scholarly journals Evaluation of the GABAA Receptor Expression and the Effects of Muscimol on the Activity of Wide Dynamic Range Neurons Following Chronic Constriction Injury of the Sciatic Nerve in Rats

2021 ◽  
Author(s):  
Mehdi Sadeghi ◽  
Keyword(s):  
Neuropathic Pain ◽  
Gabaa Receptor ◽  
Mechanical Allodynia ◽  
Chronic Constriction Injury ◽  
Dynamic Range ◽  
Thermal Hyperalgesia ◽  
Receptor Expression ◽  
Wide Dynamic Range ◽  
Wdr Neurons ◽  
Α1 Subunit

Introduction: The modality of γ-aminobutyric acid receptors (GABAA) in control of dorsal horn neuronal excitability and inhibition of sensory information is ambiguous. The aim of the present study was to investigate the expression of GABAA receptor and the effects of its agonist muscimol on wide dynamic range (WDR) neuronal activity in the chronic constriction injury (CCI) model of neuropathic pain. Methods: Adult male Wistar rats weighing 200 to 250 g were used for the induction of CCI neuropathy. 14 days after surgery, muscimol (0.5, 1, and 2 mg/kg i.p.) was injected. Then, the behavioral tests were performed. Thereafter, the animals were sacrificed, and the lumbar segments of the spinal cords were collected for Western blot analysis of the GABAA receptor α1 subunit expression. The electrophysiological properties of WDR neurons were studied by single unit recordings in separate groups on the 14th day after CCI. Results: The outcomes indicated the development of thermal hyperalgesia and mechanical allodynia after neuropathy; nonetheless, the expression of GABAA receptor α1 subunit did not change significantly. Moreover, the evoked responses of the WDR neurons to electrical, mechanical, and thermal stimuli were significantly increased. 14 days after CCI, muscimol administration decreased thermal hyperalgesia, mechanical allodynia, and hyper-responsiveness of the WDR neurons in CCI rats. Conclusion: It confirms that the modulation of the spinal GABAA receptors after nerve injury can offer further insights to design new therapeutic agents in order to reduce the neuropathic pain symptoms.

scholarly journals Evaluation of the GABAA Receptor Expression and the Effects of Muscimol on the Activity of Wide Dynamic Range Neurons Following Chronic Constriction Injury of the Sciatic Nerve in Rats

2021 ◽  
Author(s):  
Mehdi Sadeghi ◽  
◽  
Homa Manaheji ◽  
Jalal Zaringhalam ◽  
Abbas Haghparast ◽  
...  
Keyword(s):  
Neuropathic Pain ◽  
Gabaa Receptor ◽  
Mechanical Allodynia ◽  
Chronic Constriction Injury ◽  
Dynamic Range ◽  
Thermal Hyperalgesia ◽  
Receptor Expression ◽  
Wide Dynamic Range ◽  
Wdr Neurons ◽  
Α1 Subunit

Introduction: The modality of γ-aminobutyric acid receptors (GABAA) in control of dorsal horn neuronal excitability and inhibition of sensory information is ambiguous. The aim of the present study was to investigate the expression of GABAA receptor and the effects of its agonist muscimol on wide dynamic range (WDR) neuronal activity in the chronic constriction injury (CCI) model of neuropathic pain. Methods: Adult male Wistar rats weighing 200 to 250 g were used for the induction of CCI neuropathy. 14 days after surgery, muscimol (0.5, 1, and 2 mg/kg i.p.) was injected. Then, the behavioral tests were performed. Thereafter, the animals were sacrificed, and the lumbar segments of the spinal cords were collected for Western blot analysis of the GABAA receptor α1 subunit expression. The electrophysiological properties of WDR neurons were studied by single unit recordings in separate groups on the 14th day after CCI. Results: The outcomes indicated the development of thermal hyperalgesia and mechanical allodynia after neuropathy; nonetheless, the expression of GABAA receptor α1 subunit did not change significantly. Moreover, the evoked responses of the WDR neurons to electrical, mechanical, and thermal stimuli were significantly increased. 14 days after CCI, muscimol administration decreased thermal hyperalgesia, mechanical allodynia, and hyper-responsiveness of the WDR neurons in CCI rats. Conclusion: It confirms that the modulation of the spinal GABAA receptors after nerve injury can offer further insights to design new therapeutic agents in order to reduce the neuropathic pain symptoms.

