Genetic insights toward improved management of chronic pain after mastectomy.
Genetic insights toward improved management of chronic pain after mastectomy.
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改善乳房切除术后慢性疼痛管理的遗传学见解。
DOI：
10.1097/01.j.pain.0000460337.39223.d9
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发表时间：
2015
期刊：
影响因子：
7.4
通讯作者：
Tsantoulas C
中科院分区：
文献类型：
--
作者：
Tsantoulas C
慢性乳房疼痛是高达50%的接受乳房切除术（乳房切除术）的癌症患者的手术并发症。15这种类型的疼痛通常是由于直接神经（通常是肋间臂神经）或软组织损伤引起的，通常伴有乳房幻觉和其他感觉异常。[26]对这种疾病的病理生理机制的认识是粗略的，现有的治疗方法在很大程度上是不够的。持续性疼痛的负担对这些患者来说特别虚弱，他们还遭受癌症治疗的心理社会和医疗压力。重要的是，疾病的预后是非常有问题的，因为遗传和环境因素，易患乳房疼痛仍然是未知的。疼痛敏感性和发展慢性疼痛的倾向是复杂的多基因性状，与30%至60%的持续性疼痛表型的变化归因于遗传因素。[33]现代神经科学使用了大量的DNA筛选方法来剖析在适应不良的疼痛处理中起主要作用的基因。许多研究都集中在离子通道上，因为这些蛋白质从根本上决定了痛觉神经元的放电特性和兴奋性。累积的研究现已确定，某些钾（K+）通道亚基在健康和疾病中与疼痛信号传导密切相关。29，31在这一期的PAIN®中，Langford等人17使用候选基因方法将乳房切除术后的持续性疼痛与5个K+通道基因中的各种SNP联系起来，即KCNA 1（Kv 1. 1）、KCND2（Kv4. 2）、GIRK 1、GIRK 2和TASK 3。虽然遗传筛选不能解释SNP对蛋白质活性本身的影响，但其他K+通道的经验表明，SNP增强这些通道的传导可能导致兴奋性降低和抗伤害感受。[29]有趣的是，一些已鉴定的SNP位于非编码区，如RNA结合结构域或甲基化底物。除非与未确定的功能SNP连锁不平衡，否则这一观察结果支持表观遗传修饰在疼痛中的新作用。6
Chronic breast pain is a surgical complication in up to 50% of patients with cancer undergoing breast removal (mastectomy). 15 This type of pain usually arises as a consequence of direct nerve (typically the intercostobrachial nerve) or soft tissue injury and is often accompanied by breast phantoms and other paraesthesias. 26 Mechanistic insight on the pathophysiology of the condition is sketchy and existing treatments are largely inadequate. The burden of persistent pain is particularly debilitating for these patients, who also suffer the psychosocial and medical stress of cancer treatment. Importantly, disease prognosis is extremely problematic because the genetic and environmental factors that predispose to breast pain remain unknown.Both pain sensitivity and propensity for developing chronic pain are complex polygenic traits, with 30% to 60% of the variation in persistent pain phenotypes attributed to heritable factors. 33 Modern neuroscience uses a plethora of DNA screening methodologies to dissect genes with predominant roles in maladaptive pain processing. Many studies focus on ion channels because these proteins fundamentally determine firing properties and excitability of pain-sensing neurons. Accumulating research has now established that certain potassium (K+) channel subunits are vitally involved in pain signalling in both health and disease. 29, 31 In this issue of PAIN®, Langford et al. 17 use a candidate gene approach to link persistent pain after mastectomy with various SNPs in 5 K+ channel genes, namely KCNA1 (Kv1. 1), KCND2 (Kv4. 2), GIRK1, GIRK2, and TASK3. Although genetic screening cannot interpret the SNP effect on protein activity per se, experience with other K+ channels suggests that pharmacologically enhancing conduction of these channels may lead to decreased excitability and antinociception. 29 Interestingly, some of the identified SNPs are located in noncoding regions, such as RNA-binding domains or methylation substrates. Unless in linkage disequilibrium with undetermined functional SNPs, this observation supports the emerging role of epigenetic modifications in pain. 6
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