scholarly journals Kaempferol Attenuates the Development of Diabetic Neuropathic Pain in Mice: Possible Anti-Inflammatory and Anti-Oxidant Mechanisms

2014 ◽  
Vol 2 (3) ◽  
pp. 424-430 ◽  
Author(s):  
Osama M. Abo-Salem
Keyword(s):  
Neuropathic Pain ◽  
Body Weight Gain ◽  
Thermal Hyperalgesia ◽  
Pain Sensation ◽  
Diabetic Neuropathic Pain ◽  
Reduced Body ◽  
Markers Of Inflammation ◽  
Tnf Α ◽  
Anti Oxidant ◽  
Factor Α

BACKGROUND: Diabetic neuropathic pain (DNP) is one of the most difficult types of pain to treat.  Many studies emphasized on the role of microglial cells, oxidative stress (OS) and inflammatory cytokines (IC) in the development of diabetic neuropathy (DN).AIM: Present study was designed to evaluate the effect of kaempferol in attenuation of DN in mice. METHODS: Diabetes was induced in mice by i.p. injection of a single dose of streptozotocin (STZ) (200 mg/kg). Cold allodynia, thermal hyperalgesia and chemical hyperalgesia were assessed, as well as markers of inflammation and OS.RESULTS: Diabetic mice (DM) showed an increased pain sensation, IC and OS accompanied with reduced body weigh gain. Treatment of DM with kaempferol (25, 50 and 100 mg/kg/day/orally) attenuated the development of DN and reduced pain sensation. Moreover, it reduced interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), lipid peroxidation and nitrite, concomitant with the improvement of antioxidant defense and body weight gain. In contrast, kaempferol (100 mg/kg) had no effects on the behavioral and biochemical parameters. Our results strongly suggest that activated microglia, IC and OS are involved in the development of DN.CONCLUSIONS: Kaempferol attenuates the development of DNP in mice probably by inhibition of neuroimmune activation of microglia and, partly mediated by reducing IC and OS.

Curcumin Ameliorates Paclitaxel-Induced Pain Hypersensitivity via Alleviation of Inflammation and Oxidative Stress in Rats

2021 ◽  
Vol 11 (4) ◽  
Author(s):  
Pasupulati Haritha ◽  
SV Padi Satyanarayana ◽  
Koganti Bharathi ◽  
Koganti Prasad VSRG
Keyword(s):  
Spinal Cord ◽  
Neuropathic Pain ◽  
Peripheral Neuropathy ◽  
Mechanical Allodynia ◽  
Nitrosative Stress ◽  
Therapeutic Potential ◽  
Thermal Hyperalgesia ◽  
Antioxidant Defenses ◽  
Markers Of Inflammation ◽  
Factor Α

Painful peripheral neuropathy is the main dose-limiting and long lasting side-effect of paclitaxel therapy. Despite enormous research, there is no effective treatment for paclitaxel-induced peripheral neuropathic pain owing to poor understanding of pathophysiological mechanisms. Growing evidence indicates oxidative-nitrosative stress is one of the leading factors causing chemotherapy induced peripheral neuropathy. Recently, involvement of neuroinflammation has been suggested in the development of paclitaxel-induced neuropathic pain. It is postulated that abrogating cytokine release and improving antioxidant defenses might be suitable targets in controlling neuroinflammation and oxidative-nitrosative stress mediated nociceptive hypersensitivities. Therefore, the study evaluated the effect of curcumin on paclitaxel-induced neuropathic pain in rats. Peripheral neuropathy was induced by administration of paclitaxel (2 mg/kg per injection) intraperitoneally on four alternate days (days 0, 2, 4, 6). Thermal hyperalgesia and mechanical allodynia were assessed and the markers of inflammation and oxidative-nitrosative stress were estimated. Administration of curcumin (50 and 100 mg/kg, p.o.) for 2 weeks started 14 days after paclitaxel injection significantly alleviated paclitaxel-induced nociceptive behavioural hypersensitivity observed as reduced thermal hyperalgesia and mechanical allodynia. These observed ameliorative effects of curcumin on paclitaxel-induced neuropathic pain are accompanied by reduction of tumour necrosis factor-α, a pro-inflammatory cytokine, in both spinal cord and dorsal root ganglia and oxidative-nitrosative stress in spinal cord. The results of the present study demonstrated antihyperalgesic and antiallodynic effects of curcumin. Additional clinical studies are warranted to evaluate therapeutic potential of curcumin as antinociceptive agent in the treatment of paclitaxel-induced neuropathic pain.

