The Na(V)1.7 Channel Subtype as an Antinociceptive Target for Spider Toxins in Adult Dorsal Root Ganglia Neurons.
The Na(V)1.7 Channel Subtype as an Antinociceptive Target for Spider Toxins in Adult Dorsal Root Ganglia Neurons.
复制标题
DOI：
10.3389/fphar.2018.01000
复制
发表时间：
2018
影响因子：
5.6
通讯作者：
Servent D
中科院分区：
文献类型：
--
作者：
Gonçalves TC;Benoit E;Partiseti M;Servent D
虽然疼痛是人类生存所必需的，但如果持续时间长，并且与其信号通路的改变有关，有时可能会成为病理性的。阿片类止痛药被正式用于治疗中度至重度，甚至轻度疼痛。然而，随之而来的强烈和不那么罕见的并发症，包括成瘾和过量，加上疼痛管理成本，仍然是一个重要的社会和经济问题。在这种情况下，动物毒液毒素代表主要靶向参与疼痛传递的离子通道（如ASIC以及TRP、CaV、KV和NaV通道）的抗伤害感受肽的原始来源。本综述的目的是突出的NaV1.7通道亚型作为一个抗伤害性的目标蜘蛛毒素在成人背根神经节神经元。它将详细说明（i）这些初级感觉神经元的特征，这些初级感觉神经元是第一个与疼痛刺激接触并传递伤害性信息的神经元，（ii）这些神经元中表达的不同NaV通道亚型的电生理特性，特别关注NaV1.7亚型，这是一种已被人类遗传证据验证的抗伤害性选择靶点，和（iii）蜘蛛毒毒素的特征，其形状为抑制性半胱氨酸结基序，其对NaV1.7亚型呈现高亲和力，与动物模型中证实的镇痛功效相关。
Although necessary for human survival, pain may sometimes become pathologic if long-lasting and associated with alterations in its signaling pathway. Opioid painkillers are officially used to treat moderate to severe, and even mild, pain. However, the consequent strong and not so rare complications that occur, including addiction and overdose, combined with pain management costs, remain an important societal and economic concern. In this context, animal venom toxins represent an original source of antinociceptive peptides that mainly target ion channels (such as ASICs as well as TRP, CaV, KV and NaV channels) involved in pain transmission. The present review aims to highlight the NaV1.7 channel subtype as an antinociceptive target for spider toxins in adult dorsal root ganglia neurons. It will detail (i) the characteristics of these primary sensory neurons, the first ones in contact with pain stimulus and conveying the nociceptive message, (ii) the electrophysiological properties of the different NaV channel subtypes expressed in these neurons, with a particular attention on the NaV1.7 subtype, an antinociceptive target of choice that has been validated by human genetic evidence, and (iii) the features of spider venom toxins, shaped of inhibitory cysteine knot motif, that present high affinity for the NaV1.7 subtype associated with evidenced analgesic efficacy in animal models.
登录
查看更多内容
影响因子：
7.4
作者：
Blesneac I;Themistocleous AC;Fratter C;Conrad LJ;Ramirez JD;Cox JJ;Tesfaye S;Shillo PR;Rice ASC;Tucker SJ;Bennett DLH
通讯作者：
Bennett DLH
影响因子：
4.6
作者：
Anderson, Lyndsey L.;Hawkins, Nicole A.;George, Alfred L., Jr.
通讯作者：
George, Alfred L., Jr.
影响因子：
5.4
作者：
Boullot F;Castrec J;Bidault A;Dantas N;Payton L;Perrigault M;Tran D;Amzil Z;Boudry P;Soudant P;Hégaret H;Fabioux C
通讯作者：
Fabioux C
影响因子：
3.6
作者：
Bosmans, F;Rash, L;Tytgat, J
通讯作者：
Tytgat, J
影响因子：
3
作者：
CAVIEDES, P;AULT, B;RAPOPORT, SI
通讯作者：
RAPOPORT, SI