1 are in neurons, the data suggest that EA alleviates pain by modulating glia-neuronal interactions that involve IL-17A, IL-17RA, and NR1 phosphorylation.

scholarly journals Reciprocal Regulatory Interaction between TRPV1 and Kinin B1 Receptor in a Rat Neuropathic Pain Model

2020 ◽  
Vol 21 (3) ◽  
pp. 821 ◽  
Author(s):  
Veronica Cernit ◽  
Jacques Sénécal ◽  
Rahmeh Othman ◽  
Réjean Couture
Keyword(s):  
Spinal Cord ◽  
Neuropathic Pain ◽  
Mrna Expression ◽  
Thermal Hyperalgesia ◽  
Mrna Levels ◽  
Regulatory Interaction ◽  
B1 Receptor ◽  
Tnf Α ◽  
Kinin B1 Receptor ◽  
Sensory Fibers

Kinins are mediators of pain and inflammation and evidence suggests that the inducible kinin B1 receptor (B1R) is involved in neuropathic pain (NP). This study investigates whether B1R and TRPV1 are colocalized on nociceptors and/or astrocytes to enable regulatory interaction either directly or through the cytokine pathway (IL-1β, TNF-α) in NP. Sprague Dawley rats were subjected to unilateral partial sciatic nerve ligation (PSNL) and treated from 14 to 21 days post-PSNL with antagonists of B1R (SSR240612, 10 mg·kg−1, i.p.) or TRPV1 (SB366791, 1 mg·kg−1, i.p.). The impact of these treatments was assessed on nociceptive behavior and mRNA expression of B1R, TRPV1, TNF-α, and IL-1β. Localization on primary sensory fibers, astrocytes, and microglia was determined by immunofluorescence in the lumbar spinal cord and dorsal root ganglion (DRG). Both antagonists suppressed PSNL-induced thermal hyperalgesia, but only SB366791 blunted mechanical and cold allodynia. SSR240612 reversed PSNL-induced enhanced protein and mRNA expression of B1R and TRPV1 mRNA levels in spinal cord while SB366791 further increased B1R mRNA/protein expression. B1R and TRPV1 were found in non-peptide sensory fibers and astrocytes, and colocalized in the spinal dorsal horn and DRG, notably with IL-1β on astrocytes. IL-1β mRNA further increased under B1R or TRPV1 antagonism. Data suggest that B1R and TRPV1 contribute to thermal hyperalgesia and play a distinctive role in allodynia associated with NP. Close interaction and reciprocal regulatory mechanism are suggested between B1R and TRPV1 on astrocytes and nociceptors in NP.

Antihypernociceptive and antioxidant effects of Petersianthus macrocarpus stem bark extracts in rats with complete Freund’s adjuvant-induced persistent inflammatory pain

2017 ◽  
Vol 14 (2) ◽  
Author(s):  
Francis Desire Tatsinkou Bomba ◽  
Bibiane Aimée Wandji ◽  
Christian Kuete Fofié ◽  
Albert Kamanyi ◽  
Télesphore Benoit Nguelefack
Keyword(s):  
Spinal Cord ◽  
Inflammatory Pain ◽  
Folk Medicine ◽  
Antioxidant Properties ◽  
Stem Bark ◽  
Oral Route ◽  
Mechanical Hyperalgesia ◽  
Intraplantar Injection ◽  
Field Device ◽  
The Brain

AbstractBackground(P. Beauv.) Liben (Lecythidaceae) is a plant used in Cameroonian folk medicine to cure ailments such as inflammation and pain. Previous work showed that aqueous (AEPM) and methanol (MEPM) extracts from the stem bark ofMethodsInflammatory pain was induced by intraplantar injection of CFA into the left hind paw of Wistar rats. AEPM and MEPM were administered either acutely or chronically by the oral route at the doses of 100 and 200 mg/kg/day. The mechanical hyperalgesia was tested using an analgesimeter, while the locomotion activity at the end of experiment was evaluated with an open-field device. Nitric oxide (NO), malondialdehyde (MDA) and superoxide dismutase (SOD) contents were assayed in the brain and spinal cord of rats subjected to 14 days chronic treatment.ResultsAEPM and MEPM at both doses significantly (p<0.001) inhibited the acute and chronic mechanical hyperalgesia induced by CFA. Although not significant, both extracts increased the mobility of CFA-injected animals. AEPM significantly (p<0.01) reduced the level of nitrate at 100 mg/kg, MDA at 200 mg/kg and significantly (p<0.05) increased the SOD in the spinal cord. MEPM significantly increased the SOD content and reduced the MDA concentration in the brain but had no effect on the nitrate.ConclusionsAEPM and MEPM exhibit acute and chronic antihyperalgesic activities. In addition, both extracts possess antioxidant properties that might strengthen their chronic antihyperalgesic effects.

