scholarly journals A Pusher and a Clip Applied to Hind Paws Under Isoflurane Sedation to Evaluate Neuropathic Pain in a CCI Model

2021 ◽  
Vol 11 (6) ◽  
Author(s):  
Reiko Nobuhara ◽  
Akihiro Ito ◽  
Masafumi Nakagawa ◽  
Tatsunori Ikemoto ◽  
Kimimasa Narita ◽  
...  
Keyword(s):  
Neuropathic Pain ◽  
Chronic Constriction Injury ◽  
Prairie Voles ◽  
Nociceptive Behavior ◽  
Human Contact ◽  
Rodent Behavior ◽  
Mechanical Threshold ◽  
Consistent Manner ◽  
Cci Model ◽  
Mechanical Thresholds

: Rodent behavior assessments have been developed to evaluate pain. However, their fidgety activity and reactivity to human contact make it hard to activate animals in a consistent manner and get uniform and trustworthy responses. The present study was performed on prairie voles (aged 8 weeks). Sham (7 male prairie voles) and chronic constriction injury (CCI) (8 male prairie voles) rodents were investigated before surgery and four and seven days later. Each animal was assessed for nociceptive behavior. Pressure and mechanical threshold tests were conducted by the application of three different pushers to the center of hind paws and arterial clips to the toes while sedated with isoflurane. The CCI affected right lower extremity prominently increased nociceptive behavior scores four and seven days after the experiment, and the CCI affected right hind paw prominently decreased pressure and mechanical threshold tests four and seven days after the experiment . The pressure and mechanical thresholds were relevant to the scorings of nociceptive behavior in CCI model animals.

scholarly journals Alterations in mouse spinal cord and sciatic nerve microRNAs after the chronic constriction injury (CCI) model of neuropathic pain

2020 ◽  
Vol 731 ◽  
pp. 135029
Author(s):  
Jenny L. Wilkerson ◽  
Jinmai Jiang ◽  
Jasmine S. Felix ◽  
Julie K. Bray ◽  
Lais da Silva ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Neuropathic Pain ◽  
Sciatic Nerve ◽  
Chronic Constriction Injury ◽  
Mouse Spinal Cord ◽  
Cci Model

scholarly journals An Adapted Chronic Constriction Injury of the Sciatic Nerve Produces Sensory, Affective, and Cognitive Impairments: A Peripheral Mononeuropathy Model for the Study of Comorbid Neuropsychiatric Disorders Associated with Neuropathic Pain in Rats

Pain Medicine ◽  
2020 ◽  
Author(s):  
Priscila Medeiros ◽  
Ieda Regina dos Santos ◽  
Ivair Matias Júnior ◽  
Enza Palazzo ◽  
José Aparecido da Silva ◽  
...  
Keyword(s):  
Neuropathic Pain ◽  
Sciatic Nerve ◽  
Mechanical Allodynia ◽  
Chronic Constriction Injury ◽  
Anxiety And Depression ◽  
Novel Object Recognition ◽  
Walking Test ◽  
Cci Model ◽  
Underlying Mechanisms ◽  
Motor Alterations

Abstract Background Chronic constriction injury (CCI) is a model of neuropathic pain induced by four loose ligatures around the sciatic nerve. This work aimed to investigate the sensory, affective, cognitive, and motor changes induced by an adaptation of the CCI model by applying a single ligature around the sciatic nerve. Methods Mechanical allodynia was measured from day 1 to day 28 postsurgery by the von Frey test. The beam walking test (BWT) was conducted weekly until 28 days after surgery. Anxiety- and depression-like behaviors, and cognitive performance were assessed through the open field (OF), forced swimming (FS), and novel object recognition (NOR) tests, respectively, 21 days after surgery. Results The two CCI models, both Bennett and Xie’s model (four ligatures of the sciatic nerve) and a modification of it (one ligature), induced mechanical allodynia, increased immobility in the FS, and reduced recognition index in the NOR. The exploratory behavior and time spent in the central part of the arena decreased, while the defensive behavior increased in the OF. The animals subjected to the two CCI models showed motor alterations in the BWT; however, autotomy was observed only in the group with four ligatures and not in the group with a single ligature. Conclusions Overall these results demonstrate that our adapted CCI model, using a single ligature around the sciatic nerve, induces sensory, affective, cognitive, and motor alterations comparable to the CCI model with four ligatures without generating autotomy. This adaptation to the CCI model may therefore represent an appropriate and more easily performed model for inducing neuropathic pain and study underlying mechanisms and effective treatments.

