Volume 12, Issue 5 (September & October 2021)
BCN 2021, 12(5): 651-666 |
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Sadeghi M, Manaheji H, Zaringhalam J, Haghparast A, Nazemi S, Bahari Z et al . 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. BCN 2021; 12 (5) :651-666
URL: http://bcn.iums.ac.ir/article-1-1496-en.html
URL: http://bcn.iums.ac.ir/article-1-1496-en.html
Mehdi Sadeghi1 
, Homa Manaheji * 2, Jalal Zaringhalam3 , Abbas Haghparast4 , Samad Nazemi5 , Zahra Bahari6 , Seyed Mohammad Noorbakhsh7
, Homa Manaheji * 2, Jalal Zaringhalam3 , Abbas Haghparast4 , Samad Nazemi5 , Zahra Bahari6 , Seyed Mohammad Noorbakhsh7
1- Department of Physiology, School of Medicine, Bushehr University of Medical Sciences, Bushehr, Iran.
2- Neurophysiology Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
3- Department of Physiology, Faculty of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
4- Neuroscience Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
5- Department of Physiology, School of Medicine, Sabzevar University of Medical Sciences, Sabzevar, Iran.
6- Department of Physiology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
7- Science Beam Institute, Tehran, Iran.
2- Neurophysiology Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
3- Department of Physiology, Faculty of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
4- Neuroscience Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
5- Department of Physiology, School of Medicine, Sabzevar University of Medical Sciences, Sabzevar, Iran.
6- Department of Physiology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
7- Science Beam Institute, Tehran, Iran.
Abstract:
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.
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.
Keywords: Neuropathic pain, Chronic Constriction Injury (CCI), γ-Aminobutyric acid type A (GABAA) receptor, Muscimol, Wide Dynamic Range (WDR) neurons
Type of Study: Original |
Subject:
Behavioral Neuroscience
Received: 2019/05/9 | Accepted: 2020/08/5 | Published: 2021/09/1
Received: 2019/05/9 | Accepted: 2020/08/5 | Published: 2021/09/1
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