Evaluation of the GABAA Receptor Expression and the Effects of Muscimol on the Activity of Wide Dynamic Range Neurons Following Chronic Constriction Injury of Sciatic Nerve in Rats
Introduction: The modality of γ-aminobutyric acid type a receptors (GABAA) controls dorsal horn neuronal excitability and inhibits sensory information. This study aimed to investigate the expression of the GABAA receptor and the effects of its agonist muscimol on Wide Dynamic Range (WDR) neuronal ac...
| Main Authors: | , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Iran University of Medical Sciences
2021-09-01
|
| Series: | Basic and Clinical Neuroscience |
| Subjects: | |
| Online Access: | http://bcn.iums.ac.ir/article-1-1496-en.html |
| _version_ | 1827331633498292224 |
|---|---|
| author | Mehdi Sadeghi Homa Manaheji Jalal Zaringhalam Abbas Haghparast Samad Nazemi Zahra Bahari Seyed Mohammad Noorbakhsh |
| author_facet | Mehdi Sadeghi Homa Manaheji Jalal Zaringhalam Abbas Haghparast Samad Nazemi Zahra Bahari Seyed Mohammad Noorbakhsh |
| author_sort | Mehdi Sadeghi |
| collection | DOAJ |
| description | Introduction: The modality of γ-aminobutyric acid type a receptors (GABAA) controls dorsal horn neuronal excitability and inhibits sensory information. This study aimed to investigate the expression of the 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 to induce CCI neuropathy. Fourteen days after surgery, muscimol (0.5, 1, and 2 mg/kg IP) was injected. Then, the behavioral tests were performed. After that, the animals were killed, 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 14 days after CCI.
Results: The outcomes indicated the development of thermal hyperalgesia and mechanical allodynia after neuropathy; nonetheless, the expression of the GABAA receptor α1 subunit did not change significantly. Moreover, the evoked responses of the WDR neurons to electrical, mechanical, and thermal stimuli increased considerably. Fourteen days after CCI, muscimol administration decreased thermal hyperalgesia, mechanical allodynia, and hyper-responsiveness of the WDR neurons in CCI rats.
Conclusion: The modulation of the spinal GABAA receptors after nerve injury can offer further insights to design new therapeutic agents to reduce neuropathic pain symptoms. |
| first_indexed | 2024-03-07T16:42:02Z |
| format | Article |
| id | doaj.art-20ba2166508e4c8cb349cffd647c4785 |
| institution | Directory Open Access Journal |
| issn | 2008-126X 2228-7442 |
| language | English |
| last_indexed | 2024-03-07T16:42:02Z |
| publishDate | 2021-09-01 |
| publisher | Iran University of Medical Sciences |
| record_format | Article |
| series | Basic and Clinical Neuroscience |
| spelling | doaj.art-20ba2166508e4c8cb349cffd647c47852024-03-03T07:47:26ZengIran University of Medical SciencesBasic and Clinical Neuroscience2008-126X2228-74422021-09-01125651666Evaluation of the GABAA Receptor Expression and the Effects of Muscimol on the Activity of Wide Dynamic Range Neurons Following Chronic Constriction Injury of Sciatic Nerve in RatsMehdi Sadeghi0Homa Manaheji1Jalal Zaringhalam2Abbas Haghparast3Samad Nazemi4Zahra Bahari5Seyed Mohammad Noorbakhsh6 Department of Physiology, School of Medicine, Bushehr University of Medical Sciences, Bushehr, Iran. Neurophysiology Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran. Department of Physiology, Faculty of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran. Neuroscience Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran. Department of Physiology, School of Medicine, Sabzevar University of Medical Sciences, Sabzevar, Iran. Department of Physiology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran. Science Beam Institute, Tehran, Iran. Introduction: The modality of γ-aminobutyric acid type a receptors (GABAA) controls dorsal horn neuronal excitability and inhibits sensory information. This study aimed to investigate the expression of the 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 to induce CCI neuropathy. Fourteen days after surgery, muscimol (0.5, 1, and 2 mg/kg IP) was injected. Then, the