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 Hypersensitivity of Spinothalamic Tract Neurons Associated With Diabetic Neuropathic Pain in Rats

2002 ◽  
Vol 87 (6) ◽  
pp. 2726-2733 ◽  
Author(s):  
Shao-Rui Chen ◽  
Hui-Lin Pan
Keyword(s):  
Neuropathic Pain ◽  
Dorsal Horn ◽  
Spinal Dorsal Horn ◽  
Thermal Hyperalgesia ◽  
Diabetic Rats ◽  
Projection Neurons ◽  
Diabetic Neuropathic Pain ◽  
Spinothalamic Tract ◽  
Functional Changes ◽  
Spinal Dorsal

Diabetic neuropathic pain is often considered to be caused by peripheral neuropathy. The involvement of the CNS in this pathological condition has not been well documented. Development of hypersensitivity of spinal dorsal horn neurons is involved in neuropathic pain induced by traumatic nerve injury. In the present study, we determined the functional changes of identified spinothalamic tract (STT) neurons and their correlation to diabetic neuropathic pain. Diabetes was induced in rats by intraperitoneal injection of streptozotocin. Hyperalgesia and allodynia were assessed by the withdrawal responses to pressure, radiant heat, and von Frey filaments applied to the hindpaw. Single-unit activity of STT neurons was recorded from the lumbar spinal cord in anesthetized rats. The responses of STT neurons to mechanical and thermal stimuli and the sensitivity to intravenous morphine were determined in diabetic and normal rats. In 12 diabetic rats, mechanical allodynia and hyperalgesia, but not thermal hyperalgesia, developed within 2 wk after streptozotocin injection and lasted for ≥7 wk. Compared to the 32 STT neurons recorded in normal animals, the 37 STT neurons in diabetic rats displayed a higher spontaneous discharge activity and enlarged receptive fields. Also, the STT neurons in diabetic rats exhibited lower thresholds and augmented responses to mechanical stimulation. Intravenous injection of 2.5 mg/kg of morphine suppressed significantly the responses of STT neurons to noxious stimuli in 12 nondiabetic rats. However, such an inhibitory effect of morphine on the evoked response of STT neurons was diminished in 14 diabetic animals. This electrophysiological study provides new information that development of hypersensitivity of spinal dorsal horn projection neurons may be closely related to neuropathic pain symptoms caused by diabetes. Furthermore, the attenuated inhibitory effects of morphine on evoked responses of STT neurons in diabetes likely accounts for its reduced analgesic efficacy in this clinical form of neuropathic pain.

Association between circulating inflammatory markers and marksmanship following intense military training

2018 ◽  
Vol 165 (6) ◽  
pp. 391-394
Author(s):  
Yftach Gepner ◽  
J R Hoffman ◽  
M W Hoffman ◽  
H Zelicha ◽  
H Cohen ◽  
...  
Keyword(s):  
Cognitive Function ◽  
Test Performance ◽  
Military Training ◽  
Protein Markers ◽  
Military Operations ◽  
Field Training ◽  
Markers Of Inflammation ◽  
Tnf Α ◽  
Combat Unit ◽  
Factor Α

