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 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 Comparative efficacy of pregabalin and baclofen in the rodent chronic constriction injury model of neuropathic pain

2018 ◽  
Vol 8 (1) ◽  
pp. 133
Author(s):  
Saurabh Kohli ◽  
Taruna Sharma ◽  
Juhi Kalra ◽  
Dilip C. Dhasmana
Keyword(s):  
Neuropathic Pain ◽  
Sciatic Nerve ◽  
Chronic Constriction Injury ◽  
Thermal Hyperalgesia ◽  
Mechanical Hyperalgesia ◽  
Comparative Efficacy ◽  
First Line ◽  
Injury Model ◽  
Different Types ◽  
Chronic Constriction Injury Model

Background: Neuropathic pain is associated with prolonged disability and is usually not responsive to conventional analgesics like NSAIDs and opioids. Even the recommended first-line drugs are effective in less than 50% patients. Thus, drugs with different mechanisms of action are needed. Baclofen, a GABA-B agonist has shown benefit in different types of neuropathic pains and is compared against pregabalin.Methods: The sciatic nerve was ligated in 2 groups of 6 rats each as per the chronic constriction injury model of neuropathic pain on day 0. After 14 days the effect of single doses of pregabalin (30mg/kg) and baclofen (5mg/kg) intraperitoneally were assessed over a 2 hours period. Thermal and mechanical hyperalgesia were assessed as measures of neuropathic pain by the hotplate and pin-prick method respectively.Results: Significant thermal and mechanical hyperalgesia was produced 14 days after sciatic nerve ligation in both the groups (p <0.05). Both pregabalin (p <0.001) and baclofen (p <0.01) were effective in decreasing thermal hyperalgesia throughout the two hours study period, but pregabalin was more effective as compared to baclofen (p <0.05) at 30, 60 and 120minutes. Both the drugs produced a significant decrease in mechanical hyperalgesia (p <0.01) throughout the study period. Again, pregabalin was the more effective drug (p <0.05) at all time points.Conclusions: Significant thermal and mechanical hyperalgesia was seen 14 days after sciatic nerve ligation. Both pregabalin and baclofen were effective in reversing the hyperalgesia, but pregabalin was the more effective of the two drugs at all time points.

scholarly journals Ameliorative potential of Butea monosperma on chronic constriction injury of sciatic nerve induced neuropathic pain in rats

2012 ◽  
Vol 84 (4) ◽  
pp. 1091-1104 ◽  
Author(s):  
Venkata R.K. Thiagarajan ◽  
Palanichamy Shanmugam ◽  
Uma M. Krishnan ◽  
Arunachalam Muthuraman ◽  
Nirmal Singh
Keyword(s):  
Neuropathic Pain ◽  
Sciatic Nerve ◽  
Chronic Constriction Injury ◽  
Thermal Hyperalgesia ◽  
Ethanolic Extract ◽  
Thiobarbituric Acid ◽  
Positive Control ◽  
Nerve Tissue ◽  
Dependent Manner ◽  
Butea Monosperma

The present study was designed to investigate the ameliorative role of ethanolic extract from leaves of Butea monosperma in chronic constriction injury (CCI) of sciatic nerve induced neuropathic pain in rats. Hot plate, acetone drop, paw pressure, Von Frey hair and tail immersion tests were performed to assess the degree of thermal hyperalgesia, cold chemical allodynia, mechanical hyperalgesia & allodynia in the left hind paw and tail thermal hyperalgesia. Further on, thiobarbituric acid reactive substances (TBARS), reduced glutathione (GSH) and total calcium levels were estimated to assess the biochemical changes in the sciatic nerve tissue. Histopathological changes were also observed in the sciatic nerve tissue. Ethanolic extract of Butea monosperma leaves and pregabalin (serving as positive control) were administered for 14 consecutive days starting from the day of surgery. CCI resulted in significant changes in behavioural and biochemical parameters. Pretreatment of Butea monosperma attenuated CCI induced development of behavioural, biochemical and histopathological alterations in a dose dependent manner, which is comparable to that of pregabalin pretreated group. These findings may be attributed to its potential anti-oxidative, neuroprotective and calcium channel modulatory actions of Butea monosperma.

