Tassorelli Cristina, Greco Rosaria, Armentero Marie Therèse, Blandini Fabio, Sandrini Giorgio, Nappi Giuseppe
IRCCS C. Mondino Institute of Neurology Foundation, Pavia, Italy.
Int Rev Neurobiol. 2007;82:373-82. doi: 10.1016/S0074-7742(07)82020-4.
Cyclooxygenase-2 (COX-2) may increase prostaglandin E(2) (PGE(2)) production in central nervous system (CNS) and contribute to the severity of pain responses in inflammatory pain. In this chapter, we sought to evaluate the possible role of COX-2 induction and prostaglandins (PGs) synthesis within neuronal areas proposed to be involved in migraine genesis in the animal model of migraine based on the administration of systemic nitroglycerin (NTG). Male Sprague-Dawley rats were injected with NTG (10mg/kg, i.p.) or vehicle and sacrificed 2 and 4h later. The hypothalamus and the lower brain stem were dissected out and utilized for the evaluation of COX-2 expression by means of Western blotting and for the determination of PGE(2) levels by means of ELISA immunoassay. COX-2 expression increased in the hypothalamus at 2h and in the lower brain stem at 4h. PGE(2) levels showed an opposite pattern of change with a decrease in PGE(2) levels at 2h in the hypothalamus and an increase at 4h in the lower brain stem. These data support the hypothesis that NTG administration is capable of activating the COX-2 pathway within cerebral areas. This activity may explain the pronociceptive effect of NTG described in animal and human models of pain. Most importantly, these findings point to mediators and areas that may be relevant for migraine pathogenesis and treatment.
环氧化酶-2（COX-2）可能会增加中枢神经系统（CNS）中前列腺素E2（PGE2）的生成，并加重炎症性疼痛中疼痛反应的严重程度。在本章中，我们试图基于全身给予硝酸甘油（NTG）的偏头痛动物模型，评估COX-2诱导和前列腺素（PGs）合成在推测参与偏头痛发病机制的神经元区域内可能发挥的作用。雄性Sprague-Dawley大鼠注射NTG（10mg/kg，腹腔注射）或赋形剂，并于2小时和4小时后处死。取出下丘脑和低位脑干，通过蛋白质印迹法评估COX-2表达，并通过ELISA免疫测定法测定PGE2水平。COX-2表达在2小时时在下丘脑增加，在4小时时在低位脑干增加。PGE2水平呈现相反的变化模式，下丘脑在2小时时PGE2水平降低，低位脑干在4小时时升高。这些数据支持以下假设：给予NTG能够激活脑区内的COX-2途径。这种活性可能解释了在动物和人类疼痛模型中所描述的NTG的促痛作用。最重要的是，这些发现指出了可能与偏头痛发病机制和治疗相关的介质和区域。