IntroductionIntense military operations during deployment or training are associated with elevations in inflammatory cytokine markers. However, the influence of an inflammatory response on military-specific skills is unclear. This study examined the association between brain-derived neurotrophic factor (BDNF), glial fibrillar acidic protein, markers of inflammation, marksmanship and cognitive function following a week of intense military field training.MethodsTwenty male soldiers (20.1±0.6 years; 1.78±0.05m; 74.1±7.9kg) from the same elite combat unit of the Israel Defense Forces volunteered to participate in this study. Soldiers completed a five-day period of intense field training including navigation of 27.8km/day with load carriages of ~50% of their body mass. Soldiers slept approximately fivehours per day and were provided with military field rations. Following the final navigational exercise, soldiers returned to their base and provided a blood sample. In addition, cognitive function assessment and both dynamic and static shooting (15 shots each) were performed following a 200 m gauntlet, in which soldiers had to use hand-to-hand combat skills to reach the shooting range.ResultsResults revealed that tumour necrosis factor-α (TNF-α) concentrations were inversely correlated with dynamic shooting (r=−0.646, p=0.005). In addition, a trend (r=0.415, p=0.098) was noted between TNF-α concentrations and target engagement speed (ie, time to complete the shooting protocol). BDNF concentrations were significantly correlated with the Serial Sevens Test performance (r=0.672, p=0.012).ConclusionThe results of this investigation indicate that elevated TNF-α concentrations and lower BDNF concentrations in soldiers following intense military training were associated with decreases in marksmanship and cognitive function, respectively.

scholarly journals Loss of SNHG4 Attenuated Spinal Nerve Ligation-Triggered Neuropathic Pain through Sponging miR-423-5p

2020 ◽  
Vol 2020 ◽  
pp. 1-9 ◽  
Author(s):  
Xia Pan ◽  
Cheng Shen ◽  
Yayi Huang ◽  
Long Wang ◽  
Zhongyuan Xia ◽  
...  
Keyword(s):  
Neuropathic Pain ◽  
Molecular Mechanisms ◽  
Thermal Hyperalgesia ◽  
Spinal Nerve ◽  
Spinal Nerve Ligation ◽  
Rat Models ◽  
Tnf Α ◽  
Cord Injury ◽  
Gene 4 ◽  
Nucleolar Rna

Neuropathic pain is an intractable comorbidity of spinal cord injury. Increasing noncoding RNAs have been implicated in neuropathic pain development. lncRNAs have been recognized as significant regulators of neuropathic pain. lncRNA Small Nucleolar RNA Host Gene 4 (SNHG4) is associated with several tumors. However, the molecular mechanisms of SNHG4 in neuropathic pain remain barely documented. Here, we evaluated the function of SNHG4 in spinal nerve ligation (SNL) rat models. We observed that SNHG4 was significantly upregulated in SNL rat. Knockdown of SNHG4 was able to attenuate neuropathic pain progression via regulating behaviors of neuropathic pain including mechanical and thermal hyperalgesia. Moreover, knockdown of SNHG4 could repress the neuroinflammation via inhibiting IL-6, IL-12, and TNF-α while inducing IL-10 levels. Additionally, miR-423-5p was predicted as the target of SNHG4 by employing bioinformatics analysis. miR-423-5p has been reported to exert significantly poorer in several diseases. However, the role of miR-423-5p in the development of neuropathic pain is needed to be clarified. Here, in our investigation, RIP assay confirmed the correlation between miR-423-5p and SNHG4. Meanwhile, we found that miR-423-5p was significantly decreased in SNL rat models. SNHG4 regulated miR-423-5p expression negatively. As exhibited, the loss of miR-423-5p contributed to neuropathic pain progression, which was rescued by the silence of SNHG4. Therefore, our study indicated SNHG4 as a novel therapeutic target for neuropathic pain via sponging miR-423-5p.

scholarly journals Flow-Mediated Vasodilation Is Not Attenuated in Hypertensive Pregnancies Despite Biochemical Signs of Inflammation

2012 ◽  
Vol 2012 ◽  
pp. 1-6 ◽  
Author(s):  
Heli Saarelainen ◽  
Henna Kärkkäinen ◽  
Pirjo Valtonen ◽  
Kari Punnonen ◽  
Tomi Laitinen ◽  
...  
Keyword(s):  
Endothelial Function ◽  
Brachial Artery ◽  
Normal Pregnancy ◽  
Hypertensive Disorder ◽  
Reactive Protein ◽  
Markers Of Inflammation ◽  
Tnf Α ◽  
Factor Α ◽  
Artery Flow ◽  
Flow Mediated Vasodilation

