GABAA receptor plasticity in neuropathic pain: pain and memory effects in adult female rats

Background Neuropathic pain has been shown to increase excitability of neurons. This indicates altered inhibitory mechanism of the nervous system. Objective This work was aimed to assess GABAA receptors plasticity in the brain and spinal cord. Materials and methods Fifteen adult female rats were used. Ten animals have their sciatic nerve ligated with no treatment (LIG), and with diazepam treatment for 14 days (LIG+GABA) and the other five were used as the sham group. Pain was assessed using a hot plate and formalin test, while the spatial memory was assessed using Y-maze. At the end of the treatment, the animals were euthanized and fixed using the transcardial perfusion fixation method. The spinal cord, cingulate cortex, and the hippocampus were serially sectioned and stained for GABAA receptor immunohistochemically. Quantification was done using ImageJ software. Data were analyzed using oneway analysis of variance and Newman Tukey post-hoc test significant level was set at P less than 0.05. Results A low level of pain was observed in LIG and LIG+GABA animals on both formalin and hot plate test compared with the control. Memory impairment was found only in the LIG+GABA group. Stereology counting showed that GABAA receptors reduced in the dentate gyrus of the hippocampus of LIG-treated animals which was reversed in LIG+GABA, but in the cingulate cortex, GABAA receptors were increased in LIG animals and LIG+GABA more than the control while the spinal cord shows no significant difference. Conclusion GABAA agonist treatment did not alleviate the symptoms of neuropathic pain due to GABA signaling changing to excitatory in nature