Differential Effects of Intrathecally Administered Morphine and Its Interaction with Cholecystokinin-B Antagonist on Thermal Hyperalgesia following Two Models of Experimental Mononeuropathy in the Rat 

1999 ◽  
Vol 90 (5) ◽  
pp. 1382-1391 ◽  
Author(s):  
Tatsuo Yamamoto ◽  
Yoshihiko Sakashita
Keyword(s):  
Neuropathic Pain ◽  
Sciatic Nerve ◽  
Nerve Injury ◽  
Chronic Constriction Injury ◽  
Thermal Hyperalgesia ◽  
Sciatic Nerve Injury ◽  
Morphine Analgesia ◽  
Injury Model ◽  
The Right

Background Cholecystokinin-B receptor activation has been reported to reduce morphine analgesia. Neuropathic pain is thought to be relatively refractory to opioids. One possible mechanisms for a reduced effect of morphine on neuropathic pain is the induction of cholecystokinin in the spinal cord by nerve injury. The authors evaluated the role of the spinal cholecystokinin-B receptor on morphine analgesia in two rat neuropathic pain models: chronic constriction injury and partial sciatic nerve injury. Methods A chronic constriction injury is created by placing four loosely tied ligatures around the right sciatic nerve. A partial sciatic nerve injury was created by tight ligation of one third to one half of the right sciatic nerve. All drugs were injected intrathecally 7 and 11 days after the nerve injury. The effect of the drugs was reflected in the degree of paw withdrawal latency to thermal nociceptive stimulation. The paw withdrawal latencies of injured and uninjured paws were measured 5, 15, 30, and 60 min after the drugs were injected. Results In the chronic constriction injury model, intrathecal morphine increased the paw withdrawal latencies of injured and uninjured paws. PD135158, a cholecystokinin-B receptor antagonist, potentiated the analgesic effect of morphine on injured and uninjured paws. In the partial sciatic nerve injury model, the effect of morphine on the injured paw was less potent than that on the uninjured paw, and PD135158 potentiated the morphine analgesia in the uninjured paw and had only a minor effect on the morphine analgesia in the injured paw. Conclusions The effectiveness of morphine for thermal hyperalgesia after nerve injury depends on the type of nerve injury. The role of the cholecystokinin-B receptor in morphine analgesia in thermal hyperalgesia after nerve injury also depends on the type of nerve injury.

scholarly journals Evaluating the Effects of Probiotic Supplementation on Neuropathic Pain and Oxidative Stress Factors in an Animal Model of Chronic Constriction Injury of the Sciatic Nerve

2021 ◽  
Vol 0 (0) ◽  
pp. 1-19
Author(s):  
Mohammad Shabani ◽  
◽  
Elham Hasanpour ◽  
Mojgan Mohammadifar ◽  
Fereshteh Bahmani ◽  
...  
Keyword(s):  
Neuropathic Pain ◽  
Sciatic Nerve ◽  
Antioxidant Capacity ◽  
Chronic Constriction Injury ◽  
Thermal Hyperalgesia ◽  
Lactobacillus Delbrueckii ◽  
Stress Factors ◽  
Male Rats ◽  
Probiotic Treatment ◽  
Cci Model

