Anti-hyperalgesic and anti-nociceptive potentials of standardized grape seed proanthocyanidin extract against CCI-induced neuropathic pain in rats

2016 ◽  
Vol 27 (1) ◽  
Author(s):  
Gurmanpreet Kaur ◽  
Onkar Bedi ◽  
Nidhika Sharma ◽  
Shamsher Singh ◽  
Rahul Deshmukh ◽  
...  
Keyword(s):  
Neuropathic Pain ◽  
Sciatic Nerve ◽  
Mechanical Allodynia ◽  
Biochemical Parameters ◽  
Thermal Hyperalgesia ◽  
Grape Seed ◽  
Spontaneous Pain ◽  
Post Surgery ◽  
Grape Seed Proanthocyanidin Extract ◽  
Grape Seed Proanthocyanidin

AbstractNeuropathic pain is associated with severe chronic sensory disturbances characterized by spontaneous pain, increased responsiveness to painful stimuli (hyperalgesia) and pain perceived in response to non-noxious stimuli (allodynia). Morphine is effective treatment for neuropathic pain but produces tolerance on chronic use. The present study was designed to explore the anti-nociceptive and anti-hyperalgesic effect of grape seed extract using sciatic nerve ligation-induced neuropathic pain in rats.Chronic constructive injury (CCI) was performed under anesthesia, on one side leg exposed by making a skin incision, and chromic gut ligatures were tied loosely around the sciatic nerve at 1 mm intervals. The treatment with grape seed proanthocyanidin extract (GSPE) (100 and 200 mg/kg, p.o.) was initiated on 7th day post-surgery and continued for next 14 days. Morphine (10 mg/kg, s.c.) alone and morphine in combination with GSPE (100 mg/kg, p.o.) were administered in CCI rats for 5 days starting from 7th day. On 3rd, 7th, 14th and 21st day, behavioral parameters (mechanical allodynia and thermal hyperalgesia) were assessed. Then the animals were killed on 22nd day and biochemical parameters [reduced glutathione (GSH), lipid peroxidation (LPO), catalase, nitrite, superoxide dismutase (SOD)] were assessed.Ligation of the sciatic nerve significantly induced mechanical allodynia and thermal hyperalgesia and induces oxidative stress (increase in LPO and nitrite) and decline of anti-oxidant enzyme levels (catalase, SOD, GSH) in sciatic nerve homogenate. GSPE (100 and 200 mg/kg, p.o.) attenuated all the behavioural and biochemical parameters. Morphine also significantly reversed the symptoms of neuropathic pain but produced tolerance after 5 days. Further, co-treatment of GSPE (100 mg/kg) with morphine (10 mg/kg, s.c.) in CCI rats significantly reversed the morphine tolerance and enhanced its anti-hyperalgesic effect as compared to the morphine-alone-treated group.In the present set of experiments, GSPE showed a significant anti-hyperalgesic and anti-nociceptive effect in rats.

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 Deletion of Acid-Sensing Ion Channel 3 Relieves the Late Phase of Neuropathic Pain by Preventing Neuron Degeneration and Promoting Neuron Repair

Cells ◽  
2020 ◽  
Vol 9 (11) ◽  
pp. 2355
Author(s):  
Chia-Chi Kung ◽  
Yi-Chu Huang ◽  
Ting-Yun Hung ◽  
Chih-Yu Teng ◽  
Tai-Ying Lee ◽  
...  
Keyword(s):  
Neuropathic Pain ◽  
Sciatic Nerve ◽  
Nerve Injury ◽  
Immune Cells ◽  
Mechanical Allodynia ◽  
Thermal Hyperalgesia ◽  
Persistent Pain ◽  
Neuron Degeneration ◽  
Ganglion Neurons ◽  
Atf3 Expression

