Avaliação papel do óxido nítrico na comunicação glutamatérgica entre nociceptores e células satélites de gânglios sensoriais de rato

Abstract

Introduction: Interactions between satellite glial cells (SGCs) and nociceptive neurons in dorsal root ganglia (DRG) affect neuronal excitability during pain signal transmission. Previous studies have shown that neurons release glutamate, which activates CGSs. These, in turn, interfere with neural activation by promoting membrane depolarization. Objectives: To evaluate the role of nitric oxide (NO) and L-NAME in the depolarization of primary afferent neurons resulting from the activation of NMDA receptors in glial satellite cells. Methods: The effect of a nitric oxide donor, sodium nitroprusside (NPS, 10 µM, 100 µM and 1 mM) was evaluated, as well as the effect of L-NAME (100 µM), a non-specific inhibitor of the enzyme nitric oxide synthetase. Changes in resting potential were assessed by confocal microscopy using the fluorescent indicator DiBAC4(3), whose movement on the membrane due to depolarization results in increased fluorescence. The effect of blocking nitric oxide synthase in the dorsal root ganglia was tested through the intrathecal injection of L-NAME using behavioral tests in which the participation of glutamate in the dorsal root ganglia was verified in earlier studies. The behavioral tests were the capsaicin test and mechanical hyperalgesia induced by the injection of carrageenan, both in rat paws. Results: The administration of the NO donor at a concentration of 1 mM induced a significant neuronal depolarization (0.18 ± 0.02) when compared to the vehicle (-0.03 ± 0.005), while there was no effect with the lower concentrations. The Administration of the NOS inhibitor inhibited NMDA-induced neuronal depolarization (-0.07 ± 0.03) when compared to the NMDA group (0.15 ± 0.04). It was possible to observe a significant increase in fluorescence when capsaicin was added to the medium with L-NAME (0.60 ± 0.06) compared to the vehicle (-0.02 ± 0.03). In behavioral tests, no effect was observed at any of the L-NAME concentrations compared to vehicle administration. Conclusions: Results indicate that NO can depolarizate nociceptive neurons, which corroborates the hypothesis that this mediator participates in the communication between neurons and SGCs. NO also appears to be involved in glutamatergic communication in DRG.