The increased release of amino acid neurotransmitters of the primary somatosensory cortical area in rats contributes to remifentanil-induced hyperalgesia and its inhibition by lidocaine.

Abstract

BackgroundStudies have confirmed that activation of the neurons of primary somatosensory cortex (S1) is involved in the process of remifentanil (Remi)-induced hyperalgesia (RIH), which can be suppressed by lidocaine (Lido). A total intravenous anesthesia model of rats mimicking clinical Remi-based anesthesia was set up to explore the release of amino acid neurotransmitters of S1 cortex in RIH and its inhibition by Lido in this study.Materials and methodsSprague Dawley rats were randomly divided into the following four groups: propofol (Pro), Remi, Remi combined Lido, and Lido groups. Mechanical hyperalgesia was evaluated by von Frey test; the amino acid neurotransmitters in the microdialysates of S1 area were detected by high-performance liquid chromatography (HPLC)-fluorescence, and conventional protein kinase C (cPKC)γ levels in the whole-cell lysates and membrane lipid rafts (MLRs) were determined by Western blotting.ResultsThe von Frey test showed that co-administration of Lido significantly inhibited a Remi-induced decrease in the threshold of the paw withdrawal response in Remi group at 2 h postinfusion. Meanwhile, the Remi-induced increases in both the excitatory and inhibitory amino acid releases in S1 were suppressed by co-administrating Lido within 5 h postinfusion. Western blotting showed that the increased cPKCγ level in the membrane lipid rafts (MLR) induced by Remi was also inhibited by Lido.ConclusionThe increased release of amino acid neurotransmitters and the translocation of cPKCγ in MLR suggest the activation of S1 neurons, which may be one of the mechanisms underlying RIH. Lido reduces the release of amino acid neurotransmitters in S1 neurons and the translocation of cPKCγ in MLRs after stopping Remi, which may be one of its antihyperalgesic mechanisms.