Neuropathic pain is one type of chronic pain that occurs as a result of a lesion or disease to the somatosensory nervous system. Chronic excessive inflammatory response after nerve injury may contribute to the maintenance of persistent pain. Although the role of inflammatory mediators and cytokines in mediating allodynia and hyperalgesia has been extensively studied, the detailed mechanisms of persistent pain or whether the interactions between neurons, glia and immune cells are essential for maintenance of the chronic state have not been completely elucidated. ASIC3, a voltage-insensitive, proton-gated cation channel, is the most essential pH sensor for pain perception. ASIC3 gene expression is increased in dorsal root ganglion neurons after inflammation and nerve injury and ASIC3 is involved in macrophage maturation. ASIC currents are increased after nerve injury. However, whether prolonged hyperalgesia induced by the nerve injury requires ASIC3 and whether ASIC3 regulates neurons, immune cells or glial cells to modulate neuropathic pain remains unknown. We established a model of chronic constriction injury of the sciatic nerve (CCI) in mice. CCI mice showed long-lasting mechanical allodynia and thermal hyperalgesia. CCI also caused long-term inflammation at the sciatic nerve and primary sensory neuron degeneration as well as increased satellite glial expression and ATF3 expression. ASIC3 deficiency shortened mechanical allodynia and attenuated thermal hyperalgesia. ASIC3 gene deletion shifted ATF3 expression from large to small neurons and altered the M1/M2 macrophage ratio, thereby preventing small neuron degeneration and relieved pain.

Existence of Neuropathic Pain in Patients with Sickle Cell Disease

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 4254-4254
Author(s):  
Amanda M Brandow ◽  
Rebecca A. Farley ◽  
Julie A Panepinto
Keyword(s):  
Neuropathic Pain ◽  
Sickle Cell Disease ◽  
Pain Score ◽  
Sickle Cell ◽  
Mechanical Allodynia ◽  
Thermal Hyperalgesia ◽  
Spontaneous Pain ◽  
Cell Disease ◽  
Exact Test ◽  
Burning Pain

Abstract Abstract 4254 Background: Pain in sickle cell disease (SCD) increases with age and is often consistent with a chronic pain syndrome in adults. Patient descriptors of SCD pain (sharp, burning, shooting) and precipitating factors (cold temperatures, touch, increased wind speed and barometric pressure) suggest the existence of neuropathic pain. Neuropathic pain is defined as pain initiated or caused by a primary lesion or dysfunction of the nervous system that ultimately affects the somatosensory system. The prevalence of neuropathic pain in SCD is not well known. The objective of our study was to determine the presence of neuropathic pain in SCD patients, determine the sensory symptoms patients are experiencing, and to evaluate the relationship between neuropathic pain, age, and gender. We hypothesized 20% of SCD patients will report experiencing neuropathic pain and that neuropathic pain will be associated with older age and be more likely in females. Methods: A cross-sectional study was conducted in 56 patients with SCD. All patients ≥14 yrs (minimum age of questionnaire validation cohort) with a diagnosis of SCD were eligible and recruited during routine clinic visits while in their baseline state of health. The painDETECT questionnaire, a validated neuropathic pain screening tool developed to differentiate neuropathic from non-neuropathic pain, was used to measure neuropathic pain, the primary outcome of the study. The one-page questionnaire is comprised of 9 questions about the severity, course, and quality of pain specifically focused on neuropathic pain symptoms. Sensory symptoms of pain (burning pain, spontaneous paresthesias, mechanical allodynia, spontaneous pain attacks, thermal hyperalgesia, and numbness) were rated on a 0–5 scale. The questionnaire was scored based on the developer's guidelines and yielded a total score ranging from 0 to 38. Scores 19–38 indicate a definite neuropathic pain component, scores 0–12 indicate a neuropathic pain component does not exist, and scores 13–18 indicate a probable neuropathic pain component. Descriptive statistics were performed. Individual item responses of sensory symptoms graded 3 or higher were considered clinically relevant. Spearman correlation was used to determine the association of age and total score and Fisher's exact test was used to evaluate the difference in the proportion of patients with evidence of neuropathic pain between males and females. Results: Fifty-six SCD patients completed the questionnaire. Median age was 20.3 yrs (IQR 17–29), 77% were female, and genotypes were 64% HbSS, 25% HbSC, 4% HbSβ°thal, 4% HbSβ+thal, and 4% other. Mean hemoglobin was 9.8 (±1.7) g/dL, mean reticulocyte count was 7.8 (± 4.8) %, and 56% were on hydroxyurea. Mean pain score on a 0–10 scale at the time of study completion was 2.9 (±2.6), mean pain score during the past 4 weeks was 5.2 (±2.7) and 59% stated their pain radiated to other body regions from the primary pain site. We found 23% had a definite neuropathic pain component with scores ≥19 (range 19–28). An additional 14% had a probable neuropathic pain component with scores ranging between13–18. The proportions of patients reporting clinically relevant sensory symptoms were: spontaneous pain attacks (50%), mechanical allodynia (30%), numbness (29%), thermal hyperalgesia (27%), spontaneous paresthesias (27%), and burning pain (15%). Age was significantly positively correlated with total score [r=0.43; p=0.001] suggesting older patients have more neuropathic pain characteristics. There was no difference in the proportion of patients with definite or probable neuropathic pain scores between females and males [p=0.33; Fisher's exact test]. Only 4% of patients were taking Gabapentin, a drug used to treat neuropathic pain. Conclusions: Neuropathic pain exists in SCD. We found almost 40% of our SCD study population had a definite or probable component of neuropathic pain. The presence of neuropathic pain appears to increase with age since higher scores were significantly correlated with older age. Despite finding that almost 40% of patients experience neuropathic pain, less than 5% were taking a drug specifically targeted at treating neuropathic pain. Appropriate screening using validated tools can identify SCD patients that may benefit from therapies specifically targeted at treating neuropathic pain. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Co-Administration of Pioglitazone Improves Fluoxetine’s Antinociceptive, Neuroprotective, and Antidepressant Effects in Chronic Constriction Injury in Rats

