Fan Shanghua, Xiao Zheman, Zhu Fan, He Xiaohua, Lu Zuneng
Department of Neurology, Renmin Hospital of Wuhan UniversityJiefang Road 238, Wuhan 430060, Hubei, PR China.
Department of Medical Microbiology, School of Medicine, Wuhan UniversityWuhan 430071, Hubei, PR China.
Am J Transl Res. 2017 May 15;9(5):2286-2295. eCollection 2017.
A bi-directional relationship between epilepsy and migraine has been widely reported in epidemiological and clinical studies, but the mechanisms of interaction between these disorders have not been fully examined using animal models. The aim of the present study was to develop a new comorbidity model of migraine and epilepsy. Nociception was induced by applying an inflammatory soup to the dura mater; this procedure resulted in nociception similar to that expressed in inflammatory disorders such as migraine. We showed that nociceptive behaviors (head rubbing, including with the forepaws and hindpaws) were significantly enhanced in comorbidity rats compared to sham-operation (Sham) rats, and these nociceptive behaviors were correlated with epilepsy-like behaviors. The plasma levels of calcitonin gene-related peptide (CGRP) significantly increased in the migraine group compared with the sham group, but CGRP did not further increase in comorbidity rats compared with migraine rats. C-Fos immunoreactive area values were higher in the comorbidity group than in the migraine group in the trigeminal nucleus caudalis (Sp5C) area (P<0.05). There was no significant difference in HSP70 expression between the comorbidity group and the epilepsy group. The expression of brain-derived neurotrophic factor (BDNF) in the CA3 area of the hippocampus in the comorbidity group was significantly higher than that in the epilepsy group according to the immunohistochemical test (P<0.05). In conclusion, our findings indicate that pilocarpine-induced epilepsy exacerbates inflammatory nociception, which can aggravate seizure severity. Moreover, we established a new comorbidity model for migraine and epilepsy.
癫痫与偏头痛之间的双向关系已在流行病学和临床研究中得到广泛报道，但这些疾病之间相互作用的机制尚未通过动物模型进行充分研究。本研究的目的是建立一种偏头痛和癫痫的新共病模型。通过向硬脑膜施加炎性介质诱导伤害感受；该程序导致的伤害感受类似于偏头痛等炎性疾病中表现出的伤害感受。我们发现，与假手术（Sham）大鼠相比，共病大鼠的伤害感受行为（包括用前爪和后爪摩擦头部）显著增强，并且这些伤害感受行为与癫痫样行为相关。与假手术组相比，偏头痛组降钙素基因相关肽（CGRP）的血浆水平显著升高，但与偏头痛大鼠相比，共病大鼠的CGRP水平没有进一步升高。在三叉神经尾核（Sp5C）区域，共病组的C-Fos免疫反应面积值高于偏头痛组（P<0.05）。共病组与癫痫组之间HSP70表达无显著差异。免疫组织化学检测显示，共病组海马CA3区脑源性神经营养因子（BDNF）的表达明显高于癫痫组（P<0.05）。总之，我们的研究结果表明，毛果芸香碱诱导的癫痫会加剧炎性伤害感受，进而加重癫痫发作的严重程度。此外，我们建立了一种偏头痛和癫痫的新共病模型。