scholarly journals Long-term Application of Glycine Transporter Inhibitors Acts Antineuropathic and Modulates Spinal N-methyl-d-aspartate Receptor Subunit NR-1 Expression in Rats

2014 ◽  
Vol 121 (1) ◽  
pp. 160-169 ◽  
Author(s):  
Franziska Barthel ◽  
Andrea Urban ◽  
Lukas Schlösser ◽  
Volker Eulenburg ◽  
Robert Werdehausen ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Neuropathic Pain ◽  
Side Effects ◽  
Mechanical Allodynia ◽  
Chronic Constriction Injury ◽  
Thermal Hyperalgesia ◽  
Receptor Expression ◽  
Dependent Manner ◽  
Receptor Subunit ◽  
Aspartate Receptor

Abstract Background: Dysfunction of spinal glycinergic neurotransmission is a major pathogenetic factor in neuropathic pain. The synaptic glycine concentration is controlled by the two glycine transporters (GlyT) 1 and 2. GlyT inhibitors act antinociceptive in various animal pain models when applied as bolus. Yet, in some studies, severe neuromotor side effects were reported. The aim of the current study was to elucidate whether continuous inhibition of GlyT ameliorates neuropathic pain without side effects and whether protein expression of GlyT1, GlyT2, or N-methyl-d-aspartate receptor subunit NR-1 in the spinal cord is affected. Methods: In the chronic constriction injury model of neuropathic pain, male Wistar rats received specific GlyT1 and GlyT2 inhibitors (ALX5407 and ALX1393; Sigma-Aldrich®, St. Louis, MO) or vehicle for 14 days via subcutaneous osmotic infusion pumps (n = 6). Mechanical allodynia and thermal hyperalgesia were assessed before, after chronic constriction injury, and every 2 days during substance application. At the end of behavioral assessment, the expression of GlyT1, GlyT2, and NR-1 in the spinal cord was determined by Western blot analysis. Results: Both ALX5407 and ALX1393 ameliorated thermal hyperalgesia and mechanical allodynia in a time- and dose-dependent manner. Respiratory or neuromotor side effects were not observed. NR-1 expression in the ipsilateral spinal cord was significantly reduced by ALX5407, but not by ALX1393. The expression of GlyT1 and GlyT2 remained unchanged. Conclusions: Continuous systemic inhibition of GlyT significantly ameliorates neuropathic pain in rats. Thus, GlyT represent promising targets in pain research. Modulation of N-methyl-d-aspartate receptor expression might represent a novel mechanism for the antinociceptive action of GyT1 inhibitors.

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.

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.

scholarly journals Tongluo Zhitong Prescription Alleviates Allodynia, Hyperalgesia, and Dyskinesia in the Chronic Constriction Injury Model of Rats

2017 ◽  
Vol 2017 ◽  
pp. 1-6 ◽  
Author(s):  
Zhiyong Wang ◽  
Jianwei Wang ◽  
Lihua Qin ◽  
Weiguang Zhang
Keyword(s):  
Neuropathic Pain ◽  
Mechanical Allodynia ◽  
Chronic Constriction Injury ◽  
Catgut Suture ◽  
Cold Allodynia ◽  
Injury Model ◽  
Neuropathic Pain Model ◽  
Gait Function ◽  
Chronic Constriction Injury Model ◽  
Heat Hyperalgesia

Neuropathic pain is common in clinical practice. Exploration of new drug therapeutics has always been carried out for more satisfactory effects and fewer side-effects. In the present study, we aimed to investigate effects of Tongluo Zhitong Prescription (TZP), a compounded Chinese medicine description, on neuropathic pain model of rats with chronic constriction injury (CCI). The CCI model was established by loosely ligating sciatic nerve with catgut suture, proximal to its trifurcation. The static and dynamic allodynia, heat hyperalgesia, mechanical allodynia, cold allodynia, and gait were assessed. Our results showed that TZP alleviated CCI-induced static and dynamic allodynia, suppressed heat hyperalgesia and cold and mechanical allodynia, and improved gait function. These results suggest that TZP could alleviate neuropathic pain. Further experiments are needed to explore its mechanisms.

