Sarrouilhe D, Dejean C
Institut de physiologie et de biologie cellulaire, FRE CNRS 3511, université de Poitiers, 40 avenue du Recteur-Pineau, Poitiers cedex, France.
Pathol Biol (Paris). 2012 Dec;60(6):392-8. doi: 10.1016/j.patbio.2012.04.002. Epub 2012 May 25.
Migraine is a common, recurrent and disabling primary headache disorder, which affects up to 20% of the population. About a third of patients with migraine have attacks with aura, a focal neurological disturbance that manifests itself as visual, sensitive or motor symptoms. Cortical spreading depression, a wave of electrical activity that moves across the cerebral cortex through neuronal-glial cell gap junctions, would be involved in the triggering of migraine aura. Moreover, cortical spreading depression activates perivascular trigeminal afferents in the neocortex, that through central and peripheral reflex, cause inflammatory reaction in the meninges to generate the headache. Tonabersat, a novel benzopyran compound, was selected for clinical trial on the basis of its inhibitory activity on cortical spreading depression and neurogenic inflammation in animal models of migraine. Moreover, tonabersat inhibited trigeminal ganglion neuronal-glial cell gap junctions, suggesting that this compound could prevent peripheral sensitization within the ganglion. In clinical trial, tonabersat showed a preventive effect on attacks of migraine with aura but had no efficacy on non-aura attacks and in the acute treatment of migraine. In conclusion, neuronal-glial cell gap junctional intercellular communication seems to be involved in the pathophysiology of migraine with aura and is emerging as a new promising therapeutic target for prophylactic treatment of patients with chronic attacks.
偏头痛是一种常见的、复发性且致残的原发性头痛疾病，影响着高达20%的人群。约三分之一的偏头痛患者发作时伴有先兆，这是一种局灶性神经功能障碍，表现为视觉、感觉或运动症状。皮层扩散性抑制是一种通过神经元 - 胶质细胞缝隙连接在大脑皮层移动的电活动波，它可能参与偏头痛先兆的触发。此外，皮层扩散性抑制激活新皮层中的血管周围三叉神经传入纤维，这些纤维通过中枢和外周反射，引起脑膜的炎症反应以产生头痛。托纳贝萨特是一种新型苯并吡喃化合物，基于其在偏头痛动物模型中对皮层扩散性抑制和神经源性炎症的抑制活性而被选入临床试验。此外，托纳贝萨特抑制三叉神经节神经元 - 胶质细胞缝隙连接，表明该化合物可预防神经节内的外周敏化。在临床试验中，托纳贝萨特对伴有先兆的偏头痛发作显示出预防作用，但对无先兆发作和偏头痛的急性治疗无效。总之，神经元 - 胶质细胞缝隙连接细胞间通讯似乎参与了伴有先兆偏头痛的病理生理学过程，并正成为慢性发作患者预防性治疗的一个新的有前景的治疗靶点。