Background. Our objective was to evaluate endothelial function and markers of inflammation during and after pregnancy in normal pregnancies compared to pregnancies complicated with hypertension or preeclampsia (PE). Methods and Results. We measured endothelium-dependent brachial artery flow-mediated vasodilation (FMD) and high sensitive C-reactive protein (hsCRP), interleukin-6 (IL-6), and tumour necrosis factor-α (TNF-α) in 32 women with normal pregnancy and in 28 women whose pregnancy was complicated with hypertensive disorder in the second half of pregnancy and minimum 3-month postpartum. Enhancement of endothelial function was greater in hypertensive than normal pregnancies, the mean FMD% being 11.0% versus 8.8% during pregnancy (P=0.194) and 8.0% versus 7.9% postpartum (P=0.978). Concentrations of markers of inflammation were markedly increased in pregnant hypertensive group compared to those after delivery (hsCRP 4.5 versus 0.80 mg/L, P=0.023, IL-6 2.1 versus 1.2 pg/mL, P=0.006; TNF-α 1.9 versus 1.5 pg/mL, P=0.030). There were no statistically significant associations between the markers of inflammation and FMD. Conclusions. Brachial artery FMD was not attenuated in the third trimester hypertensive pregnancies compared to normal pregnancies, whereas circulating concentrations of hsCRP and IL-6 and TNF-α reacted to hypertensive complications.

scholarly journals Nuclear PPAR-γ Activation Modulates Inflammation and Oxidative Stress in Attenuating Chemotherapy-Induced Neuropathic Pain in Vivo

2021 ◽  
pp. 167-179
Author(s):  
Haritha Pasupulati ◽  
Satyanarayana S. V. Padi ◽  
Sujatha Dodoala ◽  
Prasad V. S. R. G. Koganti
Keyword(s):  
Oxidative Stress ◽  
Spinal Cord ◽  
Neuropathic Pain ◽  
Peripheral Neuropathy ◽  
Mechanical Allodynia ◽  
Antinociceptive Effect ◽  
Thermal Hyperalgesia ◽  
Ppar Γ ◽  
Markers Of Inflammation ◽  
And Oxidative Stress

Background: Paclitaxel-induced painful neuropathy is a major dose-limiting side effect and can persist for up to two years after completing treatment that greatly affects both the course of chemotherapy and quality of life in cancer patients. Peroxisome proliferator-activated receptor (PPAR)-γ belongs to a family of nuclear receptors known for their transcriptional and regulatory roles in metabolism, inflammation, and oxidative stress. However, the role of PPAR-γ activation on paclitaxel-induced neuropathic pain is not yet known. Objective: To investigate whether pioglitazone, a PPAR-γ agonist reduce paclitaxel-induced neuropathic pain and to elucidate underlying mechanisms. Methodology: Peripheral neuropathy was induced by administration of paclitaxel (2 mg/kg per injection) intraperitoneally on four alternate days (days 0, 2, 4, 6). Thermal hyperalgesia and mechanical allodynia were assessed and the markers of inflammation and nitroso-oxidative stress were estimated. Results: Pioglitazone did not induce hypoalgesia and had no effect on locomotor activity. Repeated oral administration of pioglitazone (10 and 20 mg/kg,) for 2 weeks started 14 days after paclitaxel injection markedly attenuated paw withdrawal responses to thermal (hyperalgesia) and mechanical (allodynia) stimuli. Further, pioglitazone administration significantly reduced elevated level of pro-inflammatory cytokine, TNF-α, in both the dorsal root ganglia and the spinal cord accompanied by marked decrease in oxidative stress parameters as well as increase in activity of antioxidant defense enzyme, superoxide dismutase, in the spinal cord after paclitaxel injection. Conclusion: The results of the present study demonstrate that pioglitazone, a PPAR-γ agonist exerted antinociceptive effect in paclitaxel-induced neuropathic pain through inhibiting neuroimmune inflammation in both the periphery and spinal cord and by reducing nitroso-oxidative stress in spinal cord. Our findings strongly suggest pharmacological activation of PPAR-g as a promising therapeutic target in paclitaxel-induced peripheral neuropathy and provide rationale for the clinical evaluation.

