Division of Gastroenterology and Hepatology, Stanford University Medical Center, Stanford, CA 94305-5187, USA.
Neurogastroenterol Motil. 2011 Apr;23(4):356-61, e160-1. doi: 10.1111/j.1365-2982.2010.01649.x. Epub 2011 Jan 4.
The amino acid γ-aminobutyric acid (GABA) is an important modulator of pain but its role in visceral pain syndromes is just beginning to be studied. Our aims were to investigate the effect and mechanism of action of the GABA(B) receptor agonist, baclofen, on gastric hypersensitivity in a validated rat model of functional dyspepsia (FD).
10-day-old male rats received 0.2 mL of 0.1% iodoacetamide in 2% sucrose daily by oral gavages for 6 days. Control group received 2% sucrose. At 8-10 weeks rats treated with baclofen (0.3, 1, and 3 mg kg(-1) bw) or saline were tested for behavioral and electromyographic (EMG) visceromotor responses; gastric spinal afferent nerve activity to graded gastric distention and Fos protein expression in dorsal horn of spinal cord segments T8-T10 to noxious gastric distention.
Baclofen administration was associated with a significant attenuation of the behavioral and EMG responses (at 1 and 3 mg kg(-1)) and expression of Fos in T8 and T9 segments in neonatal iodoacetamide sensitized rats. However, baclofen administration did not significantly affect splanchnic nerve activity to gastric distention. Baclofen (3 mg kg(-1)) also significantly reduced the expression of spinal Fos in response to gastric distention in control rats to a lesser extent than sensitized rats.
CONCLUSIONS & INFERENCES: Baclofen is effective in attenuating pain associated responses in an experimental model of FD and appears to act by central mechanisms. These results provide a basis for clinical trials of this drug in FD patients.
氨基酸 γ-氨基丁酸（GABA）是疼痛的重要调节剂，但它在内脏疼痛综合征中的作用才刚刚开始研究。我们的目的是研究 GABA（B）受体激动剂巴氯芬对功能性消化不良（FD）的大鼠模型中胃高敏性的作用和作用机制。
10 日龄雄性大鼠通过口服灌胃每天接受 0.2ml0.1%碘乙酰胺的 2%蔗糖溶液，共 6 天。对照组给予 2%蔗糖。在 8-10 周龄时，用巴氯芬（0.3、1 和 3mg/kg bw）或生理盐水处理大鼠，测试行为和肌电图（EMG）内脏运动反应；胃传入神经活动对分级胃扩张的反应和脊髓 T8-T10 背角的 Fos 蛋白表达对有害性胃扩张。
巴氯芬给药与行为和 EMG 反应的显著减弱（1 和 3mg/kg bw）以及新生碘乙酰胺敏感大鼠 T8 和 T9 段脊髓背角 Fos 表达相关。然而，巴氯芬给药对胃扩张引起的内脏神经活动没有显著影响。巴氯芬（3mg/kg bw）也显著降低了对照大鼠胃扩张时脊髓 Fos 的表达，但程度低于敏感大鼠。
巴氯芬可有效减轻 FD 实验模型中与疼痛相关的反应，其作用机制似乎是通过中枢机制。这些结果为该药物在 FD 患者中的临床试验提供了依据。
