title: The spinal cord expression of neuronal and inducible nitric oxide synthases and their contribution in the maintenance of neuropathic pain in mice.
abstract: BACKGROUND
  Nitric oxide generated by neuronal (NOS1), inducible (NOS2) or endothelial (NOS3) nitric oxide synthases contributes to pain processing, but the exact role of NOS1 and NOS2 in the maintenance of chronic peripheral neuropathic pain as well as the possible compensatory changes in their expression in the spinal cord of wild type (WT) and NOS knockout (KO) mice at 21 days after total sciatic nerve ligation remains unknown.
  
  
  RESULTS
  The mechanical and thermal allodynia as well as thermal hyperalgesia induced by sciatic nerve injury was evaluated in WT, NOS1-KO and NOS2-KO mice from 1 to 21 days after surgery. The mRNA and protein levels of NOS1, NOS2 and NOS3 in the spinal cord of WT and KO mice, at 21 days after surgery, were also assessed. Sciatic nerve injury led to a neuropathic syndrome in WT mice, in contrast to the abolished mechanical allodynia and thermal hyperalgesia as well as the decreased or suppressed thermal allodynia observed in NOS1-KO and NOS2-KO animals, respectively. Sciatic nerve injury also increases the spinal cord expression of NOS1 and NOS2 isoforms, but not of NOS3, in WT and NOS1-KO mice respectively. Moreover, the presence of NOS2 is required to increase the spinal cord expression of NOS1 whereas an increased NOS1 expression might avoid the up-regulation of NOS2 in the spinal cord of nerve injured WT mice.
  
  
  CONCLUSIONS
  These data suggest that the increased spinal cord expression of NOS1, regulated by NOS2, might be responsible for the maintenance of chronic peripheral neuropathic pain in mice and propose these enzymes as interesting therapeutic targets for their treatment.
authors.affiliation: Grup de Neurofarmacologia Molecular, Institut de Recerca de l'Hospital de la Sta Creu i Sant Pau & Institut de Neurociències, Universitat Autònoma de Barcelona, Barcelona, Spain.
authors.forename: Arnau
authors.initials: A
authors.lastname: Hervera
authors.forename: Roger
authors.initials: R
authors.lastname: Negrete
authors.forename: Sergi
authors.initials: S
authors.lastname: Leánez
authors.forename: Jesús M
authors.initials: JM
authors.lastname: Martín-Campos
authors.forename: Olga
authors.initials: O
authors.lastname: Pol
mesh_terms: D000818:Animals; D015971:Gene Expression Regulation, Enzymologic; D005838:Genotype; D006358:Hot Temperature; D006930:Hyperalgesia / Q000235:genetics; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D052248:Nitric Oxide Synthase Type I / Q000096:biosynthesis*; D052247:Nitric Oxide Synthase Type II / Q000096:biosynthesis*; D052250:Nitric Oxide Synthase Type III / Q000096:biosynthesis*; D010146:Pain / Q000503:physiopathology*; D013116:Spinal Cord / Q000201:enzymology / Q000378:metabolism*
chemical_list: D052248:Nitric Oxide Synthase Type I; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; C496317:Nos2 protein, mouse; C496315:Nos3 protein, mouse