Triptan-induced latent sensitization: a possible basis for medication overuse headache.
Triptan-induced latent sensitization: a possible basis for medication overuse headache.
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DOI：
10.1002/ana.21897
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发表时间：
2010-03
影响因子：
11.2
通讯作者：
Porreca F
中科院分区：
文献类型：
--
作者：
De Felice M;Ossipov MH;Wang R;Lai J;Chichorro J;Meng I;Dodick DW;Vanderah TW;Dussor G;Porreca F
曲坦类药物导致药物过度使用头痛的神经机制的鉴定。在6天内通过重复间歇注射或连续输注向大鼠全身给予曲坦类药物。测量眶周和后爪感觉阈值以检测皮肤异常性疼痛。免疫荧光组织化学检测肽类神经递质表达的变化，在确定的硬膜传入。采用酶联免疫吸附法测定血中降钙素基因相关肽（CGRP）水平。持续或重复给予大鼠曲坦类药物引起时间依赖性和可逆性皮肤触觉异常性疼痛，在药物递送后持续和短暂维持。给予曲坦可增加三叉神经硬脑膜传入纤维中CGRP的标记，这种标记在曲坦暴露停止后持续很长时间。曲坦暴露后两周，当感觉阈值恢复到基线水平时，大鼠表现出增强的皮肤异常性疼痛和增加的CGRP在血液中与一氧化氮供体的挑战。因此，Triptan治疗诱导了一种潜伏性致敏状态，其特征在于硬脑膜传入中持续的原伤害性神经适应和对人类偏头痛的既定触发因素的增强反应。曲坦类药物是治疗中度和重度偏头痛的首选药物。然而，曲坦过度使用可导致偏头痛的频率增加。过度使用这些药物可能会诱导神经适应，导致潜在的敏化状态，这可能会增加对偏头痛触发因素的敏感性。这种潜在的致敏作用可能为偏头痛向药物过度使用性头痛的转化提供了机制基础。
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.
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影响因子：
7.4
作者：
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通讯作者：
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