Neuroprotective effect of saponin rich extract of Acorus calamus L. in rat model of chronic constriction injury (CCI) of sciatic nerve-induced neuropathic pain

In this study, the phytochemical composition and the possible prophylactic effects of an aqueous ethanol extract of Haematoxylon campechianum flowers (HCF) on peripheral neuropathic pain in a chronic constriction injury (CCI) rat model are investigated. Rats with induced CCI were subjected to neuropathic pain behaviour tests and evaluated by chemical, thermal, and mechanical sensation tests and functional recovery of the brain stem and sciatic nerve at 7- and 14-day intervals. The effect of the extract on acute pain and inflammation is also investigated. The extract exerted both peripheral and central analgesic and anti-inflammatory properties in addition to antipyretic effects that are clear from targeting COX, LOX and PGE. It was found that CCI produced significant thermal and mechanical hyperalgesia, cold allodynia and deleterious structural changes in both sciatic nerve and brain stem. Treatments with HCF extract significantly improved cold and thermal withdrawal latency, mechanical sensibility and ameliorated deleterious changes of sciatic nerve and brain stem at different dose levels. The extract also ameliorated oxidative stress and inflammatory markers in brain stem and sciatic nerve. It suppressed the apoptotic marker, p53, and restored myelin sheath integrity. The effects of HCF extract were more potent than pregabalin. Fifteen secondary metabolites, mainly gallotannins and flavonoids, were characterized in the extract based on their retention times and MS/MS data. The identified phenolic constituents from the extract could be promising candidates to treat neuropathic pain due to their diverse biological activities, including antioxidant, anti-inflammatory and neuroprotective properties.

Download Full-text

1,3,4-Oxadiazole Derivative Attenuates Chronic Constriction Injury Induced Neuropathic Pain: A Computational, Behavioral, and Molecular Approach

Brain Sciences ◽

10.3390/brainsci10100731 ◽

2020 ◽

Vol 10 (10) ◽

pp. 731

Author(s):

Muhammad Faheem ◽

Syed Hussain Ali ◽

Abdul Waheed Khan ◽

Mahboob Alam ◽

Umair Ilyas ◽

...

Keyword(s):

Spinal Cord ◽

Neuropathic Pain ◽

Sciatic Nerve ◽

Pain Perception ◽

Chronic Constriction Injury ◽

Neuroprotective Effect ◽

Underlying Mechanism ◽

Contributing Factors ◽

Neuroprotective Effects ◽

In Silico Studies

The production and up-regulation of inflammatory mediators are contributing factors for the development and maintenance of neuropathic pain. In the present study, the post-treatment of synthetic 1,3,4 oxadiazole derivative (B3) for its neuroprotective potential in chronic constriction injury-induced neuropathic pain was applied. In-silico studies were carried out through Auto Dock, PyRx, and DSV to obtain the possible binding and interactions of the ligands (B3) with COX-2, IL-6, and iNOS. The sciatic nerve of the anesthetized rat was constricted with sutures 3/0. Treatment with 1,3,4-oxadiazole derivative was started a day after surgery and continued until the 14th day. All behavioral studies were executed on day 0, 3rd, 7th, 10th, and 14th. The sciatic nerve and spinal cord were collected for further molecular analysis. The interactions in the form of hydrogen bonding stabilizes the ligand target complex. B3 showed three hydrogen bonds with IL-6. B3, in addition to correcting paw posture/deformation induced by CCI, attenuates hyperalgesia (p < 0.001) and allodynia (p < 0.001). B3 significantly raised the level of GST and GSH in both the sciatic nerve and spinal cord and reduced the LPO and iNOS (p < 0.001). B3 attenuates the pathological changes induced by nerve injury, which was confirmed by H&E staining and IHC examination. B3 down-regulates the over-expression of the inflammatory mediator IL-6 and hence provides neuroprotective effects in CCI-induced pain. The results demonstrate that B3 possess anti-nociceptive and anti-hyperalgesic effects and thus minimizes pain perception and inflammation. The possible underlying mechanism for the neuroprotective effect of B3 probably may be mediated through IL-6.

Download Full-text

Neuroprotective Effect of Anethole Against Neuropathic Pain Induced by Chronic Constriction Injury of the Sciatic Nerve in Mice

Neurochemical Research ◽

10.1007/s11064-018-2668-7 ◽

2018 ◽

Vol 43 (12) ◽

pp. 2404-2422 ◽

Cited By ~ 6

Author(s):

Bing Wang ◽

Guoxin Zhang ◽

Mei Yang ◽

Ning Liu ◽

Yu-Xiang Li ◽

...

Keyword(s):

Neuropathic Pain ◽

Sciatic Nerve ◽

Chronic Constriction Injury ◽

Neuroprotective Effect

Download Full-text

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

Open Life Sciences ◽

10.1515/biol-2021-0026 ◽

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.

