Fasting is a physiological stimulus of vagus-mediated enhancement of nociception in the female rat
Fasting is a physiological stimulus of vagus-mediated enhancement of nociception in the female rat
复制标题
DOI：
10.1016/s0306-4522(03)00136-2
复制
发表时间：
2003-01-01
期刊：
影响因子：
3.3
通讯作者：
Levine, JD
中科院分区：
文献类型：
--
作者：
Khasar, SG;Reichling, DB;Levine, JD
迷走神经通过依赖性腺激素和肾上腺髓质的机制来调节伤害性感觉。在目前的研究中，我们验证了这样的假设，即这种调节是由对横隔膜下迷走神经支配的结构的生理刺激动态控制的。具体地说，剥夺食物(禁食)被用来增加隔膜下迷走神经的活动，实验主要在雌性大鼠身上进行，因为我们之前的观察表明，雌性大鼠的基线活动低于雄性大鼠。与假设一致的是，禁食48小时后，雌性大鼠在福尔马林测试中表现出更多的伤害行为。相比之下，禁食对福尔马林诱发的雄性大鼠伤害行为没有影响。禁食对伤害性感觉的影响似乎是由迷走神经介导的，因为它是通过隔膜下迷走神经切断术来防止的。同样类似于之前所描述的迷走神经介导的调节，雌性大鼠的禁食效应被性腺切除或肾上腺髓质切除所阻断，而去性腺的雌性大鼠用17β-雌二醇替代激素恢复了禁食的效果。在禁食对伤害性感受的影响中，葡萄糖代谢的降低显然没有起到明显的作用，因为在整个禁食期间，当饮用水中提供5%的葡萄糖时，这种影响没有变化。另一方面，通过注入凡士林来增加胃的体积含量(不提供营养)显著减弱了福尔马林反应间期期间禁食的影响，这表明减少肠膨胀，可能是减少运动，在禁食诱导的伤害性增强中起重要作用。这些结果表明，禁食是迷走神经介导的痛觉调制通路的生理激活剂。这表明，特别是在女性中，肠道扩张和运动的自然周期性变化可能控制着正在进行的迷走神经介导的有机体伤害性敏感性的调节。(C)2003年IBRO。爱思唯尔科学有限公司出版。版权所有。
The vagus nerve modulates nociception by a mechanism dependent upon gonadal hormones and the adrenal medulla. In the present study we tested the hypothesis that this modulation is dynamically controlled by physiological stimulation of structures innervated by the subdiaphragmatic vagus. Specifically, food deprivation (fasting) was employed to increase activity in the subdiaphragmatic vagus, and the experiments were performed mainly in female rats because our previous observations suggested that baseline activity in the pathway is lower in females than in males. Consistent with the hypothesis, after a 48-h fast, female rats exhibited increased nociceptive behavior in the formalin test. In contrast, fasting had no effect on formalin-evoked nociceptive behavior in male rats. The fasting-induced effect on nociception appears to be mediated by the vagus nerve since it is prevented by subdiaphragmatic vagotomy. Also similar to the previously characterized vagus-mediated modulation, the effect of fasting in the female is blocked by gonadectomy or adrenal medullectomy, and hormone replacement with 17beta-estradiol in gonadectomized female rats restored the effect of fasting. Decreased glucose metabolism apparently does not play a significant role in the effect of fasting on nociception, since the effect was unchanged when 5% glucose was provided in the drinking water throughout the fasting period. On the other hand, increasing the bulk content of the stomach (without providing nutrients) by infusion of petrolatum significantly attenuated the effect of fasting during the interphase period of the formalin response, suggesting that decreased gut distention, and possibly motility, are important in fasting-induced enhancement of nociception.These results indicate that fasting is a physiological activator of the vagus-mediated pain modulation pathway. This suggests the possibility that, especially in females, natural periodic changes in gut distention and motility may control an ongoing vagus-mediated adjustment in the organism's nociceptive sensitivity. (C) 2003 IBRO. Published by Elsevier Science Ltd. All rights reserved.