scholarly journals Protocatechuic acid as an inhibitor of the JNK/CXCL1/CXCR2 pathway relieves neuropathic pain in CCI rats

2021 ◽  
Author(s):  
Hong-xia Chang ◽  
Yue-feng Zhao
Keyword(s):  
Neuropathic Pain ◽  
Sciatic Nerve ◽  
Satellite Cells ◽  
Protocatechuic Acid ◽  
Thermal Hyperalgesia ◽  
Tnf Α ◽  
Chemokine Ligand ◽  
New Perspective

Emerging evidence has shown that protocatechuic acid (PCA) has antioxidant and anti-inflammatory effects. Evidence suggests that PCA can alleviate the injury of sciatic nerve, while the mechanism of its therapeutic effect on neuralgia remains unknown.         Chromium bowel ligation was used in vivo to establish a chronic constriction injury (CCI) rat model to induce sciatic nerve pain. Subsequently, two doses of PCA were used to treat CCI rats. In vitro, 10 ng/mL TNF-α was used to stimulate glial satellite cells derived from the dorsal root ganglia (DRG) L4-L6 of the sciatic nerve to simulate sciatic nerve pain. PCA relieved mechanical allodynia and thermal hyperalgesia in CCI rats. CCK-8 assay revealed that PCA inhibited the proliferation of glial satellite cells induced by TNF-α. Moreover, ELISA demonstrated that PCA could improve the inflammatory response of rats caused by CCI and cells induced by TNF-α. Next, RT-qPCR and Western blot assays showed that PCA blocked the c-Jun N-terminal kinase/the chemokine ligand 1/CXC chemokine receptor 2 (JNK/CXCL1/CXCR2) pathway by inhibiting CXCL1 levels in cells induced by TNF-α and DRG in CCI rats. In conclusion, PCA can alleviate neuropathic pain in CCI rats and improve oxidative stress by inhibiting the JNK/CXCL1/CXCR2 signaling pathway. Thus, these findings provide a new perspective for the treatment of neuropathic pain caused by CCI.

scholarly journals Propofol Alleviates Neuropathic Pain in CCI Rat Model via the miR-140-3p/JAG1/Notch Signaling Pathway

2021 ◽  
Author(s):  
Fang Cheng ◽  
Wei Qin ◽  
Ai-xing Yang ◽  
Feng-feng Yan ◽  
Yu chen ◽  
...  
Keyword(s):  
Neuropathic Pain ◽  
Notch Signaling ◽  
Signaling Pathway ◽  
Notch Pathway ◽  
Thermal Hyperalgesia ◽  
Underlying Mechanism ◽  
Notch Signaling Pathway ◽  
Mechanical Threshold ◽  
Tnf Α ◽  
Related Proteins

Abstract As a renowned anesthetic, propofol exerts excellent analgesic function in nerve injury. However, the underlying mechanism of propofol on neuropathic pain (NP) remains unknown. The research aims to analyze propofol’s analgesia mechanism to alleviate NP in CCI rats. The chronic constriction injury (CCI) of sciatic nerve was used to established NP rat models. CCI rats were treated with propofol and its paw withdrawal mechanical threshold (PMWT) and paw withdraw thermal latency (PWTL) were measured. The expressions of TNF-α, IL-1β and IL-10 were detected. CCI rats with propofol treatment were injected with antagomiR-140-3p. After the targeting relationship between miR-140-3p and JAG1 was checked, JAG1 expression was detected. Propofol-treated CCI rats were further injected with Ad-JAG1. Finally, the levels of JAG1 and Notch pathway-related proteins were detected. As a result, propofol could alleviate NP, including thermal hyperalgesia and mechanical pain threshold, and ameliorate neuroinflammation. Mechanically, propofol enhanced the level of miR-140-3p in CCI rats. JAG1 was a direct target of miR-140-3p. The downregulation of miR-140-3p or upregulation of JAG1 could reduce the protective effect of propofol against NP. Propofol inhibited activation of Notch signaling via miR-140-3p/JAG1. Overall, Propofol could inhibit the neuroinflammation and Notch signaling pathway via miR-140-3p/JAG1 to alleviate NP.

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