scholarly journals Vitexin alleviates neuropathic pain in a mouse chronic constriction injury model by inactivation of NF-κB

2020 ◽  
Vol 19 (5) ◽  
pp. 989-994
Author(s):  
Wentong Xu ◽  
Xueli Zhu ◽  
Gonghao Zhan ◽  
Liangyu Sheng ◽  
Yanwei Chen
Keyword(s):  
Neuropathic Pain ◽  
Inflammatory Cytokines ◽  
Chronic Constriction Injury ◽  
Enzyme Linked Immunosorbent Assay ◽  
Mrna Levels ◽  
Mechanical Hypersensitivity ◽  
Withdrawal Threshold ◽  
Before And After ◽  
Cci Model ◽  
Pro Inflammatory Cytokines

Purpose: To investigate the therapeutic effect of vitexin on neuropathic pain (NP) in a mouse model of chronic constriction injury (CCI).Methods: The CCI model was established by four chronic ligatures in the sciatic nerve. Vitexin was intraperitoneally administered (10 mg/kg, once daily) for 21 days. Mechanical withdrawal threshold (MWT) and paw withdrawal latency (PWL) were determined before and after the establishment of CCI model. The spinal cords were collected to measure mRNA levels by reverse-transcriptase polymerase chain reaction (RT-PCR) enzyme-linked immunosorbent assay (ELISA). Western blot was used to examine protein expression levels.Results: Vitexin reversed the CCI-induced reduction in MWT and PWL values, indicating that it lowered mechanical hypersensitivity response and hyperalgesia caused thermal stimulation (p < 0.05). The elevated levels of IL-6, IL-1β, and TNFα observed in CCI-treated mice were also inhibited by vitexin, suggesting that it suppressed pro-inflammatory cytokines. Moreover, vitexin attenuated CCI-induced activation of NF-κB signaling in CCI-treated mice (p < 0.05).Conclusion: Vitexin alleviates NP by inhibiting pro-inflammatory cytokines and NF-κB signaling in CCItreated mice. Thus, it is a potential target for NP treatment. Keywords: Vitexin, Neuropathic pain, Chronic constriction injury, Mechanical hypersensitivity, Hyperalgesia, NF-κB

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 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.

scholarly journals The Effects of Dexmedetomidine Alone and in Combination with Tramadol or Amitriptyline in a Neuropathic Pain Model

2014 ◽  
Vol 2;17 (2;3) ◽  
pp. 187-195 ◽  
Author(s):  
Hanan S. M. Farghaly
Keyword(s):  
Neuropathic Pain ◽  
Side Effects ◽  
Sciatic Nerve ◽  
Mechanical Allodynia ◽  
Chronic Constriction Injury ◽  
Antinociceptive Effect ◽  
Underlying Mechanism ◽  
Mechanical Tests ◽  
Α2 Adrenoceptor ◽  
Cci Model

