Recently the voltage-gated sodium (Nav) channels began to be studied as possible targets for analgesic drugs. In addition, specific Nav 1.8 blockers are currently being used to treat some types of chronic pain pathologies such as neuropathies and fibromyalgia. Nav 1.8+ fibers convey nociceptive information to brain structures belonging to the limbic system, which is involved in the pathophysiology of major depressive disorders. From this, using a model of chronic social defeat stress (SDS) and intrathecal injections of Nav 1.8 antisense, this study investigated the possible involvement of Nav 1.8+ nociceptive fibers in SDS- induced hyperalgesia in C57/BL mice. Our results showed that SDS induced a depressive-like behavior of social avoidance and increased the sensitivity to mechanical (electronic von Frey test) and chemical (capsaicin test) nociceptive stimuli. We also showed that intrathecal injection of Nav 1.8 antisense reversed the SDS-induced hyperalgesia as demonstrated by both, mechanical and chemical nociceptive tests. We confirmed the antisense efficacy and specificity in a separate no-defeated cohort through real-time PCR, which showed a significant reduction of Nav 1.8 mRNA and no reduction of Nav 1.7 and Nav 1.9 in the L4, L5 and L6 dorsal root ganglia (DRG). The present study advances the understanding of SDS-induced hyperalgesia, which seems to be dependent on Nav 1.8+ nociceptive fibers.

中文翻译：

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社交失败压力诱发的痛觉过敏是由nav 1.8+伤害性纤维介导的。

最近，电压门控钠（Nav）通道开始被​​研究为止痛药的可能靶标。另外，目前正在使用特定的Nav 1.8阻滞剂来治疗某些类型的慢性疼痛病状，例如神经病和纤维肌痛。Nav 1.8+纤维将伤害性信息传递到属于边缘系统的大脑结构，该结构与主要抑郁症的病理生理有关。由此，本研究使用慢性社交失败应激（SDS）模型和鞘内注射Nav 1.8反义物，研究了Nav 1.8+伤害性纤维可能参与了C57 / BL小鼠SDS诱导的痛觉过敏。我们的结果表明，SDS会引起社交回避的抑郁样行为，并增加了对机械（电子von Frey测试）和化学（辣椒素测试）伤害性刺激的敏感性。我们还显示鞘内注射Nav 1.8反义可逆转SDS诱导的痛觉过敏，如机械和化学伤害试验所证实。我们通过实时PCR在一个独立的不败人群中证实了反义功效和特异性，该研究显示L4，L5和L6背根神经节（DRG）中Nav 1.8 mRNA显着降低，而Nav 1.7和Nav 1.9均未降低）。本研究提高了对SDS诱导的痛觉过敏的理解，后者似乎依赖于Nav 1.8+伤害性纤维。机械和化学伤害试验均显示8反义逆转了SDS诱导的痛觉过敏。我们通过实时PCR在一个独立的不败人群中证实了反义功效和特异性，该研究显示L4，L5和L6背根神经节（DRG）中Nav 1.8 mRNA显着降低，而Nav 1.7和Nav 1.9均未降低）。本研究提高了对SDS诱导的痛觉过敏的理解，后者似乎依赖于Nav 1.8+伤害性纤维。机械和化学伤害试验均显示8反义逆转了SDS诱导的痛觉过敏。我们通过实时PCR在一个独立的不败人群中证实了反义功效和特异性，该研究显示L4，L5和L6背根神经节（DRG）中Nav 1.8 mRNA的显着减少以及Nav 1.7和Nav 1.9的减少）。本研究提高了对SDS诱导的痛觉过敏的理解，后者似乎依赖于Nav 1.8+伤害性纤维。