PMID: 11323134Apr 27, 2001Paper

Activation of brainstem N-methyl-D-aspartate receptors is required for the analgesic actions of morphine given systemically

Pain
M M HeinricherE E Jobst

Abstract

The analgesic actions of opioids are in large part mediated by activation of brainstem pain modulating neurons that depress nociceptive transmission at the level of the dorsal horn. The present study was designed to characterize the contribution of N-methyl-D-aspartate (NMDA)- and non-NMDA-mediated excitatory transmission within the rostral ventromedial medulla (RVM) to the activation of brainstem inhibitory output neurons and analgesia produced by systemic morphine administration. The NMDA receptor antagonist D-2-amino-5-phosophonopentanoic acid (AP5), the non-NMDA receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione disodium (CNQX) or saline was infused into the RVM of lightly anesthetized rats while recording the activity of identified pain modulating neurons: 'off-cells', thought to inhibit nociceptive transmission, and 'on-cells', thought to facilitate nociception. Nociceptive responsiveness (tail flick latency) was not affected by either antagonist. AP5, but not CNQX, attenuated or blocked activation and disinhibition of off-cells and the antinociception produced by systemically administered morphine. Reflex-related discharge of on-cells was unaffected by AP5, but significantly attenuated by CNQX. The present results ...Continue Reading

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Citations

Oct 1, 2009·Neurotherapeutics : the Journal of the American Society for Experimental NeuroTherapeutics·Kirsty BannisterAnthony H Dickenson
Jan 22, 2003·Peptides·Richard J Bodnar, Maria M Hadjimarkou
May 30, 2002·Progress in Neurobiology·Mark J Millan
Dec 18, 2009·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Akiko Okada-OgawaIan D Meng
Mar 6, 2007·Neuropharmacology·Lindsay B HoughRebecca Stadel
Jan 17, 2009·Brain Research Reviews·M M HeinricherB M Lumb
Oct 27, 2007·Journal of Neurochemistry·Raf Jan-Filip SchepersToni Shaun Shippenberg
Jun 24, 2010·Neuroscience·M M HeinricherL B Hough
Sep 11, 2007·Cellular Signalling·María Rodríguez-MuñozJavier Garzón
Aug 20, 2005·European Journal of Pharmacology·Andrey A MalyshkinAnton Y Bespalov
Mar 25, 2014·Neuron·Christian BüchelFalk Eippert
Jul 28, 2004·Pain·Miranda J NeubertMary M Heinricher
Jan 16, 2004·The Journal of Pharmacology and Experimental Therapeutics·Thomas F FinneganHui-Lin Pan
Jun 28, 2003·Natural Product Reports·Kenneth W Bentley

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