The 4Hz mechanical vibration-activated Na/Ca exchange as a quantum-sensitive novel target for pain therapy

The activation of Na/⁴⁰Ca exchange in reverse (R) mode leading to neuronal swelling and muscle contraction has been suggested as a mechanism for generation of pain signals. However, the activation of R Na/⁴⁵Ca exchange, having higher rate than R Na/⁴⁰Ca exchange, brings to depression of pain sensation, the mechanism of which is not clear. The previous data that the 4 Hz mechanical vibration (MV) has pain-relieving effects by activation of cGMP-dependent Na/Ca exchange in forward (F) mode, which leads to muscle hydration and neuronal dehydration, as in case of R Na/⁴⁵Ca exchange activation, allow us to suggest that the comparative study of the effects of 4 Hz MV and R Na/⁴⁵Ca exchange on thermal pain thresholds, tissue hydrations in different experimental conductions will make it possible to evaluate the mechanisms of R Na/⁴⁵Ca exchange-induced inhibition of pain sensation. The obtained data show that the R Na/⁴⁵Ca exchange-induced depression of pain sensation is due to high [Ca²⁺]_i-inactivation of Na/K pump which brings to further increase of [Ca²⁺]_i, while 4 Hz MV-activated F Na/Ca exchange-induced pain-relieving effect is due to Na/K pump activation by low [Ca²⁺]_i. It is suggested that the R Na/⁴⁵Ca exchange inhibits pain sensation, which is due to high [Ca²⁺]_i-induced depression inhibition of muscle contractility, while the 4 Hz MV-induced pain-relieving effect is due to activation of Na/K pump by cGMP-dependent decrease of [Ca²⁺]_i leading to muscle relaxation and neuronal dehydration. Therefore, the 4 Hz MV has been suggested as a novel quantum-mechanical sensitive target for pain therapy.