Silencing of IRF3 alleviates chronic neuropathic pain following chronic constriction injury

2017 ◽  
Vol 88 ◽  
pp. 403-408 ◽  
Author(s):  
Rui Li ◽  
Li-guo Wang ◽  
Qi Wang ◽  
Zhi-hua Li ◽  
Ya-li Ma ◽  
...  
Keyword(s):  
Neuropathic Pain ◽  
Chronic Constriction Injury ◽  
Chronic Neuropathic Pain

scholarly journals Alpha lipoic acid attenuated neuropathic pain induced by chronic constriction Injury of sciatic nerve in rats

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Prasad Neerati ◽  
Harika Prathapagiri
Keyword(s):  
Neuropathic Pain ◽  
Peripheral Neuropathy ◽  
Sciatic Nerve ◽  
Lipoic Acid ◽  
Normal Saline ◽  
Chronic Constriction Injury ◽  
Thermal Hyperalgesia ◽  
Alpha Lipoic Acid ◽  
Chronic Neuropathic Pain ◽  
Neuropathic Pain Syndrome

Abstract Background Chronic neuropathic pain syndrome is associated with impaired quality of life and is poorly manageable. Alpha lipoic acid (ALA) is a powerful antioxidant and showed its effectiveness on diabetic neuropathy and other acute peripheral nerve injuries but it was not evaluated in the chronic neuropathic pain, chronic constriction injury (CCI) in rat model by using duloxetine (DLX) as standard. Methodology The main objective of the study was to expedite ALA effect on chronic peripheral neuropathy induced by CCI of sciatic nerve in rats. In this study, male Wister rats were randomly divided into six groups (n = 8) including, normal saline, sham operated, surgery control, DLX 30mg/kg treated, ALA treated 25mg/kg, and ALA+DLX. The CCI of sciatic nerve was conducted on all animals except normal saline group and studied for 21 days (i.e. 14 days treatment period & 7 days treatment free period) by using different behavioral, biochemical and, histopathology studies. Results ALA showed minor but significant decrease of thermal hyperalgesia, cold allodynia, malondialdehyde (MDA), total protein, lipid peroxidation, and nitric oxide levels and significant increase of motor coordination, glutathione level and decreased axonal degeneration significantly. These effects sustained even during treatment free period. ALA enhanced the effect of DLX when given in combination by showing sustained effect. In conclusion, ALA acted as potent antioxidant may be this activity is responsible for the potent neuroprotective effect. Conclusion Hence, ALA attenuated the nueroinflammation mediated by chronic peripheral neuropathy. Further studies are warranted with ALA to develop as a clinically relevant therapeutic agent for the treatment of neuropathic pain.

scholarly journals ERK activation in noradrenergic and serotonergic brainstem nuclei in chronic pain upon noxious stimulation and antidepressants treatment

2009 ◽  
Vol 15 (S3) ◽  
pp. 7-8
Author(s):  
G. Borges ◽  
E. Berrocoso ◽  
A. Ortega-Alvaro ◽  
J. A. Micó ◽  
F. L. Neto
Keyword(s):  
Chronic Pain ◽  
Neuropathic Pain ◽  
Chronic Constriction Injury ◽  
Noxious Stimulation ◽  
Analgesic Action ◽  
Chronic Neuropathic Pain ◽  
Erk Activation ◽  
Pain Transmission ◽  
Extracellular Signal ◽  
Brainstem Nuclei

AbstractChronic neuropathic pain is a pathology that affects thousands of people worldwide. Antidepressants have been prescribed for the treatment of this sort of pain but the mechanisms underlying their analgesic action remain unknown. Extracellular-signal regulated kinases (ERKs) are being implicated in pain transmission and modulation as well as in the pathophysiology of depression. In order to clarify some of the mechanisms which might be related to the analgesic effect of antidepressants, we started by evaluating possible changes in the pattern of activation of ERKs in rats with chronic constriction injury (CCI), an experimental model of chronic

scholarly journals TNFR2 promotes Treg-mediated recovery from neuropathic pain across sexes

