Profound reduction of somatic and visceral pain in mice by intrathecal administration of the anti-migraine drug, sumatriptan.
Profound reduction of somatic and visceral pain in mice by intrathecal administration of the anti-migraine drug, sumatriptan.
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DOI：
10.1016/j.pain.2008.06.002
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发表时间：
2008-10-31
期刊：
影响因子：
7.4
通讯作者：
Ahn AH
中科院分区：
文献类型：
--
作者：
Nikai T;Basbaum AI;Ahn AH
舒马曲坦和其他曲坦类药物靶向5-羟色胺受体亚型1B、1D和1F（5-HT 1B/D/F），并被广泛用于治疗偏头痛。曲坦类的抗偏头痛作用已被假定在多个靶点，在脑内以及在三叉神经“疼痛感觉”纤维的中枢和外周末端。然而，由于曲坦类受体也位于全身的“痛觉”传入神经上，令人惊讶的是曲坦类药物仅能减轻人类的偏头痛和动物的实验性颅痛。在这里，我们测试的假设，舒马曲坦确实可以减少非颅，躯体和内脏疼痛的小鼠行为模型。因为舒马曲坦必须穿过血脑屏障才能到达脊髓中的躯体传入末梢，我们比较了全身性舒马曲坦和直接脊髓（鞘内）舒马曲坦。急性伤害性阈值不改变舒马曲坦预处理，无论路线。然而，在持续性炎性疼痛的行为模型中，我们发现鞘内注射舒马曲坦具有深刻的抗痛觉过敏作用，而不是全身性的。相比之下，舒马曲坦在神经性疼痛的实验模型中完全无效。鞘内注射舒马曲坦对小鼠炎性疼痛的显著活性提高了曲坦类药物除了头痛之外还有更广泛的治疗适应症的可能性。
Sumatriptan and the other triptan drugs target the serotonin receptor subtypes1B, 1D, and 1F (5-HT1B/D/F), and are prescribed widely in the treatment of migraine. An anti-migraine action of triptans has been postulated at multiple targets, within the brain and at both the central and peripheral terminals of trigeminal “pain-sensory” fibers. However, as triptan receptors are also located on “pain-sensory” afferents throughout the body, it is surprising that triptans only reduce migraine pain in humans, and experimental cranial pain in animals. Here we tested the hypothesis that sumatriptan can indeed reduce non-cranial, somatic and visceral pain in behavioral models in mice. Because sumatriptan must cross the blood brain barrier to reach somatic afferent terminals in the spinal cord, we compared systemic to direct spinal (intrathecal) sumatriptan. Acute nociceptive thresholds were not altered by sumatriptan pre-treatment, regardless of route. However, in behavioral models of persistent inflammatory pain, we found a profound anti-hyperalgesic action of intrathecal, but not systemic, sumatriptan. By contrast, sumatriptan was completely ineffective in an experimental model of neuropathic pain. The pronounced activity of intrathecal sumatriptan against inflammatory pain in mice raises the possibility that there is a wider spectrum of therapeutic indications for triptans beyond headache.
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影响因子：
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