scholarly journals Protective Effect ofFlos Loniceraeagainst Experimental Gastric Ulcers in Rats: Mechanisms of Antioxidant and Anti-Inflammatory Action

2014 ◽  
Vol 2014 ◽  
pp. 1-11 ◽  
Author(s):  
Jung-Woo Kang ◽  
Nari Yun ◽  
Hae-Jung Han ◽  
Jeom-Yong Kim ◽  
Joo-Young Kim ◽  
...  
Keyword(s):  
Lipid Peroxidation ◽  
Superoxide Dismutase ◽  
Acetic Acid ◽  
Gastric Ulcer ◽  
Mrna Expression ◽  
Inflammatory Cytokines ◽  
Gastric Wall ◽  
Myeloperoxidase Activity ◽  
Flos Lonicerae ◽  
Anti Inflammatory

Flos Loniceraeis one of the oldest and most commonly prescribed herbs in Eastern traditional medicine to treat various inflammatory diseases. In the present study, we investigated the effects of ethyl acetate fraction ofFlos Lonicerae(GC-7101) on experimental gastric ulcer models and its mechanisms of action in gastric ulcer healing. The pharmacological activity of GC-7101 was investigated in rats on HCl/EtOH, indomethacin, water immersion restraint stress induced acute gastric ulcer, and acetic-acid-induced subchronic gastric ulcer. To determine its gastroprotective mechanisms, gastric wall mucus secretion, mucosal PGE2, mucosal NO content, nuclear translocation of NF-κB, mRNA expression of inflammatory cytokines, lipid peroxidation and glutathione content, and superoxide dismutase and catalase activities were measured. GC-7101 significantly attenuated development of acute gastric ulcer and accelerated the healing of acetic-acid-induced subchronic gastric ulcer. In HCl/EtOH-induced gastric ulcer, GC-7101 markedly enhanced gastric wall mucus content which was accompanied by increased mucosal PGE2and NO production. Furthermore, treatment of GC-7101 exhibited anti-inflammatory and antioxidant activities as evidenced by decreased myeloperoxidase activity, NF-κB translocation, inflammatory cytokines mRNA expression, and lipid peroxidation and increased glutathione content and superoxide dismutase and catalase activities. These results demonstrated that GC-7101 possesses strong antiulcerogenic effect by modulating oxidative stress and proinflammatory mediators.

scholarly journals Hydroethanolic Extract of Grape Peel from Vitis labrusca Winemaking Waste: Antinociceptive and Anti-Inflammatory Activities

2021 ◽  
Vol 60 (1) ◽  
Author(s):  
Cristiana F. G. Silva ◽  
Victor Fattori ◽  
Caroline R. Tonetti ◽  
Marcos A. S. Ribeiro ◽  
Ricardo L. N. Matos ◽  
...  
Keyword(s):  
Phenolic Compounds ◽  
Biological Effects ◽  
Multiple Reaction Monitoring ◽  
Thermal Hyperalgesia ◽  
Neutrophil Recruitment ◽  
Grape Pomace ◽  
Paw Edema ◽  
Vitis Labrusca ◽  
Anti Inflammatory ◽  
Hydroethanolic Extract

