Silencing Transient Receptor Potential Vanilloid Receptor Subtype I-containing Sensory Neurons to Treat Bone Cancer Pain.
Silencing Transient Receptor Potential Vanilloid Receptor Subtype I-containing Sensory Neurons to Treat Bone Cancer Pain.
复制标题
沉默瞬时受体电位香草酸受体 I 亚型感觉神经元来治疗骨癌疼痛。
DOI：
10.1097/aln.0000000000001153
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发表时间：
2016
期刊：
影响因子：
8.8
通讯作者：
Peters,ChristopherM
中科院分区：
文献类型：
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作者：
Peters,ChristopherM
将近一半的癌症患者在他们的疾病过程中会经历疼痛。原发性肿瘤存在或转移到骨骼时发生的疼痛是75-90%晚期癌症患者中最常见和最严重的癌症疼痛类型。癌症引起的骨痛包括持续的疼痛，在性质上是迟钝的，持续的和进行性的。骨癌疼痛也可以由运动引发，并产生强烈的疼痛发作，突破了标准的阿片类药物治疗方案，严重限制了日常活动和整体生活质量。目前用于治疗骨癌疼痛的治疗方法包括放疗、阿片类药物、双膦酸盐和非甾体类抗炎药并不完全有效，并且可能存在不良副作用，限制了它们的使用。因此，迫切需要新的镇痛方法。在本期《麻醉学》杂志上，Fuseya等人发表了一项啮齿动物研究的数据，提出了一种治疗和缓解转移性骨痛的新方法，包括全身给药钠通道阻滞剂QX-3141。QX-314是一种带正电的季系利多卡因衍生物，通过神经膜的渗透性有限。在相对高浓度（10-70mM）时，QX-314通过神经膜扩散，在小鼠中产生感觉和运动阻断2。几年前，Woolf及其同事开发了一种选择性沉默伤害感觉神经元的方法，该方法涉及到在神经周围给药低浓度（5.8 mM）的QX-314和瞬时受体电位香草样蛋白1型（TRPV1）激动剂3，导致长期的感觉选择性神经阻滞，而不损害运动功能或触觉。TRPV1是一种表达于痛觉感觉神经元上的大孔阳离子通道，可被多种产生疼痛的刺激激活，包括有害热量、细胞外质子（pH< 6.0）、膜源性脂质和辣椒素（辣椒中的有害成分）。辣椒素与QX-314一起在神经周围给药，打开TRPV1通道孔，允许QX-314进入，最大限度地长期阻断钠通道。Fuseya及其同事假设，在TRPV1被激活的病理状态下，
Nearly half of all cancer patients will experience pain during the course of their disease. Pain that occurs when primary tumors are present in or metastasize to bone is the most common and severe type of cancer pain reported in 75–90% of late stage cancer patients. Cancer induced bone pain consists of ongoing pain that is dull in character, persistent and progressive. Bone cancer pain can also be triggered by movement and produce episodes of intense pain that breakthrough a standard opioid-based regimen significantly limiting daily activity and overall quality of life. Current therapies used to manage bone cancer pain including radiotherapy, opioids, bisphosphonates, and nonsteroidal anti-inflammatory drugs are not completely effective and may be associated with adverse side effects that limit their use. Thus, new analgesic approaches are desperately needed. In this issue of Anesthesiology, Fuseya et al. present data from a rodent study to suggest a novel approach for treatment and relief from metastatic bone pain involving systemic administration of the sodium channel blocking agent QX-3141.QX-314 is a positively charged quaternary lidocaine derivative that has limited permeability through neural membranes. At relatively high concentrations (10–70mM) QX-314 diffuses through neural membranes to produce sensory and motor blockade in mice2. Several years ago, Woolf and colleagues developed an approach to selectively silence nociceptive sensory neurons that involves perineural administration of lower concentrations (5.8 mM) of QX-314 with transient receptor potential vanilloid type 1 (TRPV1) agonists3 leading to long term sensory selective nerve block without impairment of motor function or touch sensation. TRPV1 is a large pore cation channel expressed on nociceptive sensory neurons that is activated by multiple pain producing stimuli including noxious heat, extracellular protons (pH< 6.0), membrane derived lipids and capsaicin, the noxious ingredient in hot chili peppers. Perineural administration of capsaicin with QX-314 opens the TRPV1 channel pore allowing entry of QX-314 for maximal long term sodium channel blockade. Fuseya and colleagues hypothesize that in pathological conditions in which TRPV1 is activated,