Kumamoto Eiichi
Faculty of Medicine, Saga University, 5-1-1 Nabeshima, Saga 849-8501, Japan.
Biomolecules. 2024 Dec 18;14(12):1619. doi: 10.3390/biom14121619.
Nociceptive information is transmitted by action potentials (APs) through primary afferent neurons from the periphery to the central nervous system. Voltage-gated Na channels are involved in this AP production, while transient receptor potential (TRP) channels, which are non-selective cation channels, are involved in receiving and transmitting nociceptive stimuli in the peripheral and central terminals of the primary afferent neurons. Peripheral terminal TRP vanilloid-1 (TRPV1), ankylin-1 (TRPA1) and melastatin-8 (TRPM8) activation produces APs, while central terminal TRP activation enhances the spontaneous release of L-glutamate from the terminal to spinal cord and brain stem lamina II neurons that play a pivotal role in modulating nociceptive transmission. There is much evidence demonstrating that chemical compounds involved in Na channel (or nerve AP conduction) inhibition modify TRP channel functions. Among these compounds are local anesthetics, anti-epileptics, α-adrenoceptor agonists, antidepressants (all of which are used as analgesic adjuvants), general anesthetics, opioids, non-steroidal anti-inflammatory drugs and plant-derived compounds, many of which are involved in antinociception. This review mentions the modulation of Na channels and TRP channels including TRPV1, TRPA1 and TRPM8, both of which modulations are produced by pain-related compounds.
伤害性信息通过动作电位（APs）由初级传入神经元从外周传递至中枢神经系统。电压门控钠通道参与AP的产生，而作为非选择性阳离子通道的瞬时受体电位（TRP）通道则参与在初级传入神经元的外周和中枢终末接收和传递伤害性刺激。外周终末的TRP香草酸受体1（TRPV1）、锚蛋白1（TRPA1）和褪黑素8（TRPM8）激活可产生AP，而中枢终末的TRP激活可增强从终末至脊髓和脑干II层神经元的L-谷氨酸的自发释放，这些神经元在调节伤害性传递中起关键作用。有许多证据表明，参与抑制钠通道（或神经AP传导）的化合物可改变TRP通道功能。这些化合物包括局部麻醉药、抗癫痫药、α-肾上腺素能受体激动剂、抗抑郁药（所有这些都用作镇痛佐剂）、全身麻醉药、阿片类药物、非甾体抗炎药和植物源性化合物，其中许多都与镇痛作用有关。本综述提及了钠通道和TRP通道（包括TRPV1、TRPA1和TRPM8）的调节，这两种调节均由疼痛相关化合物产生。
