Pharmacology Department, Biological Sciences Institute, Federal University of Minas Gerais, Belo Horizonte, Brazil.
NHLI, Imperial College, London, United Kingdom.
Neuropeptides. 2018 Apr;68:43-48. doi: 10.1016/j.npep.2018.01.004. Epub 2018 Feb 1.
This study aimed to assess the potential of calcitonin-gene related peptide (CGRP), a neuropeptide released from sensory nerves, to induce oedema in orofacial tissue.
Wistar rats (150-200 g) anesthetized with isoflurane were injected intraorally with CGRP (100 μl; 8-33 pmol) in the right side of the mouth. The contralateral side was injected with the same volume of physiological saline. Increased cheek thickness (in mm), as a measure of oedema formation, was assayed bilaterally with a digital caliper before (T = 0) and up to 24 h following injection of CGRP. Pretreatment with antagonists (CGRP 10 nmol; pizotifen, 2 mg/kg) was given by intra-oral or subcutaneous injection, 10 or 30 min, respectively, before the inflammatory stimulus. CGRP and CGRP were also injected into the rat hind paw to induce oedema. Data are presented as the mean (±SEM) difference in thickness between the right and the left sides at each time.
Following intra-oral injection, CGRP induced a rapidly developing (5-15 min) and long-lasting (6 h), dose-dependent oedema in the rat cheek, blocked by pre-treatment with CGRP or pizotifen. CGRP induced a smaller oedematogenic effect in the rat hind paw also blocked by the CGRP antagonist. CGRP (16 pmol) potentiated the oedema induced by co-injected substance P (3.7 nmol) and contributed to the oedema following intraoral injection of carrageenan (100 μg). Injection of CGRP alone induced an early but short-lasting oedema.
Local injection of CGRP potently induced oedema in the orofacial tissue of rats which was blocked by a CGRP receptor antagonist. The overall inhibition of carrageenan-induced oedema by CGRP suggests that endogenous CGRP contributes to an oedematogenic response in orofacial tissues.
本研究旨在评估降钙素基因相关肽（CGRP）——一种从感觉神经释放的神经肽——诱导口腔组织水肿的潜力。
异氟烷麻醉的 Wistar 大鼠（150-200g）经口腔内注射 CGRP（100µl；8-33pmol）于右侧口腔。对侧注射相同体积的生理盐水。在注射 CGRP 前（T=0）和注射后 24 小时内，使用数字卡尺双侧检测颊厚度（mm）的增加，作为水肿形成的衡量标准。在炎症刺激前 10 或 30 分钟，通过口腔内或皮下注射 CGRP 10nmol 或 pizotifen（2mg/kg）进行拮抗剂预处理。CGRP 和 CGRP 也被注射到大鼠后爪以诱导水肿。数据以右侧和左侧厚度在每个时间点的平均（±SEM）差异表示。
口腔内注射 CGRP 后，CGRP 诱导了大鼠颊部快速发展（5-15 分钟）和持久（6 小时）、剂量依赖性水肿，该水肿被 CGRP 或 pizotifen 预处理所阻断。CGRP 诱导的大鼠后爪水肿作用较小，也被 CGRP 拮抗剂阻断。CGRP（16pmol）增强了共同注射的 P 物质（3.7nmol）诱导的水肿，并促成了口腔内注射角叉菜胶（100μg）后的水肿。单独注射 CGRP 会引起早期但短暂的水肿。
CGRP 局部注射可强烈诱导大鼠口腔组织水肿，该水肿被 CGRP 受体拮抗剂阻断。CGRP 对卡拉胶诱导的水肿的总体抑制作用表明内源性 CGRP 有助于口腔组织的水肿反应。
