Epigenetic modification in neuropathic pain.
Epigenetic modification in neuropathic pain.
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DOI：
10.2174/1381612820666141027113923
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发表时间：
2014-12
影响因子：
3.1
通讯作者：
H. Ueda;H. Uchida
中科院分区：
文献类型：
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作者：
H. Ueda;H. Uchida
神经性疼痛的特征在于复杂的阳性（例如，痛觉过敏和异常性疼痛）和阴性（例如，感觉减退和痛觉减退）症状，并且通常对常规药理学试剂（包括吗啡）无效。虽然阳性症状的分子机制被广泛研究，但对阴性症状的分子机制知之甚少。有令人信服的证据表明，外周和中枢神经系统内基因表达的改变是神经性疼痛的关键机制;然而，其转录机制却知之甚少。表观遗传修饰，如DNA甲基化和组蛋白修饰（例如，乙酰化、甲基化和磷酸化），已知通过染色质重塑引起稳定的基因表达。这些机制不仅在决定发育细胞的命运中起作用，而且在神经系统的生理和病理过程中也起作用。此外，使用表观遗传修饰化合物的表观遗传疗法在治疗包括癌症和神经系统疾病在内的多种疾病中逐渐发展。重要的是，有新的证据表明，各种基因通过外周和中枢神经系统内的DNA甲基化和组蛋白修饰进行表观遗传调控，从而有助于神经性疼痛的疼痛敏感性和药理学功效的改变。本文就神经病理性疼痛的表观遗传基因调控作一综述，特别关注神经病理性疼痛的阴性症状。此外，我们将讨论表观遗传机制是否可以作为一个潜在的目标，以治疗神经病理性疼痛。
Neuropathic pain is characterized by complicated combination of positive (e.g., hyperalgesia and allodynia) and negative (e.g., hypoesthesia and hypoalgesia) symptoms, and is often refractory to conventional pharmacological agents, including morphine. Although the molecular mechanisms for positive symptoms are extensively studied, those for negative symptoms are poorly understood. There is convincing evidence that altered gene expression within peripheral and central nervous systems is a key mechanism for neuropathic pain; however, its transcriptional mechanisms are poorly understood. Epigenetic modifications, such as DNA methylation and histone modifications (e.g., acetylation, methylation, and phosphorylation), are known to cause stable gene expression via chromatin remodeling. These mechanisms have a role not only in the determination of developmental cell fates, but also in the physiological and pathological processes in nervous system. Moreover, epigenetic therapies using epigenetic modifying compounds are progressively advanced in the treatments of diverse diseases, including cancer and neurological diseases. Importantly, there is emerging evidence that a variety of genes undergo epigenetic regulation via DNA methylation and histone modifications within peripheral and central nervous systems, thereby contributing to the alterations in both pain sensitivity and pharmacological efficacy in neuropathic pain. In this review, we will highlight the epigenetic gene regulation underlying neuropathic pain, especially focusing on the negative symptoms. Moreover, we will discuss whether epigenetic mechanisms can serve as a potential target to treat neuropathic pain.