Combined effect of Neurotropin® and methylcobalamin on postherpetic neuralgia in mice infected with herpes simplex virus type-1

Tsugunobu Andoh , Takashi Kikukawa , Atsushi Kotani , Yoko Kurokawa , Wakana Asakura , Kengo Houmoto , Daisuke Fukutomi , Daisuke Uta , Hisashi Okai , Koji Koike
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Abstract

Background

Postherpetic pain (PHP) is difficult to control. Although Neurotropin® (NTP) and methylcobalamin (MCB) are often prescribed to treat the pain, the efficacy of combined treatment for PHP remains imcompletely understood.

Objective

In this study, we investigate the combined effects of NTP and MCB on PHP in mice.

Methods

NTP and MCB were administered from day 10–29 after herpes simplex virus type-1 (HSV-1) infection. The pain-related responses were evaluated using a paint brush. The expression of neuropathy-related factor (ATF3) and nerve repair factors (GAP-43 and SPRR1A) in the dorsal root ganglion (DRG) and neurons in the skin were evaluated by immunohistochemical staining. Nerve growth factor (NGF) and neurotrophin-3 (NT3) mRNA expression levels were evaluated using real-time PCR.

Results

Repeated treatment with NTP and MCB after the acute phase inhibited PHP. Combined treatment with these drugs inhibited PHP at an earlier stage than either treatment alone. In the DRG of HSV-1-infected mice, MCB, but not NTP, decreased the number of cells expressing ATF3 and increased the number of cells expressing GAP-43- and SPRR1A. In addition, MCB, but not NTP, also increased and recovered non-myelinated neurons decreased in the lesional skin. NTP increased the mRNA levels of NTF3 in keratinocytes, while MCB increased that of NGF in Schwann cells.

Conclusion

These results suggest that combined treatment with NTP and MCB is useful for the treatment of PHP. The combined effect may be attributed to the different analgesic mechanisms of these drugs.

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神经营养素®和钴胺甲酯对感染 1 型单纯疱疹病毒的小鼠带状疱疹后遗神经痛的联合作用
背景带状疱疹后遗疼痛(PHP)很难控制。尽管神经妥乐平®(NTP)和甲钴胺(MCB)经常被用于治疗疼痛,但联合治疗 PHP 的疗效仍不完全清楚。方法在小鼠感染单纯疱疹病毒 1 型(HSV-1)后的第 10-29 天给予 NTP 和 MCB。用油漆刷评估与疼痛相关的反应。通过免疫组化染色评估了背根神经节(DRG)和皮肤神经元中神经病变相关因子(ATF3)和神经修复因子(GAP-43 和 SPRR1A)的表达。用实时 PCR 评估了神经生长因子(NGF)和神经营养素-3(NT3)的 mRNA 表达水平。与单独使用这两种药物相比,联合使用这两种药物能更早地抑制 PHP。在 HSV-1 感染小鼠的 DRG 中,MCB(而非 NTP)减少了表达 ATF3 的细胞数量,增加了表达 GAP-43- 和 SPRR1A 的细胞数量。此外,MCB(而非 NTP)还增加了病变皮肤中的非髓鞘神经元数量,并减少了恢复的非髓鞘神经元数量。NTP 增加了角朊细胞中 NTF3 的 mRNA 水平,而 MCB 增加了许旺细胞中 NGF 的 mRNA 水平。这些结果表明,NTP 和 MCB 联合治疗对 PHP 有一定的疗效,其联合作用可能归因于这两种药物不同的镇痛机制。
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