scholarly journals Antihyperalgesic Effect of Hesperidin Improves with Diosmin in Experimental Neuropathic Pain

2016 ◽  
Vol 2016 ◽  
pp. 1-12 ◽  
Author(s):  
Azucena I. Carballo-Villalobos ◽  
María-Eva González-Trujano ◽  
Francisco Pellicer ◽  
Francisco J. López-Muñoz
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Neuropathic Pain ◽  
Chronic Constriction Injury ◽  
Thermal Hyperalgesia ◽  
Primary Lesion ◽  
Antinociceptive Activity ◽  
Ms Analysis ◽  
Central Activity ◽  
Cci Model

Neuropathic pain is caused by a primary lesion, dysfunction, or transitory perturbation in the peripheral or central nervous system. In this study, we investigated the hesperidin antihyperalgesic effects alone or combined with diosmin in a model of neuropathic pain to corroborate a possible synergistic antinociceptive activity. Mechanical and thermal hyperalgesia were assessed in the aesthesiometer and plantar tests, respectively, after chronic constriction injury (CCI) model in rats receiving hesperidin (HS, 5 doses from 10 to 1000 mg/kg) alone or combined with diosmin (DS, 10 and 100 mg/kg) in comparison to gabapentin (31.6 mg/kg). UHPLC-MS analysis of cerebral samples was used to recognize the central concentrations of these flavonoids. Participation of different receptors was also investigated in the presence of haloperidol, bicuculline, and naloxone antagonists. Acute hesperidin administration significantly decreased mechanical and thermal hyperalgesia in CCI rats. Antihyperalgesic response of hesperidin, improved by a combination with diosmin (DS10/HS100) in both stimuli, was blockaded by haloperidol, bicuculline, and naloxone, but not WAY100635, antagonists. Both flavonoids were detected in brain samples. In conclusion, hesperidin alone and combined with diosmin produces antihyperalgesic response in the CCI model in rats. Antihyperalgesic effect of DS10/HS100 combination involves central activity partially modulated by D2,GABAA, and opioids, but not by 5-HT1A, receptors.

Long noncoding RNA GAS5 ameliorates chronic constriction injury induced neuropathic pain in rats by modulation of the miR-452-5p/CELF2 axis

2020 ◽  
Vol 98 (12) ◽  
pp. 870-877
Author(s):  
Yingjie Tian ◽  
Li Sun ◽  
Tao Qi
Keyword(s):  
Nervous System ◽  
Neuropathic Pain ◽  
Noncoding Rna ◽  
Chronic Constriction Injury ◽  
Pain Treatment ◽  
Thermal Hyperalgesia ◽  
Spontaneous Pain ◽  
Downstream Target ◽  
Tnf Α ◽  
The Central Nervous System

Neuropathic pain is a type of spontaneous pain that causes damage to the central nervous system. Long noncoding RNAs (lncRNAs) participate in the progression of various nervous system diseases, including neuropathic pain. However, the biological function of GAS5 in neuropathic pain remains unclear. Our findings revealed that GAS5 was downregulated in chronic constriction injury (CCI) rats. Besides, ELISA showed that the concentration of IL‐6, TNF-α, and IL‐1β were reduced by overexpressed GAS5 in spinal cord homogenates of CCI rats. Moreover, mechanical allodynia and thermal hyperalgesia in CCI rats were inhibited by GAS5 overexpression, suggesting that GAS5 overexpression attenuated neuropathic pain. Subsequently, we found that GAS5 served as a sponge for miR-452-5p in CCI rats and CELF2 was the downstream target of miR-452-5p. Finally, through a rescue assay, we found that GAS5 ameliorated neuropathic pain in CCI rats by sponging miR-452-5p to regulate CELF2 expression. Our study confirmed that GAS5 ameliorated neuropathic pain in rats by modulation of the miR-452-5p/CELF2 axis, which may provide some clues for neuropathic pain treatment.

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.

Anti-Neuropathic Pain Activity of Ageratum conyzoides L due to The Essential Oil Components

2020 ◽  
Vol 19 ◽  
Author(s):  
Yedy Purwandi Sukmawan ◽  
Kusnandar Anggadiredja ◽  
I Ketut Adnyana
Keyword(s):  
Neuropathic Pain ◽  
Essential Oil ◽  
Opioid Receptor ◽  
Steam Distillation ◽  
Chronic Constriction Injury ◽  
Thermal Hyperalgesia ◽  
Ageratum Conyzoides ◽  
Safety And Efficacy ◽  
Activity Test ◽  
Oil Components

