Plourde V, St-Pierre S, Quirion R
Neurobiology and Digestive Motility Laboratory, André-Viallet Clinical Research Center, University of Montreal, Quebec, Canada.
Am J Physiol. 1997 Jul;273(1 Pt 1):G191-6. doi: 10.1152/ajpgi.1997.273.1.G191.
The role of calcitonin gene-related peptide (CGRP) on colorectal distension-induced visceral pain was investigated in conscious rats. Intracolonic administration of acetic acid (0.6%) resulted in a significantly increased number of abdominal contractions in response to colorectal balloon distension from 5.8 +/- 1.2 in controls to 16.6 +/- 1.0 in acetic acid-treated animals (P < 0.05), evidencing sensitization of visceral afferent pathways and subsequently visceral hyperalgesia. This sensitization phenomenon was not observed in animals previously treated with systemic capsaicin. Likewise, in animals not treated with capsaicin, use of an intravenous antagonist for CGRP [human CGRP-(8-37)], completely reversed the sensitizing effects of acetic acid. Furthermore, intravenous administration of CGRP dose dependently increased the number of abdominal contractions in response to colorectal distension from 3.0 +/- 1.1 (CGRP 250 ng) to 17.0 +/- 1.2 (CGRP 500 ng, P < 0.05), as previously observed in acetic acid-treated animals. Finally, intrathecal administration of hCGRP-(8-37) (mid-lumbar) also resulted in a total dose-dependent reversal of CGRP (500 ng) or acetic acid-induced visceral hypersensitivity. These results demonstrate that CGRP plays a major role in this model of visceral afferent nerve sensitization from gastrointestinal origin.
在清醒大鼠中研究了降钙素基因相关肽（CGRP）对结肠扩张诱导的内脏痛的作用。结肠内给予乙酸（0.6%）导致对结肠球囊扩张的腹部收缩次数显著增加，从对照组的5.8±1.2次增加到乙酸处理动物的16.6±1.0次（P<0.05），证明内脏传入通路致敏以及随后的内脏痛觉过敏。在用全身性辣椒素预处理的动物中未观察到这种致敏现象。同样，在未用辣椒素处理的动物中，使用CGRP的静脉拮抗剂[人CGRP-(8-37)]可完全逆转乙酸的致敏作用。此外，静脉注射CGRP可使对结肠扩张的腹部收缩次数剂量依赖性增加，从3.0±1.1次（CGRP 250 ng）增加到17.0±1.2次（CGRP 500 ng，P<0.05），正如先前在乙酸处理的动物中所观察到的。最后，鞘内注射hCGRP-(8-37)（腰段中部）也导致CGRP（500 ng）或乙酸诱导的内脏超敏反应完全剂量依赖性逆转。这些结果表明，CGRP在这种胃肠道源性内脏传入神经致敏模型中起主要作用。
