The analgesic effects of the GABAB receptor agonist, baclofen, in a rodent model of functional dyspepsia.
The analgesic effects of the GABAB receptor agonist, baclofen, in a rodent model of functional dyspepsia.
复制标题
DOI：
10.1111/j.1365-2982.2010.01649.x
复制
发表时间：
2011-04-01
期刊：
影响因子：
--
通讯作者：
Pasricha, P J
中科院分区：
文献类型：
--
作者：
Liu, L S;Shenoy, M;Pasricha, P J
背景：氨基酸γ-氨基丁酸(GABA)是一种重要的疼痛调节剂，但其在内脏痛综合征中的作用研究刚刚开始。本研究旨在探讨GABA(B)受体激动剂巴氯芬对功能性消化不良(FD)大鼠胃超敏反应的影响及其作用机制。方法：10日龄雄性大鼠每日灌胃0.2mL0.1%碘乙酰胺+2%蔗糖溶液，连续6d。对照组给予2%蔗糖。给予巴氯芬(0.3、1和3 mg kg(-1)bw)或生理盐水治疗8~10周后，检测行为和肌电(EMG)内脏运动反应、不同程度胃扩张时的胃脊神经传入活动和伤害性胃扩张后T8~T10段脊髓背角Fos蛋白的表达。结果：巴氯芬能显著降低新生大鼠的行为反应和EMG反应(1和3 mg kg(-1))，并能显著降低T8和T9节段Fos的表达。但巴氯芬对胃扩张的内脏神经活动无明显影响。与致敏大鼠相比，巴氯芬(3 mg kg(-1))还能显著降低致敏大鼠胃扩张后脊髓Fos的表达。结论与推断：巴氯芬能有效地减轻实验性FD大鼠的疼痛相关反应，可能是通过中枢机制起作用的。这些结果为该药在FD患者中的临床试验提供了依据。
BACKGROUND: The amino acid gamma-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).METHODS: 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.KEY RESULTS: 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.