title: Endothelial nitric oxide synthase in dorsal root ganglia during chronic inflammatory nociception.
abstract: Nitric oxide (NO) is a gaseous molecule implicated both in vascular tone and nociceptive transmission. The capillary blood supply to the dorsal root ganglia (DRG) is unique because it is highly permeable to several low and high molecular-weight compounds. This anatomical situation leads to a potential role of endothelial nitric oxide synthase (eNOS) in inflammatory nociception, which is not well established. Therefore, we examined the role of eNOS in DRG in a murine chronic inflammatory pain model induced by complete Freund's adjuvant using L-N(5)-(1-iminoethyl)ornithine (L-NIO), a potent inhibitor of eNOS activity. Pain state was examined using a behavioral test. The expression of eNOS, platelet endothelial cell adhesion molecule-1 (CD31) and vascular endothelial growth factor (VEGF) was examined by immunofluorescence. In control animals, CD31 was detected in vessels; VEGF was localized both in vessels and neurons while a weak eNOS immunopositivity was detected in both vessels and in neurons. Under inflammatory pain conditions, eNOS, CD31 and VEGF immunopositivity increased. Administration of L-NIO significantly attenuated thermal hyperalgesia by 24 h and decreased eNOS activity and CD31 immunopositivity by 7 days. VEGF was unaffected. Our results show that eNOS plays a nociceptive role in the early phases of inflammation while in the later phases it may be involved in neurotrophic support.
authors.affiliation: Department of Biomedical Sciences and Biotechnologies, Division of Human Anatomy, University of Brescia, Brescia, Italy.
authors.forename: Elisa
authors.initials: E
authors.lastname: Borsani
authors.forename: Sara
authors.initials: S
authors.lastname: Giovannozzi
authors.forename: Marco Angelo
authors.initials: MA
authors.lastname: Cocchi
authors.forename: Ramon
authors.initials: R
authors.lastname: Boninsegna
authors.forename: Rita
authors.initials: R
authors.lastname: Rezzani
authors.forename: Luigi F
authors.initials: LF
authors.lastname: Rodella
mesh_terms: D000818:Animals; D005727:Ganglia, Spinal / Q000201:enzymology*; D006801:Humans; D007249:Inflammation / Q000201:enzymology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism*; D059225:Nociception / Q000502:physiology*; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: D019408:Platelet Endothelial Cell Adhesion Molecule-1; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D052250:Nitric Oxide Synthase Type III