2019 ◽  
Vol 116 (34) ◽  
pp. 17045-17050 ◽  
Author(s):  
Roman Fischer ◽  
Maksim Sendetski ◽  
Tania del Rivero ◽  
George F. Martinez ◽  
Valerie Bracchi-Ricard ◽  
...  
Keyword(s):  
Neuropathic Pain ◽  
Immune Modulation ◽  
Chronic Constriction Injury ◽  
Tumor Necrosis Factor Receptor ◽  
Spontaneous Pain ◽  
Neuronal Regeneration ◽  
Chronic Neuropathic Pain ◽  
Genetic Deletion ◽  
Necrosis Factor

Tumor necrosis factor receptor 2 (TNFR2) is a transmembrane receptor that is linked to immune modulation and tissue regeneration. Here, we show that TNFR2 essentially promotes long-term pain resolution independently of sex. Genetic deletion of TNFR2 resulted in impaired neuronal regeneration and chronic nonresolving pain after chronic constriction injury (CCI). Further, pharmacological activation of TNFR2 using the TNFR2 agonist EHD2-sc-mTNFR2 in mice with chronic neuropathic pain promoted long-lasting pain recovery. TNFR2 agonist treatment reduced neuronal injury, alleviated peripheral and central inflammation, and promoted repolarization of central nervous system (CNS)-infiltrating myeloid cells into an antiinflammatory/reparative phenotype. Depletion of regulatory T cells (Tregs) delayed spontaneous pain recovery and abolished the therapeutic effect of EHD2-sc-mTNFR2. This study therefore reveals a function of TNFR2 in neuropathic pain recovery and demonstrates that both TNFR2 signaling and Tregs are essential for pain recovery after CCI. Therefore, therapeutic strategies based on the concept of enhancing TNFR2 signaling could be developed into a nonopioid therapy for the treatment of chronic neuropathic pain.

scholarly journals Verification of neuroprotective effects of alpha-lipoic acid on chronic neuropathic pain in a chronic constriction injury rat model

2021 ◽  
Vol 16 (1) ◽  
pp. 222-228
Author(s):  
Junhao Wang ◽  
Zhaohui Lou ◽  
Haiyang Xi ◽  
Zhi Li ◽  
Lepeng Li ◽  
...  
Keyword(s):  
Neuropathic Pain ◽  
Lipoic Acid ◽  
Rat Model ◽  
Chronic Constriction Injury ◽  
Neuroprotective Effect ◽  
Alpha Lipoic Acid ◽  
Chronic Neuropathic Pain ◽  
Neuroprotective Effects ◽  
Satellite Glial Cells ◽  
Withdrawal Threshold

Abstract Treatment of neuropathic pain is far from satisfactory. This study sought evidence of a neuroprotective effect of alpha-lipoic acid (ALA) to treat neuropathic pain in a chronic constriction injury (CCI) rat model. A total of 48 rats were randomly divided into sham, CCI, or CCI + ALA groups. Mechanical and thermal nociceptive thresholds were evaluated as behavioral assessments. Dorsal root ganglia cells were assessed morphologically with hematoxylin and eosin staining and for apoptosis with P53 immunohistochemical staining. Compared with the sham group, the CCI group had a shorter paw withdrawal threshold and paw withdrawal latency, abnormal morphologic manifestations, and increased numbers of satellite glial cells and P53+ cells. These changes were significantly reversed by treatment with ALA. Our study indicates neuroprotective effects of ALA on chronic neuropathic pain in a CCI rat model. ALA is potentially considered to be developed as a treatment for neuropathic pain caused by peripheral nerve injury, which requires further verification.

scholarly journals Thymus algeriensis and Thymus fontanesii exert neuroprotective effect against chronic constriction injury-induced neuropathic pain in rats

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Samar Rezq ◽  
Amira E. Alsemeh ◽  
Luigi D’Elia ◽  
Assem M. El-Shazly ◽  
Daria Maria Monti ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Neuropathic Pain ◽  
Sciatic Nerve ◽  
Caspase 3 ◽  
Chronic Constriction Injury ◽  
Hacat Cells ◽  
Protective Effects ◽  
Chronic Neuropathic Pain ◽  
Thymus Algeriensis ◽  
Post Surgery

