Department of Pharmacology, University of Arizona College of Medicine, Tucson, AZ, USA.
Ann Neurol. 2010 Mar;67(3):325-37. doi: 10.1002/ana.21897.
Identification of the neural mechanisms underlying medication overuse headache resulting from triptans.
Triptans were administered systemically to rats by repeated intermittent injections or by continuous infusion over 6 days. Periorbital and hind paw sensory thresholds were measured to detect cutaneous allodynia. Immunofluorescent histochemistry was employed to detect changes in peptidic neurotransmitter expression in identified dural afferents. Enzyme-linked immunoabsorbent assay was used to measure calcitonin gene-related peptide (CGRP) levels in blood.
Sustained or repeated administration of triptans to rats elicited time-dependent and reversible cutaneous tactile allodynia that was maintained throughout and transiently after drug delivery. Triptan administration increased labeling for CGRP in identified trigeminal dural afferents that persisted long after discontinuation of triptan exposure. Two weeks after triptan exposure, when sensory thresholds returned to baseline levels, rats showed enhanced cutaneous allodynia and increased CGRP in the blood following challenge with a nitric oxide donor. Triptan treatment thus induces a state of latent sensitization characterized by persistent pronociceptive neural adaptations in dural afferents and enhanced responses to an established trigger of migraine headache in humans.
Triptans represent the treatment of choice for moderate and severe migraine headaches. However, triptan overuse can lead to an increased frequency of migraine headache. Overuse of these medications could induce neural adaptations that result in a state of latent sensitization, which might increase sensitivity to migraine triggers. The latent sensitization could provide a mechanistic basis for the transformation of migraine to medication overuse headache.
确定曲坦类药物过度使用性头痛的神经机制。
通过重复间歇性注射或连续输注 6 天，向大鼠体内系统给予曲坦类药物。测量眶周和后爪感觉阈值，以检测皮肤感觉过敏。采用免疫荧光组织化学方法检测已知硬脑膜传入神经中肽类神经递质表达的变化。酶联免疫吸附试验用于测量血液中降钙素基因相关肽（CGRP）的水平。
持续或重复给予曲坦类药物会引起大鼠产生时间依赖性和可逆性的皮肤触觉过敏，这种过敏在药物输送期间和之后短暂持续存在。曲坦类药物给药增加了已鉴定的三叉神经硬脑膜传入神经中 CGRP 的标记，这种标记在停止曲坦类药物暴露后仍持续很长时间。在曲坦类药物暴露 2 周后，当感觉阈值恢复到基线水平时，大鼠在接受一氧化氮供体挑战时表现出增强的皮肤感觉过敏和血液中 CGRP 增加。因此，曲坦类药物治疗会导致潜伏致敏状态，其特征是硬脑膜传入神经中持续存在促伤害性神经适应，以及对人类偏头痛头痛的既定触发因素的反应增强。
曲坦类药物是治疗中度和重度偏头痛头痛的首选药物。然而，曲坦类药物的过度使用会导致偏头痛头痛的频率增加。这些药物的过度使用可能会引起神经适应，导致潜伏致敏状态，从而增加对偏头痛触发因素的敏感性。潜伏致敏状态可能为偏头痛向药物过度使用性头痛的转变提供机制基础。
