Sustained Morphine-Induced Sensitization and Loss of Diffuse Noxious Inhibitory Controls in Dura-Sensitive Medullary Dorsal Horn Neurons

被引:65
作者
Okada-Ogawa, Akiko [3 ]
Porreca, Frank [2 ]
Meng, Ian D. [1 ]
机构
[1] Univ New England, Dept Physiol, Coll Osteopath Med, Biddeford, ME 04005 USA
[2] Univ Arizona, Hlth Sci Ctr, Coll Med, Dept Pharmacol, Tucson, AZ 85724 USA
[3] Nihon Univ, Sch Dent, Dept Oral Diag, Chiyoda Ku, Tokyo 1018310, Japan
关键词
ROSTRAL VENTROMEDIAL MEDULLA; MEDICATION OVERUSE HEADACHE; SPINAL TRIGEMINAL NUCLEUS; GENE-RELATED PEPTIDE; OPIOID ANTINOCICEPTIVE TOLERANCE; TONIC DESCENDING FACILITATION; CANNABINOID RECEPTOR AGONIST; MENINGEAL SENSORY NEURONS; INDUCED HYPERALGESIA; SUBSTANCE-P;
D O I
10.1523/JNEUROSCI.3623-09.2009
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
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 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.
引用
收藏
页码:15828 / 15835
页数:8
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