Involvement of spinal calcitonin gene-related peptide in the development of acute visceral hyperalgesia in the rat
Involvement of spinal calcitonin gene-related peptide in the development of acute visceral hyperalgesia in the rat
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DOI：
10.1046/j.1365-2982.2001.00262.x
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发表时间：
2001-06-01
影响因子：
3.5
通讯作者：
Mayer, EA
中科院分区：
文献类型：
--
作者：
Gschossmann, JM;Coutinho, SV;Mayer, EA
本研究旨在探讨神经肽降钙素基因相关肽（CGRP）在机械性内脏痛觉过敏中的作用。在禁食、清醒的雄性Sprague-Dawley大鼠中进行强直性结肠直肠扩张（CRD）。与有害性CRD相关的内脏反射被确定为连续两次强直性扩张（60 mmHg下10 min）中每一次的收缩次数，这两次扩张被一系列阶段性扩张（以30 s的间隔重复15 s扩张至80 mmHg）分开。CGRP受体拮抗剂h-CGRP（8-37）鞘内（i.t.）（0.03-3 nmol大鼠（-1））或静脉内（i. v.）(20 10 μ g/kg（-1）体重[bw]）对内脏反应的影响。根据先前类似研究的结果选择静脉给药的剂量。此外，还评价了静脉注射CGRP单克隆抗体（6 mg kg（-1）bw）的效果。与基线反应相比，在第二次强直性扩张期间观察到腹部收缩次数显著增加。信息科技应用h-CGRP（8-37）剂量依赖性地减少了第一和第二强直性膨胀期间的腹部收缩次数，在3 nmol的肽浓度下观察到最大效果。静脉注射h-CGRP（8-37）或CGRP抗血清可使第二次强直性扩张引起的内脏反应略有降低，但对结肠顺应性无影响。重复强直性扩张引起的机械性结肠直肠痛觉过敏的发展涉及CGRP的脊髓释放，而CGRP的外周释放仅起次要作用。
This study aimed to characterize the role of the neuropeptide calcitonin gene-related peptide (CGRP) in the development of mechanically induced visceral hyperalgesia. Tonic colorectal distension (CRD) was performed in fasted, conscious male Sprague-Dawley rats. The visceromotor reflex associated with noxious CRD was determined as the number of contractions during each of two consecutive tonic distensions (10 min at 60 mmHg), which were separated by a series of phasic distensions (repeated 15-s distensions to 80 mmHg at 30-s intervals). The effect of the CGRP receptor antagonist h-CGRP(8-37) given intrathecally (i.t.) (0.03-3 nmol rat(-1)) or intravenously (i.v.) (20 mug kg(-1) bodyweight [bw]) on the visceromotor response was evaluated. The dose for i.v. administration was chosen based on previous results from similar studies. In addition, the effect of a CGRP monoclonal antibody (6 mg kg(-1) bw) given intravenously was evaluated. Compared to the baseline response, a significant increase in the number of abdominal contractions was observed during the second tonic distension. The i.t. application of h-CGRP(8-37) dose-dependently reduced the numbers of abdominal contractions both during the first and the second tonic distension period, with a maximum effect observed at a peptide concentration of 3 nmol. Intravenous administration of h-CGRP(8-37) or of the CGRP antiserum produced a small reduction of the visceromotor response induced by the second tonic distension and had no effect on colonic compliance. The development of mechanically induced colorectal hyperalgesia by repeated tonic distension involves the spinal release of CGRP, while peripheral release of CGRP plays only a minor role.