Research background. Extracts from grape pomace, including the wine, showed many biological effects such as antioxidant and anti-inflammatory activities. Unfortunately winemakers discard the bagasse and the waste is less useful, however it contains bioactive compounds which result in antioxidant and anti-inflammatory properties. The work aimed to analyze the hydroethanolic extract of peels from agro-industrial waste from Vitis labrusca and to evaluate its antinociceptive and anti-inflammatory assays. This study is relevant for reusing a residue and adding value to the grape economic chain. Experimental approach. A representative sample of pomace was obtained and the peels were applied to produce the extract. The phenolic compounds were determined by multiple reaction monitoring mode of mass spectrometry methods and Folin-Ciocalteu, using gallic acid as standard. The biological analyzes were carried out using mice orally treated with crude extract at doses (30, 100, and 300 mg/kg). We evaluated mechanical hyperalgesia by the von Frey method, thermal heat hyperalgesia using a hot plate at 55 °C, paw edema using a pachymeter, and neutrophil recruitment by measurement of myeloperoxidase enzyme activity. The nephrotoxicity and hepatotoxicity were evaluated by biochemical analyses using blood samples that were collected after the Vitis labrusca administration. Results and conclusions. The peels correspond to 75 % of all wet winemaking residue and 59 % on a dry basis. We identified nine anthocyanins (3-O-glucoside: peonidin, delphinidin, petunidin, and malvidin; 3-p-coumaroyl-glucoside: cyanidin, peonidin, petunidin, and malvidin, and malvidin-3,5-diglucoside), five flavonoids (apigenin-7-glucoside, luteolin-7-glucoside, quercetin-3-galactoside, isorhamnetin-3-glucoside, and myricetin-3-rutinoside), and 26.62 mg GAE/g of phenolic compounds. In vivo assays, showed that Vitis labrusca extract at concentrations 100 and 300 mg/kg reduced carrageenan-induced mechanical and thermal hyperalgesia, 50 % of the paw edema, and neutrophil recruitment. In addition, there were no nephrotoxicity and hepatotoxicity. Our extract obtained from winemaking residue has analgesic and anti-inflammatory action, related at least in part to the presence of phenolic compounds, and it has no toxicity to renal and hepatic tissues. Novelty and scientific contribution. We demonstrated that this waste can be used for the production of antioxidant and anti-inflammatory products (pharmaceutical and cosmetics) without toxicity, contributing to the environmental economy.

Antinociceptive, anti-inflammatory and antioxidant effects of Boerhavia coccinea extracts and fractions on acute and persistent inflammatory pain models

2020 ◽  
Vol 0 (0) ◽  
Author(s):  
Basile Nganmegne Piegang ◽  
Fabrice Sterlin Tchantchou Ndjateu ◽  
Mathieu Tene ◽  
Francis Désiré Tatsinkou Bomba ◽  
Pius Pum Tseuguem ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Inflammatory Pain ◽  
Chronic Treatment ◽  
Antinociceptive Effect ◽  
Repeated Administration ◽  
No Production ◽  
Herbaceous Plant ◽  
Intraplantar Injection ◽  
Anti Inflammatory ◽  
Antioxidant Effects

AbstractBackgroundBoerhavia coccinea (Nyctaginaceae) is an herbaceous plant used for the treatment of pain. The aim of this study was to evaluate the antinociceptive and anti-inflammatory activities of the aqueous (AEBC) and ethanol (EEBC) extracts of Boerhavia coccinea as well as the major fractions (F1, F2 and F3) from EEBC.MethodsThe antinociceptive effect of the extracts and fractions was evaluated using formalin test. AEBC, EEBC and F1 were selected and further evaluated acutely (24 h) and chronically (16 days) in Complete Freund’s Adjuvant (CFA)-induced persistent inflammatory pain for their antihyperalgesic and anti-inflammatory effects. They were administered orally (100 and 200 mg/kg/day) from 48 h following the intraplantar injection of 100 µL of CFA. After the 16 days of chronic treatment, rats’ spinal cord and brain were collected for the evaluation of oxidative stress parameters namely nitric oxide (NO), malondialdehyde (MDA), superoxide dismutase (SOD) and catalase (CAT).ResultsAEBC, EEBC and F1 significantly inhibited the first and second phases of the formalin-induced pain. They significantly reduced the hyperalgesia both in acute and chronic treatments. These extracts showed no acute anti-inflammatory effect. AEBC and EEBC exhibited anti-inflammatory activities after repeated administration. AEBC, EEBC and F1 significantly reduced MDA level and significantly increased SOD and catalase activities, mainly in the spinal cord. AEBC and EEBC also reduced the NO production in the spinal cord.ConclusionsBoerhavia coccinea extracts and F1 possess potent antinociceptive activity which is not related to their anti-inflammatory properties. Their antioxidant effects may contribute to these activities in chronic treatment.

Sign in / Sign up

Export Citation Format

Share Document