Department of Oral Diagnosis, School of Dentistry, Nihon University, Kanda-Surugadai, Chiyoda-ku, Tokyo 101-8310, Japan.
J Neurosci. 2009 Dec 16;29(50):15828-35. doi: 10.1523/JNEUROSCI.3623-09.2009.
Overuse of medications used to treat migraine headache can produce a chronic daily headache, termed medication overuse headache (MOH). Although "overuse" of opioids, triptans, and over-the-counter analgesics can all produce MOH, the neuronal mechanisms remain unknown. Headache pain is likely to be produced by stimulation of primary afferent neurons that innervate the intracranial vasculature and the resulting activation of medullary dorsal horn (MDH) neurons. The present study compared the receptive field properties of MDH dura-sensitive neurons in rats treated with morphine to those given vehicle. Animals were implanted with osmotic minipumps or pellets for sustained subcutaneous administration of morphine or vehicle 6-7 d before recording from dura-sensitive neurons. Electrical and mechanical activation thresholds from the dura were significantly lower in chronic morphine-treated animals when compared to vehicle controls. In addition, sustained morphine increased the cutaneous receptive field sizes. The presence of diffuse noxious inhibitory controls (DNICs) was examined by placing the tail in 55 degrees C water during concomitant noxious thermal stimulation of the cutaneous receptive field, usually located in the ophthalmic region. The DNIC stimulus produced significant inhibition of heat-evoked activity in vehicle- but not chronic morphine-treated animals. Inactivation of the rostral ventromedial medulla with 4% lidocaine reinstated DNICs in chronic morphine-treated animals. These results are consistent with studies demonstrating a loss of DNICs in patients that suffer from chronic daily headache and may partially explain why overuse of medication used to treat migraine can induce headaches.
过度使用治疗偏头痛的药物可能会导致慢性每日头痛，称为药物过度使用性头痛（MOH）。虽然“过度”使用阿片类药物、曲坦类药物和非处方止痛药都可能导致 MOH，但神经元机制仍不清楚。头痛可能是由支配颅内血管的初级传入神经元的刺激引起的，进而激活延髓背角（MDH）神经元。本研究比较了接受吗啡治疗和给予载体的大鼠 MDH 硬脑膜敏感神经元的感受野特性。动物在记录硬脑膜敏感神经元之前 6-7 天接受持续皮下给予吗啡或载体的渗透微型泵或微球治疗。与载体对照组相比，慢性吗啡处理的动物的硬脑膜电和机械激活阈值显着降低。此外，持续的吗啡增加了皮肤感受野的大小。通过在同时对皮肤感受野进行疼痛热刺激的情况下将尾巴放在 55°C 水中来检查弥漫性伤害性抑制控制（DNIC）的存在，通常位于眼部区域。DNIC 刺激在载体处理的动物中但不在慢性吗啡处理的动物中显着抑制了热诱发的活动。用 4%利多卡因使头端腹内侧髓质失活，使慢性吗啡处理的动物中的 DNIC 恢复。这些结果与证明患有慢性每日头痛的患者中 DNIC 丧失的研究一致，并且可能部分解释了为什么过度使用治疗偏头痛的药物会引起头痛。
