Increase in NADPH-Diaphorase-Positive and Neuronal NO Synthase Immunoreactive Neurons in the Rat Spinal Trigeminal Nucleus Following Infusion of a NO Donor—Evidence for a Feed-Forward Process in NO Production Involved in Trigeminal Nociception

Nitric oxide (NO) donors, which cause delayed headaches in migraineurs, have been shown to activate central trigeminal neurons with meningeal afferent input in animal experiments. Previous reports indicate that this response may be due to up-regulation of NO-producing cells in the trigeminal brainst...

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Veröffentlicht in:Cephalalgia 2009-05, Vol.29 (5), p.566-579
Hauptverfasser: Schlechtweg, PM, Röder, J, Fischer, MJM, Neuhuber, W, Messlinger, K
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Röder, J
Fischer, MJM
Neuhuber, W
Messlinger, K
description Nitric oxide (NO) donors, which cause delayed headaches in migraineurs, have been shown to activate central trigeminal neurons with meningeal afferent input in animal experiments. Previous reports indicate that this response may be due to up-regulation of NO-producing cells in the trigeminal brainstem. To investigate this phenomenon further, we determined nitric oxide synthase (NOS)-containing neurons in the rat spinal trigeminal nucleus (STN), the projection site of nociceptive trigeminal afferents, following infusion of the NO donor sodium nitroprusside (SNP). Barbiturate anaesthetized rats were infused intravenously with SNP (50 μg/kg) or vehicle for 20 min or 2 h, and after periods of 3–8 h fixed by perfusion. Cryostat sections of the medulla oblongata containing the caudal STN were histochemically processed for detection of nicotineamide adenine dinucleotide phosphate (NADPH)-diaphorase or immunohistochemically stained for NOS isoforms and examined by light and fluorescence microscopy. The number of neurons positive for these markers was determined. Various forms of neurons positive for NADPH-diaphorase or immunoreactive to neuronal NOS (nNOS) were found in superficial and deep laminae of the STN caudalis and around the central canal. Neurons were not immunopositive for endothelial (eNOS) or inducible (iNOS) NOS isoforms. The number of NADPH-diaphorase-positive neurons increased time dependently after SNP infusion by a factor of more than two. Likewise, the number of nNOS-immunopositive neurons was increased after SNP compared with vehicle infusion. Around the central canal the number of NADPH-diaphorase-positive neurons was slightly increased and the number of nNOS+ neurons not changed after SNP treatment. NO donors increase the number of neurons that produce NO in the STN, possibly by induction of nNOS expression. Increased NO production may facilitate neurotransmitter release and promote nociceptive transmission in the STN. This mechanism may explain the delayed increase in neuronal activity and headache after infusion of NO donors.
doi_str_mv 10.1111/j.1468-2982.2008.01791.x
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Röder, J ; Fischer, MJM ; Neuhuber, W ; Messlinger, K</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4451-9308c5e8431ae08f516fe4a79a5efb8a56cfe2cd38ae50e929374835462c1d543</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2009</creationdate><topic>Animals</topic><topic>headache</topic><topic>immunofluorescence</topic><topic>Immunohistochemistry</topic><topic>Male</topic><topic>Microscopy, Fluorescence</topic><topic>NADPH Dehydrogenase - biosynthesis</topic><topic>Neurons - drug effects</topic><topic>Neurons - metabolism</topic><topic>Nitric oxide</topic><topic>Nitric Oxide - metabolism</topic><topic>Nitric Oxide Donors - pharmacology</topic><topic>Nitric Oxide Synthase Type I - biosynthesis</topic><topic>Nitroprusside - pharmacology</topic><topic>Pain - metabolism</topic><topic>Pain - physiopathology</topic><topic>Rats</topic><topic>Rats, Wistar</topic><topic>sodium nitroprusside</topic><topic>trigeminal brainstem</topic><topic>Trigeminal Nucleus, Spinal - drug effects</topic><topic>Trigeminal Nucleus, Spinal - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Schlechtweg, PM</creatorcontrib><creatorcontrib>Röder, J</creatorcontrib><creatorcontrib>Fischer, MJM</creatorcontrib><creatorcontrib>Neuhuber, W</creatorcontrib><creatorcontrib>Messlinger, K</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Neurosciences Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Cephalalgia</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext_linktorsrc</fulltext></delivery><addata><au>Schlechtweg, PM</au><au>Röder, J</au><au>Fischer, MJM</au><au>Neuhuber, W</au><au>Messlinger, K</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Increase in NADPH-Diaphorase-Positive and Neuronal NO Synthase Immunoreactive Neurons in the Rat Spinal Trigeminal Nucleus Following Infusion of a NO Donor—Evidence for a Feed-Forward Process in NO Production Involved in Trigeminal Nociception</atitle><jtitle>Cephalalgia</jtitle><addtitle>Cephalalgia</addtitle><date>2009-05</date><risdate>2009</risdate><volume>29</volume><issue>5</issue><spage>566</spage><epage>579</epage><pages>566-579</pages><issn>0333-1024</issn><eissn>1468-2982</eissn><abstract>Nitric oxide (NO) donors, which cause delayed headaches in migraineurs, have been shown to activate central trigeminal neurons with meningeal afferent input in animal experiments. Previous reports indicate that this response may be due to up-regulation of NO-producing cells in the trigeminal brainstem. To investigate this phenomenon further, we determined nitric oxide synthase (NOS)-containing neurons in the rat spinal trigeminal nucleus (STN), the projection site of nociceptive trigeminal afferents, following infusion of the NO donor sodium nitroprusside (SNP). Barbiturate anaesthetized rats were infused intravenously with SNP (50 μg/kg) or vehicle for 20 min or 2 h, and after periods of 3–8 h fixed by perfusion. Cryostat sections of the medulla oblongata containing the caudal STN were histochemically processed for detection of nicotineamide adenine dinucleotide phosphate (NADPH)-diaphorase or immunohistochemically stained for NOS isoforms and examined by light and fluorescence microscopy. The number of neurons positive for these markers was determined. Various forms of neurons positive for NADPH-diaphorase or immunoreactive to neuronal NOS (nNOS) were found in superficial and deep laminae of the STN caudalis and around the central canal. Neurons were not immunopositive for endothelial (eNOS) or inducible (iNOS) NOS isoforms. The number of NADPH-diaphorase-positive neurons increased time dependently after SNP infusion by a factor of more than two. Likewise, the number of nNOS-immunopositive neurons was increased after SNP compared with vehicle infusion. Around the central canal the number of NADPH-diaphorase-positive neurons was slightly increased and the number of nNOS+ neurons not changed after SNP treatment. NO donors increase the number of neurons that produce NO in the STN, possibly by induction of nNOS expression. Increased NO production may facilitate neurotransmitter release and promote nociceptive transmission in the STN. This mechanism may explain the delayed increase in neuronal activity and headache after infusion of NO donors.</abstract><cop>London, England</cop><pub>SAGE Publications</pub><pmid>19220305</pmid><doi>10.1111/j.1468-2982.2008.01791.x</doi><tpages>14</tpages></addata></record>
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identifier ISSN: 0333-1024
ispartof Cephalalgia, 2009-05, Vol.29 (5), p.566-579
issn 0333-1024
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language eng
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source Sage Journals GOLD Open Access 2024
subjects Animals
headache
immunofluorescence
Immunohistochemistry
Male
Microscopy, Fluorescence
NADPH Dehydrogenase - biosynthesis
Neurons - drug effects
Neurons - metabolism
Nitric oxide
Nitric Oxide - metabolism
Nitric Oxide Donors - pharmacology
Nitric Oxide Synthase Type I - biosynthesis
Nitroprusside - pharmacology
Pain - metabolism
Pain - physiopathology
Rats
Rats, Wistar
sodium nitroprusside
trigeminal brainstem
Trigeminal Nucleus, Spinal - drug effects
Trigeminal Nucleus, Spinal - metabolism
title Increase in NADPH-Diaphorase-Positive and Neuronal NO Synthase Immunoreactive Neurons in the Rat Spinal Trigeminal Nucleus Following Infusion of a NO Donor—Evidence for a Feed-Forward Process in NO Production Involved in Trigeminal Nociception
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