Background: Neuropathic pain is a common and painful somatosensory nervous system disease, and its treatment remains a medical challenge. Evidence demonstrates that gut microbiota alters in neuropathic pain and, therefore, improvement of the gut flora may affect the disease. The present study aimed to evaluate the antinociceptive effect of probiotics in neuropathic pain and oxidative biomarkers' responsiveness to the probiotic treatment. Methods: Using chronic constriction injury (CCI) of the rats' sciatic nerve, neuropathic pain was induced. Investigating the analgesic effect of the probiotics mixture, 40 male rats were randomly assigned to 4 groups (n=10 for each): Sham-operated (SM), and CCI model rats have orally received 1 ml saline (CS), or 100 mg/kg Gabapentin (CG) or 1 ml probiotics mixture (CP) Lactobacillus plantarum, Lactobacillus delbrueckii, Lactobacillus acidophilus, Lactobacillus rhamnosus, and Bifidobacterium bifidum (109 CFU of each) daily. Using behavioral tests, the pain was assessed on days 1, 4, 7, 14, and 21 of the study. Finally, the biochemical evaluation of sciatic nerve tissue was done. Results: Probiotics decreased cold and mechanic allodynia and thermal hyperalgesia. Reducing lipid peroxidation level and increasing total antioxidant capacity, SOD, and GPx activity was also significant in the probiotics group. Conclusions: These findings suggest that probiotics have analgesic effects on the chronic constriction injury (CCI) model of neuropathic pain via increasing antioxidant capacity of the rats' sciatic nerve.

scholarly journals Neuroprotective and Anti-Inflammatory Activities of Atorvastatin in a Rat Chronic Constriction Injury Model

2012 ◽  
Vol 25 (1) ◽  
pp. 219-230 ◽  
Author(s):  
L.W. Chu ◽  
J.Y. Chen ◽  
K.L. Yu ◽  
K.I. Cheng ◽  
I.J. Chen ◽  
...  
Keyword(s):  
Neuropathic Pain ◽  
Sciatic Nerve ◽  
Chronic Constriction Injury ◽  
Thermal Hyperalgesia ◽  
Dependent Manner ◽  
Sprague Dawley ◽  
Neuroprotective Effects ◽  
Peripheral Neuropathic Pain ◽  
Anti Inflammatory ◽  
Coa Reductase

Atorvastatin is an HMG-CoA reductase inhibitor used to treat hypercholesterolemic conditions associated with hypertension. This study aims to investigate the anti-inflammatory and neuroprotective effects of atorvastatin on peripheral neuropathic pain. Peripheral neuropathic pain was induced by chronic constriction injury (CCI) in Sprague-Dawley rats. Rats were divided into 3 groups including sham-operated, CCI, and atorvastatin-treated. Atorvastatin (10 mg/kg) or phosphate-buffered saline was orally administered for 2 weeks. All animals were assessed by neurobehavioral tests before surgery and at days 3, 7, 14 after surgery. Inflammatory and neuroprotective factors were evaluated by Western blot analysis. eNOS, COX2 and iNOS in the sciatic nerve were also studied using immunohistochemistry. Atorvastatin attenuated CCI-induced nociceptive sensitization and thermal hyperalgesia in a time-dependent manner. Atorvastatin improved CCI-induced neurobehavioral/inflammatory activity by inhibition of TGF-β, PIκB/IκB, NFκB, COX2, iNOS, EP1 and EP4 in the sciatic nerve. Atorvastatin was also found to increase neuroprotection factors pAkt/Akt, eNOS and VEGF. Taken together, these data indicate that atorvastatin could protect the sciatic nerve against CCI-induced neuroinflammation and nociception.

scholarly journals Hypoalgesic effect of Spirulina platensis on the sciatic neuropathic pain induced by chronic constriction injury in male rats

2018 ◽  
Vol 5 (9) ◽  
pp. 2671-2679 ◽  
Author(s):  
Hossein Ali Safakhah ◽  
Farzaneh Tamimi ◽  
Nasroallah Moradi kor ◽  
Ahmad Reza Bandegi ◽  
Ali Ghanbari
Keyword(s):  
Neuropathic Pain ◽  
Sciatic Nerve ◽  
Spirulina Platensis ◽  
Mechanical Allodynia ◽  
Chronic Constriction Injury ◽  
Thermal Hyperalgesia ◽  
Male Rats ◽  
Intragastric Administration ◽  
Post Surgery ◽  
Reducing Ability

