Sustained morphine-induced sensitization and loss of diffuse noxious inhibitory controls in dura-sensitive medullary dorsal horn neurons.
Sustained morphine-induced sensitization and loss of diffuse noxious inhibitory controls in dura-sensitive medullary dorsal horn neurons.
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DOI：
10.1523/jneurosci.3623-09.2009
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发表时间：
2009-12-16
期刊：
影响因子：
--
通讯作者：
Meng ID
中科院分区：
文献类型：
--
作者：
Okada-Ogawa A;Porreca F;Meng ID
过度使用用于治疗偏头痛的药物会产生慢性日常头痛，称为药物过度头痛(MOH)。尽管“过度使用”阿片类药物、曲普坦和非处方药都会产生MOH，但其神经机制仍不清楚。头痛可能是由于刺激支配颅内血管的初级传入神经元，从而激活延髓背角(MDH)神经元而产生的。本研究比较了吗啡处理大鼠和给药大鼠硬脑膜MDH敏感神经元的感受野特性。在记录硬脑膜敏感神经元前6-7天，动物被植入渗透性微泵或颗粒，以持续皮下注射吗啡或载体。与车辆对照组相比，慢性吗啡处理组动物硬脑膜的电和机械激活阈值显著降低。此外，持续的吗啡增加了皮肤接受野的大小。在伴随伤害性热刺激皮肤感受野(通常位于眼部)的过程中，通过将尾巴放在55°C的水中来检查弥漫性伤害抑制对照(DNIC)的存在。DNIC刺激对车辆热诱发活动有显著抑制作用，但对慢性吗啡处理的动物无明显抑制作用。用4%利多卡因灭活慢性吗啡处理动物的延髓头端腹内侧核(RVM)可使DNIC恢复。这些结果与研究表明，患有慢性日常头痛的患者的DNIC丢失是一致的，并可能部分解释了为什么过度使用治疗偏头痛的药物会导致头痛。
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 mini-pumps or pellets for sustained subcutaneous administration of morphine or vehicle 6–7 days prior to 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 (DNIC) was examined by placing the tail in 55°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 (RVM) with 4% lidocaine reinstated DNIC in chronic morphine treated animals. These results are consistent with studies demonstrating a loss of DNIC in patients that suffer from chronic daily headache and may partially explain why overuse of medication used to treat migraine can induce headaches.