Background: Neuropathic pain is one of the contributors to the global burdens of illness. At present many patients do not achieve satisfactory pain relief even with synthetic pain-killers. Taking this into consideration, it is necessary to search for natural product-derived alternative treatment with confirmed safety and efficacy. Ageratum conyzoides L is a plant often used as analgesic in Indonesia, however, anti-neuropathic pain activity of this plant is still unknown. Objective: To determine the anti-neuropathic pain activity of the essential oil and non-essential oil component (distillation residue) of A. conyzoides L. Methods: We conducted separation of the essential oil component from other secondary metabolites through steam distillation. Both components were tested for anti-neuropathic pain activity using chronic constriction injury animal models with thermal hyperalgesia and allodynia tests. The animals were divided into 7 test groups namely normal, sham, negative, positive (pregabalin at 0.195 mg/20 g BW of mice), essential oil component (100 mg/kg BW), and non-essential oil component (100 mg/kg BW). Naloxone was tested against the most potent anti-neuropathic pain component (essential oil or nonessential oil) to investigate the involvement of opioid receptor. Results: The GC-MS of the essential oil component indicated the presence of 60 compounds. Meanwhile, non-essential oil components contained alkaloid, flavonoid, polyphenol, quinone, steroid, and triterpenoid. This non-essential oil component contained a total flavonoid equivalent to 248.89 ppm quercetin. The anti-neuropathic pain activity test showed significantly higher activity of the essential oil component compared to the non-essential oil component and negative groups (p<0.05). Furthermore, the essential oil component showed equal activity to pregabalin (p>0.05). However, this activity was abolished by naloxone, indicating the involvement of opioid receptor in the action of the essential oil component. Conclusion: The essential oil component of A. conyzoides L is a potential novel substance for use as anti-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.

Understanding Neuropathic Pain

CNS Spectrums ◽  
2005 ◽  
Vol 10 (4) ◽  
pp. 298-308 ◽  
Author(s):  
Walter Zieglgänsberger ◽  
Achim Berthele ◽  
Thomas R. Tölle
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Neuropathic Pain ◽  
Neuronal Excitability ◽  
Traumatic Injury ◽  
Nerve Fibers ◽  
Cellular Events ◽  
Excitatory Neurotransmitters ◽  
The Central Nervous System ◽  
Activity Dependent

AbstractNeuropathic pain is defined as a chronic pain condition that occurs or persists after a primary lesion or dysfunction of the peripheral or central nervous system. Traumatic injury of peripheral nerves also increases the excitability of nociceptors in and around nerve trunks and involves components released from nerve terminals (neurogenic inflammation) and immunological and vascular components from cells resident within or recruited into the affected area. Action potentials generated in nociceptors and injured nerve fibers release excitatory neurotransmitters at their synaptic terminals such as L-glutamate and substance P and trigger cellular events in the central nervous system that extend over different time frames. Short-term alterations of neuronal excitability, reflected for example in rapid changes of neuronal discharge activity, are sensitive to conventional analgesics, and do not commonly involve alterations in activity-dependent gene expression. Novel compounds and new regimens for drug treatment to influence activity-dependent long-term changes in pain transducing and suppressive systems (pain matrix) are emerging.

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 Contemporary treatment neuropathic pain

2011 ◽  
Vol 64 (9-10) ◽  
pp. 443-447
Author(s):  
Milan Cvijanovic ◽  
Svetlana Simic ◽  
Sofija Banic-Horvat ◽  
Zita Jovin ◽  
Petar Slankamenac ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Neuropathic Pain ◽  
Phantom Limb Pain ◽  
Phantom Limb ◽  
Common Symptom ◽  
Chronic Neuropathic Pain ◽  
Cord Injury ◽  
The Central Nervous System ◽  
New Applications

Introduction. Neuropathic pain, or pain associated with disease or injury to the peripheral or central nervous system, is a common symptom of a heterogeneous group of conditions, including diabetic neuropathy, trigeminal neuralgia, postherpetic neuralgia and spinal cord injury. Chronic neuropathic pain should not be thought of as a symptom. It should truly be thought of as a disease with a very complicated pathophysiology. Pathophysiology. The mechanisms involved in neuropathic pain are complex and involve both peripheral and central pathophysiologic phenomenon. The underlying dysfunction may involve deafferentation within the peripheral nervous system (e.g. neuropathy), deafferentation within the central nervous system (e.g. post-thalamic stroke) or an imbalance between the two (e.g. phantom limb pain). Clinical characteristics. Neuropathic pain is non-nociceptive, in contrast to acute nociceptive pain, and it can be described as ?burning?, ?electric?, ?tingling?, and ?shooting? in nature. Treatment. Rational polypharmacy is often necessary and actually it is almost always the rule. It would be an exception if a patient was completely satisfied with his treatment. Treatment goals should include understanding that our patients may need to be titrated and managed with more than one agent and one type of treatment. There should be the balance of safety, efficacy, and tolerability. Conclusion. There are many new agents and new applications of the existing agents being currently studied which will most certainly lead to even more improved ways of managing this very complicated set of disorders.

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