Sodium valproate (VPA) has analgesic effects in clinical and experimental studies, but the mechanisms are still unclear. The present study examined the effects of VPA on stress-induced somatic hyperalgesia and visceral hypersensitivity and the role of 5-HT2C receptors in the spinal cord. Repeated 3 day forced swim (FS) significantly reduced the thermal withdrawal latency and mechanical withdrawal threshold, and increased the magnitude of the visceromotor response to colorectal distention compared to the baseline values in rats. The somatic hyperalgesia and visceral hypersensitivity were accompanied by significant down-regulation of 5-HT2C receptor expression in the L4-L5 and L6-S1 dorsal spinal cord. Intraperitoneal administration of VPA (300 mg/kg) before each FS and 1 day post FS prevented the development of somatic hyperalgesia and visceral hypersensitivity induced by FS stress, as well as down-regulation of 5-HT2C receptors in the spinal cord. The reversal of somatic hyperalgesia and visceral hypersensitivity by VPA in FS rats was blocked by intrathecal administration of the selective 5-HT2C receptor antagonist RS-102221 (30 μg/10 μL) 30 min after each VPA injection. The results suggest that VPA attenuates FS-induced somatic hyperalgesia and visceral hypersensitivity by restoring down-regulated function of 5-HT2C receptors in the spinal cord.

中文翻译：

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丙戊酸盐通过上调雌性大鼠脊柱5-HT2C受体的表达来逆转应激诱导的躯体痛觉过敏和内脏超敏反应。

丙戊酸钠（VPA）在临床和实验研究中具有镇痛作用，但其机制尚不清楚。本研究检查了VPA对应激诱导的体痛觉过敏和内脏超敏反应的影响以及脊髓中5-HT2C受体的作用。与大鼠的基线值相比，重复3天的强迫游泳（FS）显着降低了热退缩潜伏期和机械退缩阈值，并增加了对结直肠扩张的内脏运动反应的幅度。躯体痛觉过敏和内脏超敏反应伴随着L4-L5和L6-S1背脊髓中5-HT2C受体表达的显着下调。在每个FS前和FS后1天腹膜内给予VPA（300 mg / kg）可以防止由FS应力引起的体细胞痛觉过敏和内脏超敏反应的发展，以及脊髓中5-HT2C受体的下调。在每次VPA注射后30分钟，通过鞘内施用选择性5-HT2C受体拮抗剂RS-102221（30μg/ 10μL）来阻止FS大鼠的VPA逆转体痛觉过敏和内脏超敏反应。结果表明，VPA通过恢复脊髓中5-HT2C受体的下调功能来减轻FS引起的体细胞痛觉过敏和内脏超敏反应。在每次VPA注射后30分钟，通过鞘内施用选择性5-HT2C受体拮抗剂RS-102221（30μg/ 10μL）来阻止FS大鼠的VPA逆转体痛觉过敏和内脏超敏反应。结果表明，VPA通过恢复脊髓中5-HT2C受体的下调功能来减轻FS引起的体细胞痛觉过敏和内脏超敏反应。在每次VPA注射后30分钟，通过鞘内施用选择性5-HT2C受体拮抗剂RS-102221（30μg/ 10μL）来阻止FS大鼠的VPA逆转体痛觉过敏和内脏超敏反应。结果表明，VPA通过恢复脊髓中5-HT2C受体的下调功能来减轻FS引起的体细胞痛觉过敏和内脏超敏反应。