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

Abstract

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.