title: Possible sources and sites of action of the nitric oxide involved in synaptic plasticity at spinal lamina I projection neurons.
abstract: The synaptic long-term potentiation between primary afferent C-fibers and spinal lamina I projection neurons is a cellular model for hyperalgesia [Ikeda H, Heinke B, Ruscheweyh R, Sandkühler J (2003) Synaptic plasticity in spinal lamina I projection neurons that mediate hyperalgesia. Science 299:1237-1240]. In lamina I neurons with a projection to the periaqueductal gray, this long-term potentiation is dependent on nitric oxide. In the present study, we used immunohistochemistry to detect possible sources and sites of action of the nitric oxide necessary for the long-term potentiation at lamina I spino-periaqueductal gray neurons in rats. None of the three isoforms of the nitric oxide synthase was expressed in a significant number of lamina I spino-periaqueductal gray neurons or primary afferent C-fibers (as evaluated by staining of their cell bodies in the dorsal root ganglia). However, endothelial and inducible nitric oxide synthase were found throughout the spinal cord vasculature and neuronal nitric oxide synthase was present in a number of neurons in laminae II and III. The nitric oxide target soluble guanylyl cyclase was detected in most lamina I spino-periaqueductal gray neurons and in approximately 12% of the dorsal root ganglion neurons, all of them nociceptive as evaluated by coexpression of substance P. Synthesis of cyclic 3',5'-guanosine monophosphate upon stimulation by a nitric oxide donor confirmed the presence of active guanylyl cyclase in at least a portion of the spino-periaqueductal gray neuronal cell bodies. We therefore propose that nitric oxide generated in neighboring neurons or blood vessels acts on the spino-periaqueductal gray neuron and/or the primary afferent C-fiber to enable long-term potentiation. Lamina I spino-parabrachial neurons were stained for comparison and yielded similar results.
authors.affiliation: Department of Neurophysiology, Center for Brain Research, Medical University of Vienna, Spitalgasse 4, A-1090 Vienna, Austria.
authors.forename: R
authors.initials: R
authors.lastname: Ruscheweyh
authors.affiliation: Department of Neurophysiology, Center for Brain Research, Medical University of Vienna, Spitalgasse 4, A-1090 Vienna, Austria; Neuroanatomy and Interdisciplinary Center for Neurosciences, University of Heidelberg, Im Neuenheimer Feld 307, D-69120 Heidelberg, Germany.
authors.forename: A
authors.initials: A
authors.lastname: Goralczyk
authors.affiliation: Department of Neurophysiology, Center for Brain Research, Medical University of Vienna, Spitalgasse 4, A-1090 Vienna, Austria.
authors.forename: G
authors.initials: G
authors.lastname: Wunderbaldinger
authors.affiliation: Neuroanatomy and Interdisciplinary Center for Neurosciences, University of Heidelberg, Im Neuenheimer Feld 307, D-69120 Heidelberg, Germany.
authors.forename: A
authors.initials: A
authors.lastname: Schober
authors.affiliation: Department of Neurophysiology, Center for Brain Research, Medical University of Vienna, Spitalgasse 4, A-1090 Vienna, Austria. Electronic address: juergen.sandkuehler@meduniwien.ac.at.
authors.forename: J
authors.initials: J
authors.lastname: Sandkühler
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D002452:Cell Count; D048429:Cell Size; D007150:Immunohistochemistry / Q000379:methods; D009252:NADPH Dehydrogenase / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009434:Neural Pathways / Q000033:anatomy & histology / Q000502:physiology; D009473:Neuronal Plasticity / Q000187:drug effects*; D009474:Neurons / Q000145:classification / Q000187:drug effects* / Q000378:metabolism; D009569:Nitric Oxide / Q000494:pharmacology*; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D010487:Periaqueductal Gray / Q000033:anatomy & histology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013116:Spinal Cord / Q000166:cytology*; D013569:Synapses / Q000187:drug effects*
chemical_list: D009419:Nerve Tissue Proteins; D009569:Nitric Oxide; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; D009252:NADPH Dehydrogenase