Medication overuse headache is estimated to affect 2% of the population, and is ranked in the top 20 most disabling disorders due to its high level of disability. Several therapies used in the treatment of acute migraine are thought to be associated with medication overuse headache, including opioids and triptans. With limited treatment options, it is critical to determine the risk profile of novel therapies prior to their widespread use. The current study explores the potential medication overuse risk of two novel therapeutic drug classes, namely the ditans: 5-HT_1F receptor agonists, and the gepants: calcitonin gene-related peptide receptor antagonists, in a preclinical model of medication overuse. Persistent exposure of mice to the 5-HT_1F agonist LY344864, but not olcegepant produced a significant reduction in hind paw and orofacial mechanical withdrawal thresholds as a surrogate readout of allodynia. In agreement, only LY344864 induced neuroplastic changes in trigeminal sensory afferents, increasing calcitonin gene-related peptide expression and basal trigeminal nociception. Our data highlight a differential medication overuse headache risk profile for the ditan and gepant classes of drugs that has important implications for their clinical use and patient education to help reduce the burden of medication overuse headache.

中文翻译：

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新型抗偏头痛疗法的不同药物过度使用风险。

据估计，药物过度使用性头痛影响着 2% 的人口，并且由于其严重致残性而被列为前 20 名最致残的疾病。用于治疗急性偏头痛的几种疗法被认为与药物过度使用性头痛有关，包括阿片类药物和曲坦类药物。由于治疗选择有限，在广泛使用新疗法之前确定其风险状况至关重要。目前的研究在药物过度使用的临床前模型中探讨了两种新型治疗药物类别的潜在药物过度使用风险，即 ditans：5-HT _{1F受体激动剂和 gepants：降钙素基因相关肽受体拮抗剂。}小鼠持续暴露于 5-HT _1F激动剂 LY344864（而非 olcegepant）会导致后爪和口面部机械退缩阈值显着降低，作为异常性疼痛的替代读数。一致认为，只有 LY344864 诱导三叉神经感觉传入的神经塑性变化，增加降钙素基因相关肽的表达和基础三叉神经伤害感受。我们的数据强调了 ditan 和 gepant 类药物的不同药物过度使用性头痛风险状况，这对其临床使用和患者教育具有重要意义，有助于减轻药物过度使用性头痛的负担。