Cupini L M, Costa C, Sarchielli P, Bari M, Battista N, Eusebi P, Calabresi P, Maccarrone M
U.O.C. Neurologia, Dipartimento Cranio Spinale, Ospedale S. Eugenio, Roma, Italy.
Neurobiol Dis. 2008 May;30(2):186-9. doi: 10.1016/j.nbd.2008.01.003. Epub 2008 Feb 1.
Chronic migraine (CM) is frequently associated with medication overuse headache (MOH). The endocannabinoid system plays a role in modulating pain including headache and is involved in the common neurobiological mechanism underlying drug addiction and reward system. Anandamide (AEA) and 2-arachidonoylglycerol are the most biologically active endocannabinoids, which bind to both central and peripheral cannabinoid receptors. The level of AEA in the extracellular space is controlled by cellular uptake via a specific AEA membrane transporter (AMT), followed by intracellular degradation by the enzyme AEA hydrolase (fatty acid amide hydrolase, FAAH). AMT and FAAH have also been characterized in human platelets. We assayed the activity of AMT and of FAAH in platelets isolated from four groups of subjects: MOH, CM without MOH, episodic migraine and controls. AMT and FAAH were significantly reduced in CM and MOH, compared to either controls or episodic migraine group. This latter finding was observed in both males and females with CM and MOH. Changes observed in the biochemical mechanisms degrading endogenous cannabinoids may reflect an adaptative behaviour induced by chronic headache and/or drug overuse.
慢性偏头痛（CM）常与药物过度使用性头痛（MOH）相关。内源性大麻素系统在调节包括头痛在内的疼痛中起作用，并且参与药物成瘾和奖赏系统的常见神经生物学机制。花生四烯乙醇胺（AEA）和2-花生四烯酸甘油酯是生物活性最强的内源性大麻素，它们与中枢和外周大麻素受体结合。细胞外空间中AEA的水平通过特定的AEA膜转运体（AMT）进行细胞摄取来控制，随后由AEA水解酶（脂肪酸酰胺水解酶，FAAH）进行细胞内降解。AMT和FAAH在人血小板中也有特征描述。我们测定了从四组受试者分离出的血小板中AMT和FAAH的活性：MOH、无MOH的CM、发作性偏头痛患者和对照组。与对照组或发作性偏头痛组相比，CM和MOH患者的AMT和FAAH活性显著降低。在患有CM和MOH的男性和女性中均观察到了这一结果。内源性大麻素降解生化机制的变化可能反映了慢性头痛和/或药物过度使用引起的适应性行为。