2015 ◽  
Vol 6;18 (6;11) ◽  
pp. 609-620
Author(s):  
Hussam Murad
Keyword(s):  
Spinal Cord ◽  
Sciatic Nerve ◽  
Mechanical Allodynia ◽  
Sham Group ◽  
Chronic Constriction Injury ◽  
Thermal Hyperalgesia ◽  
Interleukin 10 ◽  
Monocyte Chemoattractant Protein 1 ◽  
Post Surgery ◽  
Antidepressant Effects

Background: Chronic pain may be associated with diabetes mellitus and/or depression. Use of therapies that target both comorbidities is encouraged. Objective: This study was designed to investigate the potential antinociceptive, neuroprotective, and antidepressant effects of combinations of pioglitazone or metformin with fluoxetine in chronic constriction injury (CCI) in rats. Study Design: Experimental trial in rats. Setting: University lab in Saudia Arabia. Methods: Two sets of experiments were performed. In each one, 9 groups of rats (n = 8) were used: sham, CCI, and 7 CCI-treated groups. Treatments were given orally starting on day 7 post-surgery as follows (mg/kg/day): fluoxetine (10, 20, and 40), pioglitazone (20), metformin (50), fluoxetine (20) + pioglitazone, and fluoxetine (20) + metformin. In the first set, on day 14 post-surgery mechanical allodynia, thermal hyperalgesia, and serum cytokines were measured. Moreover, immunoreactivity of glial fibrillary acidic protein (GFAP, a marker for astrocytic activation) in the spinal cord was assessed and histopathological changes in the ipsilateral sciatic nerve were examined. In the second set, on days 14 and 21 post-surgery the forced swimming test was done. Results: In the first set, all treatments significantly decreased mechanical allodynia while all treatments except F10 and F20 significantly decreased thermal hyperalgesia compared to the CCI group. The F20+M group showed the highest decreases, however still significantly lower than those of the sham group. The treatments didn’t impair motor function in the rotarod test. All treatments significantly decreased serum levels of tumor necrosis factor-α, interleukin-6, and monocyte chemoattractant protein-1 while increasing the level of interleukin-10. The CCI-induced marked increase of GFAP immunoexpression has been reduced to moderate with fluoxetine (40) and pioglitazone, and to mild with metformin and the combination groups. The CCI-induced changes in sciatic nerve were less in fluoxetine (40), pioglitazone, and metformin groups, and least in the combination groups. In the second set, the immobility duration was significantly reduced by F20, F40, P, F20+P, and F20+M compared to the CCI group. The F20+P group showed the highest decrease, however still significantly lower than that of the sham group. The treatments didn’t affect locomotor activity in the open field test. Limitations: Measuring the cytokines levels only in blood and not in the spinal cord and sciatic nerve and measuring the outcome measures in the first set of experiments at only one time-point. Conclusions: Co-administration of pioglitazone or metformin with low-dose fluoxetine improved mechanical allodynia, thermal hyperalgesia, and neurohistopathological changes while coadministration of pioglitazone, but not metformin, improved the depressive-like behavior in the peripheral nerve injury model of neuropathic pain in rats. Extrapolation of the current results to clinical reality could be beneficial for pain patients with diabetes and/or depression, however this needs further confirmatory studies. Key words: Antidepressant, antinociceptive, chronic constriction injury, fluoxetine, GFAP, metformin, neuroprotective, pain, pioglitazone, sciatic

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.

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