Background: It has been revealed that herbal medicines have a palliative effect on pain. In the present study, the hypoalgesic effect of Spirulina platensis (microalgae) on the neuropathic pain induced by chronic constriction injury (CCI) was investigated. Methods: In the present study, 74 adult male Wistar rats weighing 200-220 grams were used. For inducing neuropathic pain, CCI was performed on the left sciatic nerve. Spirulina platensis was intragastrically administered daily for 3 weeks. Mechanical allodynia and thermal hyperalgesia were assessed by Von Frey hairs and plantar test device, respectively. Malondialdehyde (MDA) and total antioxidant capacity (TOC) were detected in the serum using thiobarbituric acid and ferric reducing ability of plasma (FRAP), respectively. Results: CCI of the sciatic nerve led to mechanical allodynia and thermal hyperalgesia at three weeks as well as two weeks post surgery. Three weeks of Spirulina therapy significantly (P<0.05) decreased paw withdrawal response to mechanical and thermal stimulations, compared to control. FRAP, but not MDA, significantly decreased three weeks after CCI, and Spirulina therapy significantly reversed its level towards control. Conclusion: Chronic intragastric administration of Spirulina platensis alleviates CCI-induced neuropathic pain by modulating oxidative stress through increasing FRAP levels in male rats.

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.

Prevention and Healing of Calcium Signaling Mediated Neuronal Damage on successive Administration of Flavonoid Enriched Pterocarpus Marsupium Roxb in Peripheral Neuropathy Model

2020 ◽  
Vol 16 (9) ◽  
pp. 1346-1355
Author(s):  
Neethi Shaju ◽  
Mrinmoy Gautam ◽  
Abdul Khayum ◽  
Gunasekaran Venkatesh
Keyword(s):  
Neuropathic Pain ◽  
Peripheral Neuropathy ◽  
Sciatic Nerve ◽  
Motor Neurons ◽  
Neuronal Damage ◽  
Interleukin 10 ◽  
Central Mechanism ◽  
Behavioral Models ◽  
Cell Hyperplasia ◽  
Pterocarpus Marsupium

Background: Modern research on peripheral neuropathy circumstance utter that treatments with Vincristine (VCR) disturb the microtubular cells in sensory and motor neurons due to calcium over- load in sciatic nerve, unfortunately, VCR triggering the release of Tumor necrosis factor-α (TNFα) in central neurons causes excitotoxicity as well. Although ethnomedical information specifies that Pterocarpus marsupium Roxb (PM) is widely used for various nervous disorders, not yet justified on VCR induced peripheral neuropathy and in relation to central mechanism. Objective: This study is aimed to explore the possible central and peripheral mechanism of flavonoid enriched PM in VCR induced neuropathy model. Methods: Neuropathic pain was induced in female Wistar rats by VCR (75μg/ kg/day, i.p) for 10 days. Nociceptive thresholds were assessed by subjecting them to behavioral and biochemical estimation, proinflammatory cytokines along with morphological evaluation. Results: PM significantly increased the nociceptive threshold evident from various behavioral models in comparison to VCR group. More importantly, PM significantly reversed the VCR induced calcium elevation, glutamate and aspartate release in the brain. Discussion: It was also observed that the raised TNF-α, Interleukin-1β were controlled and interleukin- 10 was elevated in sciatic nerve after PM treatment. Evident from histology, PM markedly reversed the VCR induced axonal degeneration, Schwann cell hyperplasia, and myelin fibrosis. Conclusion: Flavonoid enriched PM both 100 & 200mg/kg post and co-administration exerted a preventive and curative effect in VCR induced neuropathic pain by controlling calcium-mediated excitotoxicity through peripheral and central mechanism.

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