The spinal network coordinating locomotion is comprised of a core of glutamate and glycine interneurons. This network is modulated by several transmitter systems including spinal GABA interneurons. The purpose of this study is to explore the contribution of GABAergic neurons to the regulation of locomotor burst frequency in the lamprey model. Using gabazine, a competitive GABAA antagonist more specific than bicuculline, the goal was to provide a detailed analysis of the influence of an endogenous activation of GABAA receptors on fictive locomotion, as well as their possible interaction with GABAB and involvement of GABAC receptors. During N-methyl-D-aspartate (NMDA)-induced fictive locomotion (ventral root recordings in the isolated spinal cord), gabazine (0.1-100 microM) significantly increased the burst rate up to twofold, without changes in regularity or "burst quality." Gabazine had a proportionately greater effect at higher initial burst rates. Picrotoxin (1-7.5 microM), a less selective GABAA antagonist, also produced a pronounced increase in frequency, but at higher concentrations, the rhythm deteriorated, likely due to the unspecific effects on glycine receptors. The selective GABAB antagonist CGP55845 also increased the frequency, and this effect was markedly enhanced when combined with the GABAA antagonist gabazine. The GABAC antagonist (1,2,5,6-tetrahydropyridine-4-yl)methylphosphinic acid (TPMPA) had no effect on locomotor bursting. Thus the spinal GABA system does play a prominent role in burst frequency regulation in that it reduces the burst frequency by < or =50%, presumably due to presynaptic and soma-dendritic effects documented previously. It is not required for burst generation, but acts as a powerful modulator.
Objective The aim of the present study was to examine the effect of chronic morphine exposure on diffuse noxious inhibitory controls in a large population of neurons throughout the medullary dorsal horn, as assessed using immunocytochemistry for c-Fos protein. Background Overuse of medications, including the opioids, to treat migraine headache can lead to progressively more frequent headaches. In addition, chronic daily headache sufferers and chronic opioid users both lack the inhibition of pain produced by noxious stimulation of a distal body region, often referred to as diffuse noxious inhibitory controls. Methods In urethane anesthetized rats, Fos-positive neurons were quantified in chronic morphine and vehicle treated animals following 52°C noxious thermal stimulation of the cornea with and without the application of a spatially remote noxious stimulus (placement of the tail in 55°C water). Results When compared to chronic morphine treated animals that did not receive the spatially remote noxious stimulus, chronic morphine treated animals given corneal stimulation along with the spatially remote noxious stimulus demonstrated a 163% increase (p<0.05) in the number of Fos-positive neurons in the superficial laminae of the medullary dorsal horn and a 682% increase (p<0.01) in deep laminae that was restricted to the side ipsilateral to the applied stimulus. In contrast, no significant difference was found in Fos-like immunoreactivity in vehicle treated animals given concurrent cornea and tail stimulation or only cornea stimulation in either superficial or deep laminae. Conclusions It is proposed that an increase in descending facilitation and subsequent loss of diffuse noxious inhibitory controls contributes to the development of medication overuse headache.
The forces of internationalization have been central to the Republic of Ireland's dramatic transformation during the past four decades. The political, social, and economic changes brought about by membership in the European Union (EU) have been especially significant. Ireland has been described s a “Celtic Tiger” whose stellar economic growth rate during the past decade has given it one of the highest per capita GDP levels in the EU. Much of this success has resulted from imaginative and dynamic programs developed b y Irish political and administrative leaders. Ireland's good working relationship with the United Kingdom has enabled the two governments to achieve significant progress in the search for peace in Northern Ireland, whatever setbacks may occur during the long term evolution of this process.
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