Beyond lidocaine: selective voltage-gated sodium channel blockade for vaginal pain.
Beyond lidocaine: selective voltage-gated sodium channel blockade for vaginal pain.
复制标题
超越利多卡因：选择性电压门控钠通道阻断治疗阴道疼痛。
DOI：
10.1097/j.pain.0000000000002037
复制
发表时间：
2021
期刊：
影响因子：
7.4
通讯作者：
Ross,SarahE
中科院分区：
文献类型：
--
作者：
Holland,RubyA;Ross,SarahE
女性生殖道疼痛包括各种常见的和使人衰弱的病症，如外阴痛、继发于子宫内膜异位症的阴道痛觉过敏、阴部神经痛等。这些疾病缺乏有效的药物治疗，因为对女性生殖器官的感觉传递机制缺乏了解。研究膀胱和结肠伤害性感受的研究表明，不同的电压门控钠（NaV）通道在疼痛传递中起着关键和复杂的作用，这表明选择性钠通道阻滞可能是盆腔疼痛的更有效的治疗策略。8，9然而，没有研究专门研究NaV通道在生殖道疼痛信号传导中的作用。在本期的《疼痛》杂志上，Castro等人3解决了这一知识空白。配备了一种新的离体阴道制备物，作者研究了支配小鼠阴道的骨盆神经传入的机械感觉特性和感受野（图1和2）。图1A和B）。使用这种方法，这些传入被发现都是多模态的，与点状感受野分布沿着整个长度的阴道。有趣的是，这些mechanosensory反应，通过泛NaV通道激活剂藜芦定，但只有部分衰减的部分选择性NaV通道阻滞剂河豚毒素（TTX），这表明TTX耐NaV通道有助于显着传入传输从阴道。作者通过对从阴道逆行追踪的背根神经节（DRG）神经元进行单细胞聚合酶链反应（PCR）来补充这些结果，并发现NaV通道的丰富表达，每个亚型具有独特的表达模式（图1C）。最后，作者通过进行阴道球囊扩张和测量活体小鼠的内脏反应来测量阴道疼痛敏感性。他们发现，TTX减弱和藜芦碱增强体内疼痛反应，并类似地改变体外脊髓中的神经元活性（图1D）。
Female reproductive tract pain encompasses a variety of common and debilitating conditions such as vulvodynia, vaginal hyperalgesia secondary to endometriosis, pudendal neuralgia, and many others. These conditions lack effective pharmacotherapies due to a poor understanding of the mechanisms underlying sensory transmission from female reproductive organs. Studies investigating bladder and colon nociception have shown that different voltage-gated sodium (NaV) channels play a critical and complex role in pain transmission, suggesting selective sodium channel blockade may be a more potent therapeutic strategy for pelvic pain. 8, 9 However, no study has specifically investigated the role of NaV channels in pain signaling from the reproductive tract.In the present issue of PAIN, Castro et al. 3 address this gap in knowledge. Equipped with a novel ex vivo vaginal preparation, the authors investigated the mechanosensory properties and receptive fields of pelvic nerve afferents innervating the mouse vagina (Figs. 1A and B). Using this approach, these afferents were found to all be polymodal, with punctate receptive fields distributed along the entire length of the vagina. Interestingly, these mechanosensory responses were globally augmented through the pan-NaV channel activator veratridine but only partly attenuated by the partially selective NaV channel blocker tetrodotoxin (TTX), suggesting that TTX-resistant NaV channels contribute significantly to afferent transmission from the vagina. The authors complement these results by performing single-cell polymerase chain reaction (PCR) on dorsal root ganglion (DRG) neurons retrogradely traced from the vagina and found abundant expression of NaV channels, with distinctive expression patterns across each subtype (Fig. 1C). Finally, the authors measured vaginal pain sensitivity by performing vaginal balloon distention and measuring visceromotor responses in live mice. They found that TTX attenuated and veratridine enhanced pain responses in vivo and similarly altered neuronal activity in the spinal cord in vitro (Fig. 1D).