title: Sustained morphine-induced sensitization and loss of diffuse noxious inhibitory controls in dura-sensitive medullary dorsal horn neurons.
abstract: 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.
authors.affiliation: Department of Oral Diagnosis, School of Dentistry, Nihon University, Kanda-Surugadai, Chiyoda-ku, Tokyo 101-8310, Japan.
authors.forename: Akiko
authors.initials: A
authors.lastname: Okada-Ogawa
authors.forename: Frank
authors.initials: F
authors.lastname: Porreca
authors.forename: Ian D
authors.initials: ID
authors.lastname: Meng
mesh_terms: D000818:Animals; D003692:Delayed-Action Preparations / Q000008:administration & dosage; D004388:Dura Mater / Q000187:drug effects / Q000502:physiology*; D008297:Male; D008526:Medulla Oblongata / Q000187:drug effects / Q000502:physiology*; D009020:Morphine / Q000008:administration & dosage*; D009433:Neural Inhibition / Q000187:drug effects / Q000502:physiology*; D010147:Pain Measurement / Q000187:drug effects; D020671:Posterior Horn Cells / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D003692:Delayed-Action Preparations; D009020:Morphine