Ningbo Pace Translational Medical Research Center, Beilun, Ningbo, China.
Am J Physiol Gastrointest Liver Physiol. 2013 Aug 15;305(4):G333-9. doi: 10.1152/ajpgi.00224.2012. Epub 2013 Jun 13.
Desvenlafaxine succinate (DVS) is a novel serotonin and norepinephrine reuptake inhibitor. The aim of this study was to investigate the effects of DVS on visceral hypersensitivity and solid gastric emptying in a rodent model of gastric hyperalgesia. Twenty-eight gastric hyperalgesia rats and 20 control rats were used. Visceral sensitivity during gastric distention (GD) was assessed by recording of electromyogram (EMG) at pressures of 20, 40, 60, and 80 mmHg. DVS with doses of 1, 10, and 30 mg/kg were administrated by gavage, 5-HT1A antagonist (WAY-100635, 0.3 mg/kg) was given subcutaneously, and 5-HT2A antagonist (ketanserin, 1 mg/kg) was given intraperitoneally. The level of norepinephrine in plasma was measured by enzyme-linked immunosorbent assay. We found that 1) visceral hypersensitivity induced by acetic acid was validated. 2) DVS dose-dependently reduced visceral hypersensitivity in the gastric hypersensitivity rats. The EMG (% of baseline value without GD) during GD at 60 and 80 mmHg with DVS at a dose of 30 mg/kg were 119.4 ± 2.3% (vs. saline 150.9 ± 2.7%, P < 0.001) and 128.2 ± 3.2% (vs. saline 171.1 ± 2.4%, P < 0.001). Similar findings were observed at a dose of 10 mg/kg. DVS at a dose of 1 mg/kg reduced visceral hypersensitivity only during GD at 60 mmHg. 3) Neither WAY-100635 nor ketanserin blocked the effect of DVS on visceral sensitivity. 4) DVS at 30 mg/kg significantly increased plasma NE level (P = 0.012 vs. saline). 5) DVS at 30 mg/kg significantly delayed solid gastric emptying (P < 0.05 vs. saline). We conclude that DVS reduces visceral sensitivity in a rodent model of visceral hypersensitivity and delays solid gastric emptying. Caution should be made when DVS is used for treating patients.
琥珀酸去甲文拉法辛（DVS）是一种新型的 5-羟色胺和去甲肾上腺素再摄取抑制剂。本研究旨在探讨 DVS 对胃高敏感大鼠内脏敏感性和固体胃排空的影响。使用 28 只胃高敏感大鼠和 20 只对照大鼠。通过记录胃扩张（GD）时的肌电图（EMG）来评估内脏敏感性，GD 时的压力分别为 20、40、60 和 80mmHg。DVS 以 1、10 和 30mg/kg 的剂量灌胃，5-HT1A 拮抗剂（WAY-100635，0.3mg/kg）皮下给药，5-HT2A 拮抗剂（酮色林，1mg/kg）腹腔内给药。通过酶联免疫吸附试验测量血浆中去甲肾上腺素的水平。我们发现：1）验证了乙酸诱导的内脏敏感性；2）DVS 剂量依赖性地降低了胃高敏感大鼠的内脏敏感性。DVS 30mg/kg 剂量组在 GD 时 60 和 80mmHg 时的 EMG（无 GD 时的基线值的%）分别为 119.4±2.3%（与盐水组 150.9±2.7%相比，P<0.001）和 128.2±3.2%（与盐水组 171.1±2.4%相比，P<0.001）。在 10mg/kg 剂量时也观察到类似的发现。DVS 1mg/kg 剂量仅在 GD 时 60mmHg 时降低内脏敏感性。3）WAY-100635 和酮色林均不能阻断 DVS 对内脏敏感性的影响。4）DVS 30mg/kg 剂量显著增加血浆 NE 水平（与盐水组相比，P=0.012）。5）DVS 30mg/kg 剂量显著延迟固体胃排空（与盐水组相比，P<0.05）。我们的结论是，DVS 降低了内脏高敏感大鼠模型的内脏敏感性，并延迟了固体胃排空。在治疗患者时应谨慎使用 DVS。
