Ness T J, Gebhart G F
Department of Pharmacology, College of Medicine, University of Iowa, Iowa City 52242.
Brain Res. 1988 May 31;450(1-2):153-69. doi: 10.1016/0006-8993(88)91555-7.
This report presents evidence that colorectal distension is a reproducible, reliable, valid, noxious visceral stimulus that can be used in studies performed in awake, unanesthetized, unrestrained rats. Colorectal distension produces aversive behavior and cardiovascular and visceromotor responses which are quantifiable, reliable, reproducible and useful for inter- and intra-animal studies. The cardiovascular response, a pressor response with tachycardia, is graded and thought to be due to an increase in sympathetic outflow coupled with removal of vagal tone since it is attenuated in a dose-dependent way by atropine, propranolol, phentolamine, chlorisondamine and adrenal demedullation. The visceromotor response is a contraction of abdominal and hindlimb musculature. The distending pressure threshold for the visceromotor response (22.4 +/- 0.9 mm Hg) is significantly greater than that necessary to evoke a non-nociceptive response, relaxation of the anal sphincters (13.2 +/- 0.7 mm Hg). Both the cardiovascular and visceromotor responses act via brainstem loops since both are vigorous in decerebrate (midcollicular) but not spinalized (C1 or T6) rats. Anesthetics attenuated (alphaxalone/alphadolone, ketamine) or reversed (urethane, pentobarbital, alpha-chloralose) the cardiovascular responses to colorectal distension and attenuated (alphaxalone/alphadolone) or abolished (others listed above) the visceromotor response. Both morphine (systemic and intrathecal) and clonidine (intrathecal) produced a dose-dependent inhibition of both the cardiovascular and visceromotor responses to colorectal distension. Thus, in the awake, unrestrained rat, the cardiovascular and visceromotor responses to colorectal distension are quantifiable, reliable and reproducible signs of acute visceral nociception.
本报告提供的证据表明，结肠扩张是一种可重复、可靠、有效的伤害性内脏刺激，可用于在清醒、未麻醉、未束缚的大鼠身上进行的研究。结肠扩张会产生厌恶行为以及心血管和内脏运动反应，这些反应是可量化、可靠、可重复的，并且对动物间和动物内研究有用。心血管反应是一种伴有心动过速的升压反应，呈分级变化，被认为是由于交感神经输出增加以及迷走神经张力消除所致，因为它会被阿托品、普萘洛尔、酚妥拉明、氯筒箭毒碱和肾上腺髓质摘除以剂量依赖的方式减弱。内脏运动反应是腹部和后肢肌肉组织的收缩。内脏运动反应的扩张压力阈值（22.4±0.9毫米汞柱）明显高于引起非伤害性反应（肛门括约肌松弛，13.2±0.7毫米汞柱）所需的压力阈值。心血管和内脏运动反应均通过脑干环路起作用，因为在去大脑（中脑水平）大鼠中这两种反应都很强烈，但在脊髓横断（C1或T6）大鼠中则不然。麻醉剂会减弱（阿法沙龙/阿法多龙、氯胺酮）或逆转（乌拉坦、戊巴比妥、α-氯醛糖）对结肠扩张的心血管反应，并减弱（阿法沙龙/阿法多龙）或消除（上述其他药物）内脏运动反应。吗啡（全身给药和鞘内给药）和可乐定（鞘内给药）均对结肠扩张的心血管和内脏运动反应产生剂量依赖性抑制。因此，在清醒、未束缚的大鼠中，对结肠扩张的心血管和内脏运动反应是急性内脏痛觉的可量化、可靠且可重复的指标。