Background: Interactions between the sympathetic and somatic nervous system play an essential role in the pathophysiologic mechanisms of neuropathic pain. The α2-adrenoceptor agonists produce effective antinociception, but sedation is an important adverse effect. Multidrug therapy is potentially valuable to decrease side effects. Objective: The aim of the present study was to investigate the possible antinociceptive effect of dexmedetomidine, an α2-adrenoceptor agonist, and its combination with front-line treatment of neuropathic pain, i.e., amitriptyline or tramadol, in a chronic constriction injury (CCI) model of the sciatic nerve in rats. Study Design: Controlled animal study. Methods: Following unilateral ligation of the left sciatic nerve, the effect of intraperitoneal (i.p.) dexmedetomidine (5μg/kg), tramadol (5 mg/kg), and amitriptyline (30 mg/kg) on mechanical allodynia (measured by electrical von Frey apparatus) and hyperalgesia (measured by Randall and Selitto test) was studied. Results: The sham-operated rats and un-operated hind paw (right paw) press normally on the floor reproduced by a weighted pain score of 0. Behavioral and mechanical tests confirmed the development of neuropathic pain after CCI. All individual drugs and dexmedetomidine combination with either tramadol or amitriptyline were effective in reducing mechanical allodynia and hyperalgesia. Dexmedetomidine, amitriptyline, tramadol, amitriptyline+dexmedetomidine, and tramadol+dexmedetomidine combination did not produce any sedation/motor impairment (P > 0.05). Limitations: Although the combination of these drugs improved the CCI model of neuropathic pain in this study, an additional interpretation of the underlying mechanism(s) will be needed to confirm these findings. Conclusion: The combination of these drugs appears to be more effective in increasing the pain threshold after peripheral nerve injury, when compared with the administration of either of amitriptyline or tramadol alone and should be considered as a possible alternative to decrease side effects of individual drug therapy. Key words: Allodynia, amitriptyline, chronic constriction injury, dexmedetomidine, hyperalgesia, neuropathic pain, rat, tramadol

scholarly journals Hydrogen-Rich Saline Attenuated Neuropathic Pain by Reducing Oxidative Stress

2013 ◽  
Vol 40 (6) ◽  
pp. 857-863 ◽  
Author(s):  
Qianbo Chen ◽  
Ping Chen ◽  
Shuangqiong Zhou ◽  
Xiaodi Yan ◽  
John Zhang ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Spinal Cord ◽  
Neuropathic Pain ◽  
Sodium Chloride ◽  
Chronic Constriction Injury ◽  
Intrathecal Injection ◽  
Hydrogen Gas ◽  
Vehicle Group ◽  
Saline Control ◽  
Mechanical Thresholds

Background:Reactive oxygen species (ROS) are often associated with persistent pains such as neuropathic and inflammatory pain. Hydrogen gas can reduce ROS and alleviate cerebral, myocardial, and hepatic ischemia/reperfusion injuries. In the present study, we aim to investigate whether hydrogen-rich saline can reduce neuropathic pain in a rat model of chronic constriction injury (CCI).Methods:Thirty SD rats were randomly divided into three groups: sham group was administered sodium chloride by intrathecal injection (n=10); control groups underwent CCI surgery and were administered sodium chloride by intrathecal injection (n=10); vehicle group underwent CCI surgery and was administered hydrogen-rich saline by intrathecal injection (n=10). Drugs were administered in the dose of 100ul/kg once a day at 0.5 hours before and 1-7 day after CCI surgery. The mechanical thresholds were tested at one day before and 3-14 day after CCI surgery.Results:We found that hydrogen-rich saline significantly elevated the mechanical thresholds of neuropathic pain compared to vehicle (physiologic saline) control in CCI rats (p<0.05); it also decreased the levels of myeloperoxidase, maleic dialdehyde, and protein carbonyl in spinal cord by 7 days post-chronic constriction injury(p<0.05). In addition, hydrogen-rich saline also suppressed the expression of p38-mitogen-activated protein kinase (p38MAPK) and brain-derived neurotrophic factor (BDNF) in the spinal cord by 7 days post-chronic constriction injury (p<0.01, p<0.01, respectively), but had no effect on P2X4R (p>0.05), an ATP receptor.Conclusion:Intrathecal injection of hydrogen-rich saline can decrease oxidative stress and the expression of p38MAPK and BDNF that may contribute to the elevated threshold of neuropathic pain in rat CCI model.

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.

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