AbstractWe have previously demonstrated that the Thymus algeriensis and Thymus fontanesii extracts have powerful anti-inflammatory, antipyretic, and analgesic effects against acute pain models. We profiled their chemical composition and found many phenolic acids, flavonoids, and phenolic diterpenes. In this work, we investigated their antioxidant properties on HaCaT cells exposed to UVA-induced oxidative stress and examined their effects against chronic neuropathic pain and the underlying mechanisms. Through a rat chronic constriction injury (CCI) model, we induced chronic neuropathic pain by placing 4 loose ligatures around the right sciatic nerve for 14 days. Thermal and mechanical hyperalgesia in addition to cold and dynamic allodynia were tested on the day before surgery and on the 7th and 14th post-surgery days. Key markers of the nitrosative and oxidative stresses, in addition to markers of inflammation, were measured at day 14 post surgery. Histopathological examination and immunostaining of both synaptophysin and caspase-3 of sciatic nerve and brain stem were also performed. Results of this study showed that T. algeriensis extract suppresses UVA oxidative stress in HaCaT cells via activation of the Nrf-2 pathway. Both extracts attenuated hyperalgesia and allodynia at 7- and 14-days post-surgery with more prominent effects at day 14 of surgery. Their protective effects against neuropathic pain were mediated by inhibiting NOX-1, iNOS, by increasing the enzyme activity of catalase, and inhibition of inflammatory mediators, NF-κB, TNF-α, lipoxygenase, COX-2 enzymes, and PGE2. Furthermore, they improved deleterious structural changes of the brainstem and sciatic nerve. They also attenuated the increased caspase-3 and synaptophysin. The data indicate that both extracts have neuroprotective effects against chronic constriction injury-induced neuropathic pain. The observed protective effects are partially mediated through attenuation of oxidative and nitrosative stress and suppression of both neuroinflammation and neuronal apoptosis, suggesting substantial activities of both extracts in amelioration of painful peripheral neuropathy.

scholarly journals Effects of Chronic Electroacupuncture on Depression- and Anxiety-Like Behaviors in Rats with Chronic Neuropathic Pain

2014 ◽  
Vol 2014 ◽  
pp. 1-10 ◽  
Author(s):  
Qian Li ◽  
Na Yue ◽  
Shen-Bin Liu ◽  
Zhi-Fu Wang ◽  
Wen-Li Mi ◽  
...  
Keyword(s):  
Neuropathic Pain ◽  
Forced Swimming Test ◽  
Chronic Constriction Injury ◽  
Elevated Plus Maze ◽  
Depression And Anxiety ◽  
Chronic Neuropathic Pain ◽  
Behavioral Deficits ◽  
Plus Maze ◽  
Swimming Test

Growing evidence indicates that chronic neuropathic pain is frequently accompanied by an array of psychiatric diseases, such as depression and anxiety. Electroacupuncture (EA), as one therapy of traditional Chinese medicine, has displayed potent antidepressant-like effects in numerous clinical studies. The present study was designed to examine the possible effects of EA on the depressive and anxiety disorders induced by neuropathic pain. A classic rat model of neuropathic pain was produced by chronic constriction injury (CCI) of the sciatic nerve. EA was performed on acupoints “Bai-Hui” (GV20) and unilateral “Yang-Ling-Quan” (GB34). The antidepressive and anxiolytic effects of EA treatment were analyzed using the forced swimming test (FST) and the elevated plus maze (EPM) test, respectively. CCI resulted in remarkable depression- and anxiety-like behaviors, whereas the chronic EA treatment significantly improved the behavioral deficits of CCI rats. Moreover, the phosphorylation level of the NMDA receptor type 1 (NR1) subunit was decreased in the hippocampus of CCI rats. Intriguingly, continuous EA treatment effectively blocked this decrease in the levels of pNR1. These results suggested that EA has antidepressive and anxiolytic effects on rats with neuropathic pain and that this might be associated with restoring the phosphorylation of NR1 in the hippocampus.

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