Martino G, Perkins M N
AstraZeneca Research and Development Montreal, Ville St Laurent, Montreal, Quebec, Canada.
Cephalalgia. 2008 Jul;28(7):723-33. doi: 10.1111/j.1468-2982.2008.01582.x. Epub 2008 May 21.
A pharmacological model of migraine is described using ultrasound vocalization (USV) of rats following central inflammation-induced sensitization to tactile stimulation. Central inflammation induced by intracerebroventricular injection of lipopolysaccharide (LPS) increased USV induced by an air current focused on the head and this was abolished by morphine and ketorolac, suggesting a nociceptive component. USV in naive rats were unaffected. Diazepam reduced USV in both inflamed and naive rats. The triptans, zolmitriptan and sumatriptan, both reduced USV in inflamed but not in naive rats, as did dihydroergotamine, and the calcitonin gene-related peptide (CGRP) antagonists alphaCGRP(8-37) and BIBN4096BS. The neurokinin-1 antagonist L-733-060 had no effect in either inflamed or naive rats when given after induction of inflammation, but when given with the LPS it prevented the augmentation of USV. This profile of activity of agents proven to be effective in the clinic suggests this model can be used to predict novel therapeutic agents for migraine.
利用大鼠在中枢炎症诱导的触觉刺激致敏后进行的超声发声（USV），描述了一种偏头痛的药理学模型。脑室内注射脂多糖（LPS）诱导的中枢炎症增加了聚焦于头部的气流诱导的USV，而吗啡和酮咯酸可消除这种增加，提示存在伤害感受成分。未处理大鼠的USV不受影响。地西泮可降低炎症大鼠和未处理大鼠的USV。曲坦类药物佐米曲坦和舒马曲坦以及双氢麦角胺、降钙素基因相关肽（CGRP）拮抗剂αCGRP(8 - 37)和BIBN4096BS均能降低炎症大鼠而非未处理大鼠的USV。神经激肽-1拮抗剂L - 733 - 060在炎症诱导后给予时，对炎症大鼠和未处理大鼠均无影响，但与LPS同时给予时可防止USV增加。这种在临床上已被证明有效的药物活性特征表明，该模型可用于预测偏头痛的新型治疗药物。
