ABSTRACT

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.

摘要

^{导致神经元肿胀和肌肉收缩的反向 (R) 模式中 Na/ 40} Ca 交换的激活已被建议作为产生疼痛信号的机制。^{然而，R Na/ 45} Ca 交换的激活，比R Na/ ⁴⁰ Ca 交换的速率更高，导致痛觉抑制，其机制尚不清楚。先前的数据表明 4 Hz 机械振动 (MV) 通过激活正向 (F) 模式中依赖于 cGMP 的 Na/Ca 交换具有镇痛作用，这导致肌肉水化和神经元脱水，如 R Na/ ⁴⁵ Ca 交换激活，允许我们建议比较研究 4 Hz MV 和 R Na/ ^{45Ca 交换对热痛阈值的影响，不同实验传导中的组织水合作用，将使评估 R Na/ 45} Ca 交换诱导的痛觉抑制机制成为可能。获得的数据表明，R Na/ ⁴⁵ Ca 交换引起的痛觉抑制是由于高 [Ca ²⁺ ] _{i– Na/K 泵失活导致 [Ca} ²⁺ ] _i进一步增加，而 4 Hz MV 激活的 F Na/Ca 交换诱导的止痛作用是由于低 [Ca ²⁺ ] _i引起的 Na/K 泵激活。表明 R Na/ ⁴⁵ Ca 交换抑制痛觉，这是由于高 [Ca ²⁺] _i–诱导抑制肌肉收缩力，而 4 Hz MV 诱导的镇痛作用是由于 [Ca 2+ ] i 的 cGMP 依赖性减少激活 Na/K 泵，导致肌肉松弛和^神经元_脱水。因此，4 Hz MV 已被建议作为疼痛治疗的新型量子力学敏感靶点。