Headache Science Centre, IRCCS National Neurological Institute C. Mondino Foundation, University of Pavia, Via Mondino, 2, 27100 Pavia, Italy.
J Headache Pain. 2011 Apr;12(2):177-83. doi: 10.1007/s10194-010-0274-4. Epub 2011 Feb 18.
Systemic nitroglycerin (NTG) produces spontaneous-like migraine attacks in migraine sufferers and induces a condition of hyperalgesia in the rat 4 h after its administration. Endocannabinoid system seems to be involved in the modulation of NTG-induced hyperalgesia, and probably, in the pathophysiological mechanisms of migraine. In this study, the analgesic effect of anandamide (AEA) was evaluated by means of the formalin test, performed in baseline conditions and following NTG-induced hyperalgesia in male Sprague-Dawley rats. AEA was administered 30 min before the formalin injection. In addition, the effect of AEA (administered 30 min before NTG injection) was investigated on NTG-induced Fos expression and evaluated 4 h following NTG injection. AEA induced a significant decrease in the nociceptive behavior during both phases of the formalin test in the animals treated with vehicle, while it abolished NTG-induced hyperalgesia during the phase II. Pre-treatment with AEA significantly reduced the NTG-induced neuronal activation in nucleus trigeminalis caudalis, confirming the results obtained in our previous study, and in area postrema, while the same treatment induced an increase of Fos expression in paraventricular and supraoptic nuclei of the hypothalamus, parabrachial nucleus, and periaqueductal grey. The study confirms that a dysfunction of the endocannabinoid system may contribute to the development of migraine attacks and that a pharmacological modulation of CB receptors can be useful for the treatment of migraine pain.
系统性硝酸甘油（NTG）会在偏头痛患者中引发类似自发性偏头痛发作，并在给药后 4 小时诱导大鼠产生痛觉过敏状态。内源性大麻素系统似乎参与了 NTG 诱导的痛觉过敏的调节，并且可能参与了偏头痛的病理生理机制。在这项研究中，通过在基线条件下和 NTG 诱导的痛觉过敏后进行福尔马林测试，评估了大麻素（AEA）的镇痛作用，在雄性 Sprague-Dawley 大鼠中进行。AEA 在福尔马林注射前 30 分钟给药。此外，还研究了 AEA（在 NTG 注射前 30 分钟给药）对 NTG 诱导的 Fos 表达的影响，并在 NTG 注射后 4 小时进行了评估。在给予载体的动物中，AEA 显著降低了福尔马林测试的两个阶段中的疼痛行为，而在第二阶段中消除了 NTG 诱导的痛觉过敏。AEA 的预处理显著减少了 NTG 诱导的三叉神经尾核中的神经元激活，证实了我们之前研究中的结果，并在后穹窿和孤束核中减少了神经元激活，而相同的处理在下丘脑室旁核和视上核、臂旁核和中脑导水管周围灰质中诱导了 Fos 表达的增加。该研究证实，内源性大麻素系统的功能障碍可能导致偏头痛发作的发展，并且 CB 受体的药理学调节可能对偏头痛疼痛的治疗有用。
