Géranton Sandrine M, Tochiki Keri K
Department of Cell and Developmental Biology, University College London, London, United Kingdom.
Department of Cell and Developmental Biology, University College London, London, United Kingdom.
Prog Mol Biol Transl Sci. 2015;131:147-83. doi: 10.1016/bs.pmbts.2014.11.012. Epub 2015 Feb 15.
The induction of inflammatory or neuropathic pain states is known to involve molecular activity in the spinal superficial dorsal horn and dorsal root ganglia, including intracellular signaling events which lead to changes in gene expression. These changes ultimately cause alterations in macromolecular synthesis, synaptic transmission, and structural architecture which support central sensitization, a process required for the establishment of long-term pain states. Epigenetic mechanisms are essential for long-term synaptic plasticity and modulation of gene expression. This is because epigenetic modifications are known to regulate gene transcription by aiding the physical relaxation or condensation of chromatin. These processes are therefore potential regulators of the molecular changes underlying permanent pain states. A handful of studies have emerged in the field of pain epigenetics; however, the field is still very much in its infancy. This chapter draws upon other specialities which have extensively investigated epigenetic mechanisms, such as learning and memory and oncology. After defining epigenetics as well as the recent field of "neuroepigenetics" and the main molecular mechanisms involved, this chapter describes the role of these mechanisms in the synaptic plasticity seen in learning and memory, and address those epigenetic mechanisms that have been linked with the development of acute and prolonged pain states. Finally, the idea that long-lasting epigenetic modifications could contribute to the transition from acute to chronic pain states by supporting maladaptive molecular changes is discussed.
已知炎症性或神经性疼痛状态的诱导涉及脊髓浅表背角和背根神经节中的分子活动，包括导致基因表达变化的细胞内信号转导事件。这些变化最终会引起大分子合成、突触传递和支持中枢敏化的结构架构的改变，而中枢敏化是建立长期疼痛状态所必需的过程。表观遗传机制对于长期突触可塑性和基因表达的调节至关重要。这是因为已知表观遗传修饰通过帮助染色质的物理松弛或凝聚来调节基因转录。因此，这些过程是永久性疼痛状态潜在的分子变化调节因子。疼痛表观遗传学领域已经出现了一些研究；然而，该领域仍处于起步阶段。本章借鉴了其他广泛研究表观遗传机制的专业领域，如学习与记忆以及肿瘤学。在定义表观遗传学以及最近的“神经表观遗传学”领域和所涉及的主要分子机制之后，本章描述了这些机制在学习与记忆中所见突触可塑性中的作用，并探讨了与急性和持续性疼痛状态发展相关的表观遗传机制。最后，讨论了持久的表观遗传修饰可能通过支持适应不良的分子变化而促成从急性疼痛状态向慢性疼痛状态转变的观点。
