Role of mammalian target of rapamycin in synaptic plasticity of entorhinal area-hippocampal formation in rats with inflammatory pain

Abstract

Objective To evaluate the role of mammalian target of rapamycin(mTOR) in the synaptic plasticity of entorhinal area-hippocampal formation in rats with inflammatory pain. Methods Twenty-four healthy adult male Sprague-Dawley rats, weighing 180-240 g, were divided into 4 groups(n=6 each) by using a random number table method: control group(group C), inflammatory pain group(group IP), dimethyl sulfoxide(DMSO) group and mTOR inhibitor rapamycin group(group R). Inflammatory pain model was established by subcutaneous injection of 50 μl bee venom into the plantar surface of the left hindpaw. The equal volume of normal saline was subcutaneously injected into the plantar surface of the left hindpaw in group C. In group DMSO, 2% DMSO was administered by intragastric gavage for 3 days, 1 ml per day, and the inflammatory pain model was established at 1 h after administration on 3rd day. In group R, rapamycin was administered by intragastric gavage for 3 days, 1 ml per day, and the inflammatory pain model was established at 1 h after administration on 3rd day. Mechanical paw withdrawal threshold(MWT) and thermal paw withdrawal latency(TWL) were measured at 2 h after establishing the model. The rats were sacrificed after measurement of the pain threshold, and hippocampi were removed to prepare hippocampal slices. Hippocampal CA1 region and dentate gyrus(DG region) were located with an inverted microscope. Planar microelectrode array technique was used to record the number of channels and the standardized amplitude of evoked effective field excitatory postsynaptic potentials(fEPSPs)(fEPSPs amplitude>20% of the baseline value) at different stimulus intensities. Results Compared with group C, MWT was significantly decreased, TWL was shortened, the number of effective fEPSP channels at different stimulus intensities was increased, and the amplitude of standardized fEPSPs in hippocampal DG and CA1 regions was increased in group IP(P 0.05). Compared with group IP, MWT was significantly increased, TWL was prolonged, the number of effective fEPSP channels at different stimulus intensities was decreased, and the amplitude of standardized fEPSPs in hippocampal DG and CA1 regions was decreased in group R(P 0.05). Conclusion mTOR is involved in the changes in the synaptic plasticity of entorhinal area-hippocampal formation in rats with inflammatory pain. Key words: Receptor-interacting protein serine-threonine kinases; Hippocampus; Entorhinal cortex; Pain; Inflammation; Neuronal plasticity