Activation of Spinal Wide Dynamic Range Neurons by Intracutaneous Microinjection of Nicotine

1999 ◽  
Vol 82 (6) ◽  
pp. 3046-3055 ◽  
Author(s):  
Steven L. Jinks ◽  
E. Carstens
Keyword(s):  
Nicotinic Acetylcholine Receptors ◽  
Acetylcholine Receptors ◽  
Dynamic Range ◽  
Receptive Fields ◽  
Threshold Region ◽  
Partial Recovery ◽  
Evoked Responses ◽  
Wide Dynamic Range ◽  
Analgesic Effects ◽  
Wdr Neurons

Nicotine evokes pain in the skin and oral mucosa and excites a subpopulation of cutaneous nociceptors, but little is known about the central transmission of chemogenic pain. We have investigated the responses of lumbar spinal wide dynamic range (WDR)-type dorsal horn neurons to intracutaneous (ic) microinjection of nicotine in pentobarbital-anesthetized rats. Nearly all (97%) units responded to nicotine microinjected ic (1 μl) into the low-threshold region of the hind-paw mechanosensitive receptive field in a concentration-related manner (0.01–10%). Responses to repeated injections of 10% nicotine exhibited tachyphylaxis at 5-, 10-, and 15-min interstimulus intervals. Significant tachyphylaxis was not seen with 1% nicotine. All nicotine-responsive units tested ( n = 30) also responded to ic histamine (1 μl, 3%) and did not exhibit tachyphylaxis to repeated histamine. However, there was significant cross-tachyphylaxis of nicotine to histamine. Thus 5 min after ic nicotine, histamine-evoked responses were attenuated significantly compared with the initial histamine-evoked response prior to nicotine, with partial recovery over the ensuing 15 min. Neuronal excitation by ic nicotine was not mediated by histamine H1 receptors because ic injection of the H1 receptor antagonist, cetirizine, had no effect on ic nicotine-evoked responses, whereas it significantly attenuated ic histamine-evoked responses in the same neurons. The lowest-threshold portion of cutaneous receptive fields showed a significant expansion in area at 20 min after ic nicotine 10%, indicative of sensitization. Responses to 1% nicotine were significantly reduced after ic injection of the nicotinic antagonist, mecamylamine (0.1% ic), with no recovery over the ensuing 40–60 min. These data indicate that nicotine ic excites spinal WDR neurons, partly via neuronal nicotinic acetylcholine receptors that are presumably expressed in cutaneous nociceptor terminals. Repeated injections of high concentrations of nicotine led to tachyphylaxis and cross-tachyphylaxis with histamine, possibly relevant to peripheral analgesic effects of nicotine.

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 Analgesic Effect of Moxibustion with Different Temperature on Inflammatory and Neuropathic Pain Mice: A Comparative Study

2017 ◽  
Vol 2017 ◽  
pp. 1-8 ◽  
Author(s):  
Wei Zhou ◽  
Ruxue Lei ◽  
Chuanyi Zuo ◽  
Yunqing Yue ◽  
Qin Luo ◽  
...  
Keyword(s):  
Neuropathic Pain ◽  
Inflammatory Pain ◽  
Analgesic Effect ◽  
Mechanical Allodynia ◽  
Thermal Hyperalgesia ◽  
Spared Nerve Injury ◽  
Chronic Neuropathic Pain ◽  
Chronic Inflammatory Pain ◽  
Significant Difference ◽  
Different Temperatures

The aim of this study was to determine whether variation of temperature during moxibustion would generate division of analgesic effect. The moxibustion with different temperatures (37°C, 42°C, 47°C, and 52°C) was applied to ST36 acupoint for 30 minutes in chronic inflammatory or neuropathic pain mice. The analgesic effect was evaluated by thermal hyperalgesia test in chronic inflammatory pain and by mechanical allodynia in neuropathic pain, respectively. The results indicated that interventions of moxibustion with different temperature caused different analgesic effect on either chronic inflammatory induced by injection of complete Freund’s adjuvant (CFA) or neuropathic pain induced by spared nerve injury (SNI). In chronic inflammatory pain, different moxibustion temperature generated different intensity of analgesic effect: the higher the better. In chronic neuropathic pain, stronger analgesic effect was found in moxibustion with temperature 47°C or 52°C other than 37°C and 42°C. However, there is no significant difference displayed between moxibustion temperatures 47°C and 52°C or 37°C and 42°C. It implies that the temperature should be taken into account for moxibustion treatment to chronic inflammatory or neuropathic pain.

Sign in / Sign up

Export Citation Format

Share Document