Modification of the Activation System of NaV1.8 Channels Determines the Molecular Mechanism of the Antinociceptive Response

Resumo

Using the sensory neuron membrane model we have demonstrated that the ectopic burst activity that arises in response to the pronociceptive stimulus is determined by the dynamics of the system with one slow variable describing inactivation of slow sodium Na_V1.8 channels. This activity can be suppressed exclusively by modification of the activation gating system of these channels under the influence of comenic acid, which is the active substance of the novel non-opioid analgesic anoceptin. It has been shown that when the potassium channels are blocked, the burst activity of the first type is suppressed after modification of Na_V1.8 channels caused by comenic acid at positive and negative conductance, while the burst activity of the second type is kept at the same level, but the range of stimuli within which this activity may occur significantly decreases.