Epigenetic Modifications Associated to Neuroinflammation and Neuropathic Pain After Neural Trauma.
Epigenetic Modifications Associated to Neuroinflammation and Neuropathic Pain After Neural Trauma.
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DOI：
10.3389/fncel.2018.00158
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发表时间：
2018
影响因子：
5.3
通讯作者：
Navarro X
中科院分区：
文献类型：
--
作者：
Penas C;Navarro X
越来越多的证据表明，表观遗传学的改变背后的诱导和维持的神经性疼痛。神经性疼痛通常是由神经系统内的病变或病理变化引起的慢性病症。神经性疼痛常出现在神经和脊髓损伤或疾病后，导致患者虚弱和生活质量下降。在细胞水平上，神经性疼痛是中枢和外周神经系统感觉神经元的敏感性和兴奋性增加所形成的神经元可塑性的结果。被认为导致过度兴奋并因此导致神经性疼痛的个体发生的机制之一是由初级感觉神经元表达的受体和离子通道的表达、运输和功能改变。此外，神经元和神经胶质细胞，如小胶质细胞和星形胶质细胞，与血液传播的巨噬细胞一起，通过释放强大的神经调节剂，如促炎细胞因子和趋化因子，增强神经元的兴奋性，在神经病理性疼痛的诱导和维持中发挥关键作用。神经元受体、离子通道和促炎细胞因子和趋化因子的基因表达改变与损伤组织的表观遗传适应相关。在这篇综述中，我们讨论了这些表观遗传变化的参与，包括组蛋白修饰，DNA甲基化，非编码RNA和染色质修饰剂的改变，已被证明是引发神经病变后的伤害感受的修改。特别地，描述了EZH2、JMJD3、MeCP2、几种组蛋白脱乙酰基酶（HDAC）和组蛋白乙酰基转移酶（HAT）、G9a、DNMT、REST和多种非编码RNA在这些过程中的功能。尽管努力开发新的治疗方法，但目前的治疗方法仅在一部分患者中产生了有限的疼痛缓解。因此，本综述旨在为慢性神经病理性疼痛的治疗寻找新的靶点。
Accumulating evidence suggests that epigenetic alterations lie behind the induction and maintenance of neuropathic pain. Neuropathic pain is usually a chronic condition caused by a lesion, or pathological change, within the nervous system. Neuropathic pain appears frequently after nerve and spinal cord injuries or diseases, producing a debilitation of the patient and a decrease of the quality of life. At the cellular level, neuropathic pain is the result of neuronal plasticity shaped by an increase in the sensitivity and excitability of sensory neurons of the central and peripheral nervous system. One of the mechanisms thought to contribute to hyperexcitability and therefore to the ontogeny of neuropathic pain is the altered expression, trafficking, and functioning of receptors and ion channels expressed by primary sensory neurons. Besides, neuronal and glial cells, such as microglia and astrocytes, together with blood borne macrophages, play a critical role in the induction and maintenance of neuropathic pain by releasing powerful neuromodulators such as pro-inflammatory cytokines and chemokines, which enhance neuronal excitability. Altered gene expression of neuronal receptors, ion channels, and pro-inflammatory cytokines and chemokines, have been associated to epigenetic adaptations of the injured tissue. Within this review, we discuss the involvement of these epigenetic changes, including histone modifications, DNA methylation, non-coding RNAs, and alteration of chromatin modifiers, that have been shown to trigger modification of nociception after neural lesions. In particular, the function on these processes of EZH2, JMJD3, MeCP2, several histone deacetylases (HDACs) and histone acetyl transferases (HATs), G9a, DNMT, REST and diverse non-coding RNAs, are described. Despite the effort on developing new therapies, current treatments have only produced limited relief of this pain in a portion of patients. Thus, the present review aims to contribute to find novel targets for chronic neuropathic pain treatment.
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影响因子：
32.4
作者：
Cronk JC;Derecki NC;Ji E;Xu Y;Lampano AE;Smirnov I;Baker W;Norris GT;Marin I;Coddington N;Wolf Y;Turner SD;Aderem A;Klibanov AL;Harris TH;Jung S;Litvak V;Kipnis J
通讯作者：
Kipnis J
影响因子：
64.5
作者：
Ballas, N;Grunseich, C;Mandel, G
通讯作者：
Mandel, G
影响因子：
13.9
作者：
Costigan M;Scholz J;Woolf CJ
通讯作者：
Woolf CJ
影响因子：
3.3
作者：
Bali KK;Hackenberg M;Lubin A;Kuner R;Devor M
通讯作者：
Devor M
影响因子：
3.1
作者：
Capasso, Kathryn E.;Manners, Melissa T.;Ajit, Seena K.
通讯作者：
Ajit, Seena K.