Download Full-text

Retrograde Labeling of Different Distribution Features of DRG P2X2 and P2X3 Receptors in a Neuropathic Pain Rat Model

BioMed Research International ◽

10.1155/2020/9861459 ◽

2020 ◽

Vol 2020 ◽

pp. 1-15

Author(s):

Lin Chen ◽

Changlong Leng ◽

Qin Ru ◽

Qi Xiong ◽

Mei Zhou ◽

...

Keyword(s):

Neuropathic Pain ◽

Sciatic Nerve ◽

Rat Model ◽

Dorsal Root ◽

Chronic Constriction Injury ◽

P2x Receptors ◽

Drg Neurons ◽

P2x3 Receptors ◽

Peripheral Neuropathic Pain ◽

Distribution Features

The distributions of P2X subtypes during peripheral neuropathic pain conditions and their differential roles are not fully understood. To explore these characteristics, the lumbosacral dorsal root ganglion (DRG) in the chronic constriction injury (CCI) sciatic nerve rat model was studied. Retrograde trace labeling combined with immunofluorescence technology was applied to analyze the distribution of neuropathic nociceptive P2X1-6 receptors. Our results suggest that Fluoro-Gold (FG) retrograde trace labeling is an efficient method for studying lumbosacral DRG neurons in the CCI rat model, especially when the DRG neurons are divided into small, medium, and large subgroups. We found that neuropathic nociceptive lumbosacral DRG neurons (i.e., FG-positive cells) were significantly increased in medium DRG neurons, while they declined in the large DRG neurons in the CCI group. P2X3 receptors were markedly upregulated in medium while P2X2 receptors were significantly decreased in small FG-positive DRG neurons. There were no significant changes in other P2X receptors (including P2X1, P2X4, P2X5, and P2X6). We anticipate that P2X receptors modulate nociceptive sensitivity primarily through P2X3 subtypes that are upregulated in medium neuropathic nociceptive DRG neurons and/or via the downregulation of P2X2 cells in neuropathic nociceptive small DRG neurons.

Download Full-text

Effect of Umbelliprenin on antinociceptive activity of morphine in a rat model of neuropathic pain induced by chronic constriction injury of the sciatic nerve

The Natural Products Journal ◽

10.2174/2210315510999200421201705 ◽

2020 ◽

Vol 10 ◽

Author(s):

Samad Nazemi ◽

Faranak Jafari ◽

Bahareh Amin ◽

Omid Gholami ◽

Marzieh Kafami ◽

...

Keyword(s):

Spinal Cord ◽

Neuropathic Pain ◽

Sciatic Nerve ◽

Rat Model ◽

Chronic Constriction Injury ◽

Antinociceptive Activity ◽

Necrosis Factor Alpha ◽

Tnf Α ◽

Male Wistar Rats ◽

Anti Inflammatory

Objective: Although morphine is among of the first line medicines for treatment of neuropathic pain, evidence has shown that the morphine efficacy gradually decreases and a tolerance can occur. Rregarding the many reports concerning the antinociceptive and anti-inflammatory properties of umbelliprenin (UMB), this study aimed to investigate the effect of UMB on antinociceptive activity of morphine in a rat model of neuropathic pain induced by chronic constriction injury (CCI) of the sciatic nerve. Methods: Twenty-four male Wistar rats were randomly divided into sham, CCI and CCI + UMB100 (100 μg UMB per rat) groups. UMB was intrathecally administered once daily for four consecutive days (from the day before surgery until the day 2 after surgery). All the animals received a single dose of morphine (5 mg/kg, s.c.) on day 14. To evaluate the effect of UMB on antinociceptive activity of morphine, allodynia and hyperalgesia were measured using the von-Frey and hot plate tests, before and 30 min after morphine injection, and the Percentage of Maximum Possible Effect (%MPE) was calculated. In addition, the expression and concentration of tumor necrosis factor-alpha (TNF-α), as a proinflammatory cytokine, was measured in the spinal cord using quantitative real-time PCR (RT-PCR) and ELISA, respectively. Key Findings: UMB significantly enhanced anti-allodynic and anti-hyperalgesic effects of morphine in the neuropathic animals. Moreover, UMB considerably downregulated TNF-α expression in the spinal cord of the animals. Conclusion: UMB can enhance antinociceptive effects of morphine, and this action may be due in part to its anti-inflammatory property.

Download Full-text

Intrathecal injection of siRNA targeting Toll-like receptor 4 reduces neuropathic pain in rat model of chronic constriction injury

Academic Journal of Second Military Medical University ◽

10.3724/sp.j.1008.2011.00377 ◽

2011 ◽

Vol 31 (4) ◽

pp. 377-381

Author(s):

Fei-xiang WU ◽

Xue-rong MIAO ◽

Xue-wu XU ◽

Yu-ming SUN ◽

Wei-feng YU

Keyword(s):

Neuropathic Pain ◽

Rat Model ◽

Chronic Constriction Injury ◽

Intrathecal Injection ◽

Toll Like Receptor ◽

Toll Like Receptor 4

Download Full-text

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

Clinical Phytoscience ◽

10.1186/s40816-021-00263-7 ◽

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.

Download Full-text