Sensitization of meningeal nociceptors: inhibition by naproxen
Sensitization of meningeal nociceptors: inhibition by naproxen
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DOI：
10.1111/j.1460-9568.2008.06068.x
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发表时间：
2008-02-01
影响因子：
3.4
通讯作者：
Burstein, Rami
中科院分区：
文献类型：
--
作者：
Levy, Dan;Zhang, Xi-Chun;Burstein, Rami
通过静脉注射非选择性环氧合酶(COX)抑制剂，可以很容易地终止与搏动(表现为外周敏化)和皮肤过敏(表现为中枢敏化)相关的偏头痛发作。有证据表明，非选择性COX抑制也可在体内终止大鼠三叉神经中枢神经元的敏化，这使得我们提出COX抑制剂可能在背角起中枢作用。在本研究中，我们研究了环氧合酶抑制是否也能抑制脑膜伤害性感受器的外周敏感化。在活体三叉神经节的单单位记录中，我们发现静脉注射非选择性COX抑制剂萘普生逆转了预先将硬脑膜暴露于炎性汤(IS)所引起的脑膜伤害性感受器的敏化措施：A单位和C单位的持续活动及其对硬脑膜机械刺激的反应幅度，在IS后增强，在注射NAPROXN后恢复到基线。局部应用萘普生或选择性COX-2抑制剂N-[2-(cyclohexyloxy)-4-nitrophenyl]-methanesulfonamide(NS-398)到A单位和C单位伤害性感受器的硬脑膜感受野，也逆转了神经元对机械刺激硬脑膜的高反应性。这一发现表明，硬脑膜中局部的COX活性可能介导了偏头痛背后的外周敏化。
Migraine attacks associated with throbbing (manifestation of peripheral sensitization) and cutaneous allodynia (manifestation of central sensitization) are readily terminated by intravenous administration of a non-selective cyclooxygenase (COX) inhibitor. Evidence that sensitization of rat central trigeminovascular neurons was also terminated in vivo by non-selective COX inhibition has led us to propose that COX inhibitors may act centrally in the dorsal horn. In the present study, we examined whether COX inhibition can also suppress peripheral sensitization in meningeal nociceptors. Using single-unit recording in the trigeminal ganglion in vivo, we found that intravenous infusion of naproxen, a non-selective COX inhibitor, reversed measures of sensitization induced in meningeal nociceptors by prior exposure of the dura to inflammatory soup (IS): ongoing activity of A delta- and C-units and their response magnitude to mechanical stimulation of the dura, which were enhanced after IS, returned to baseline after naproxen infusion. Topical application of naproxen or the selective COX-2 inhibitor N-[2-(cyclohexyloxy)-4-nitrophenyl]-methanesulfonamide (NS-398) onto the dural receptive field of A delta- and C-unit nociceptors also reversed the neuronal hyper-responsiveness to mechanical stimulation of the dura. The findings suggest that local COX activity in the dura could mediate the peripheral sensitization that underlies migraine headache.