behavioral tests were performed. After that, the animals were killed, 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 14 days after CCI. Results: The outcomes indicated the development of thermal hyperalgesia and mechanical allodynia after neuropathy; nonetheless, the expression of the GABAA receptor α1 subunit did not change significantly. Moreover, the evoked responses of the WDR neurons to electrical, mechanical, and thermal stimuli increased considerably. Fourteen days after CCI, muscimol administration decreased thermal hyperalgesia, mechanical allodynia, and hyper-responsiveness of the WDR neurons in CCI rats. Conclusion: The modulation of the spinal GABAA receptors after nerve injury can offer further insights to design new therapeutic agents to reduce neuropathic pain symptoms.http://bcn.iums.ac.ir/article-1-1496-en.htmlneuropathic painchronic constriction injury (cci)γ-aminobutyric acid type a (gabaa) receptormuscimolwide dynamic range (wdr) neurons |
| spellingShingle | Mehdi Sadeghi Homa Manaheji Jalal Zaringhalam Abbas Haghparast Samad Nazemi Zahra Bahari Seyed Mohammad Noorbakhsh Evaluation of the GABAA Receptor Expression and the Effects of Muscimol on the Activity of Wide Dynamic Range Neurons Following Chronic Constriction Injury of Sciatic Nerve in Rats Basic and Clinical Neuroscience neuropathic pain chronic constriction injury (cci) γ-aminobutyric acid type a (gabaa) receptor muscimol wide dynamic range (wdr) neurons |
| title | Evaluation of the GABAA Receptor Expression and the Effects of Muscimol on the Activity of Wide Dynamic Range Neurons Following Chronic Constriction Injury of Sciatic Nerve in Rats |
| title_full | Evaluation of the GABAA Receptor Expression and the Effects of Muscimol on the Activity of Wide Dynamic Range Neurons Following Chronic Constriction Injury of Sciatic Nerve in Rats |
| title_fullStr | Evaluation of the GABAA Receptor Expression and the Effects of Muscimol on the Activity of Wide Dynamic Range Neurons Following Chronic Constriction Injury of Sciatic Nerve in Rats |
| title_full_unstemmed | Evaluation of the GABAA Receptor Expression and the Effects of Muscimol on the Activity of Wide Dynamic Range Neurons Following Chronic Constriction Injury of Sciatic Nerve in Rats |
| title_short | Evaluation of the GABAA Receptor Expression and the Effects of Muscimol on the Activity of Wide Dynamic Range Neurons Following Chronic Constriction Injury of Sciatic Nerve in Rats |
| title_sort | evaluation of the gabaa receptor expression and the effects of muscimol on the activity of wide dynamic range neurons following chronic constriction injury of sciatic nerve in rats |
| topic | neuropathic pain chronic constriction injury (cci) γ-aminobutyric acid type a (gabaa) receptor muscimol wide dynamic range (wdr) neurons |
| url | http://bcn.iums.ac.ir/article-1-1496-en.html |
| work_keys_str_mv | AT mehdisadeghi evaluationofthegabaareceptorexpressionandtheeffectsofmuscimolontheactivityofwidedynamicrangeneuronsfollowingchronicconstrictioninjuryofsciaticnerveinrats AT homamanaheji evaluationofthegabaareceptorexpressionandtheeffectsofmuscimolontheactivityofwidedynamicrangeneuronsfollowingchronicconstrictioninjuryofsciaticnerveinrats AT jalalzaringhalam evaluationofthegabaareceptorexpressionandtheeffectsofmuscimolontheactivityofwidedynamicrangeneuronsfollowingchronicconstrictioninjuryofsciaticnerveinrats AT abbashaghparast evaluationofthegabaareceptorexpressionandtheeffectsofmuscimolontheactivityofwidedynamicrangeneuronsfollowingchronicconstrictioninjuryofsciaticnerveinrats AT samadnazemi evaluationofthegabaareceptorexpressionandtheeffectsofmuscimolontheactivityofwidedynamicrangeneuronsfollowingchronicconstrictioninjuryofsciaticnerveinrats AT zahrabahari evaluationofthegabaareceptorexpressionandtheeffectsofmuscimolontheactivityofwidedynamicrangeneuronsfollowingchronicconstrictioninjuryofsciaticnerveinrats AT seyedmohammadnoorbakhsh evaluationofthegabaareceptorexpressionandtheeffectsofmuscimolontheactivityofwidedynamicrangeneuronsfollowingchronicconstrictioninjuryofsciaticnerveinrats |