Hagenacker T, Ledwig D, Büsselberg D
Universitätsklinikum Essen, Institut für Physiologie, Hufelandstrasse 55, 45122 Essen, Germany.
Cell Calcium. 2008 Mar;43(3):215-27. doi: 10.1016/j.ceca.2007.05.019. Epub 2007 Jul 27.
Multimodal stimuli like heat, cold, bacterial or mechanical events are able to elicit pain, which is necessary to guarantee survival. However, the control of pain is of major clinical importance. The perception and transduction of pain is differentially modulated in the peripheral and central nervous system (CNS): while peripheral structures modulate these signals, the perception of pain occurs in the CNS. In recent years major advances have been made in the understanding of the processes which are involved in pain sensation. For the peripheral pain reception, the importance of specific pain receptors of the transition receptor pore (TRP)-family (e.g. the TRPV-1 receptor) has been analyzed. These receptors/channels are localized at the cell membrane of nociceptive neurones as well as in membranes of intracellular calcium stores like the endoplasmic reticulum. While the associated channel conducts different ions, a major proportion is calcium. Therefore, this review focuses on (1) the modulations of intracellular calcium ([Ca2+]i) initiated by the activation of pain receptors and (2) the consequences of [Ca2+]i changes for the processing of pain signals at the peripheral side. The possible interference of TRPV-1 induced [Ca2+]i modulations to the function of other membrane receptors and channels, like voltage gated calcium, sodium or potassium channels, or co-expressed CB1-receptors will be discussed. The latter interactions are of specific interest since the analgetic properties of endo- and exo-cannabinoids are mediated by CB1 receptors and their activation significantly modulates the calcium induced release of pain related transmitters. Furthermore, multiple cross links between different pain modulating intracellular pathways and their dependence on [Ca2+]i modulations will be illuminated. Overall, this review will summarize new insights resulting in the understanding of the prominent influence of [Ca2+]i for processes which are involved in pain sensation.
热、冷、细菌或机械刺激等多模态刺激能够引发疼痛，而疼痛对于保证生存是必要的。然而，疼痛控制具有重大的临床意义。疼痛的感知和传导在外周和中枢神经系统（CNS）中受到不同的调节：虽然外周结构调节这些信号，但疼痛的感知发生在中枢神经系统。近年来，在理解疼痛感觉所涉及的过程方面取得了重大进展。对于外周疼痛感受，已经分析了瞬时受体电位通道（TRP）家族的特定疼痛受体（例如TRPV-1受体）的重要性。这些受体/通道定位于伤害性神经元的细胞膜以及内质网等细胞内钙库的膜上。虽然相关通道传导不同的离子，但主要是钙。因此，本综述重点关注（1）由疼痛受体激活引发的细胞内钙（[Ca2+]i）的调节，以及（2）外周侧[Ca2+]i变化对疼痛信号处理的影响。将讨论TRPV-1诱导的[Ca2+]i调节对其他膜受体和通道功能的可能干扰，如电压门控钙通道、钠通道或钾通道，或共表达的CB1受体。后一种相互作用特别令人感兴趣，因为内源性和外源性大麻素的镇痛特性是由CB1受体介导的，它们的激活会显著调节钙诱导的疼痛相关递质的释放。此外，将阐明不同疼痛调节细胞内途径之间的多个交叉联系及其对[Ca2+]i调节的依赖性。总体而言，本综述将总结在理解[Ca2+]i对疼痛感觉相关过程的显著影响方面产生的新见解。
