title: Nitric oxide is negatively correlated to pain during acute inflammation.
abstract: BACKGROUND
  The role that nitric oxide (NO) plays in modulating pain in the periphery is unclear. We show here, the results of two independent clinical studies (microdialysis and gene expression studies) and a pilot dose finding study (glyceryl trinitrate study), to study the role of NO in the early phase of acute inflammatory pain following oral surgery. The effect of ketorolac on NO production and nitric oxide synthase (NOS) gene expression was also studied.
  
  
  RESULTS
  Microdialysis samples showed significantly higher levels of NO at the first 100 min compared to the last 80 minutes in the placebo treated group. In the ketorolac group, on the other hand, NO levels gradually decreased over the first 60 min but were similar to placebo over the later 100-180 min, with no significant change in NO level over time. The levels of NO were negatively correlated to pain intensity scores. Local infusion of the NO donor glyceryl trinitrate at the site of surgery, showed a small analgesic effect that did not reach statistical significance in the sample size used. While the gene expression of iNOS and eNOS were not up-regulated, 3 hours after surgery, nNOS was downregulated in both treatment groups and eNOS gene expression was significantly lower in the ketorolac group compared to the placebo group. Further, there was a positive correlation between the change in gene expression of nNOS and eNOS in the placebo group but not in the ketorolac group.
  
  
  CONCLUSIONS
  We suggest that at this early stage of inflammatory pain in man, NO is analgesic in the periphery. Further, ketorolac down-regulates eNOS gene expression.
authors.affiliation: NINR/NIH, Bethesda, MD 20892, USA.
authors.forename: May
authors.initials: M
authors.lastname: Hamza
authors.forename: Xiao-Min
authors.initials: XM
authors.lastname: Wang
authors.forename: Tongtong
authors.initials: T
authors.lastname: Wu
authors.forename: Jaime S
authors.initials: JS
authors.lastname: Brahim
authors.forename: Janet S
authors.initials: JS
authors.lastname: Rowan
authors.forename: Raymond A
authors.initials: RA
authors.lastname: Dionne
mesh_terms: D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D005260:Female; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D006801:Humans; D007249:Inflammation / Q000150:complications* / Q000188:drug therapy*; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism; D020910:Ketorolac / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D016014:Linear Models; D008297:Male; D017551:Microdialysis; D008954:Models, Biological; D009569:Nitric Oxide / Q000378:metabolism*; D020030:Nitric Oxide Donors / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D019001:Nitric Oxide Synthase / Q000235:genetics / Q000378:metabolism; D005996:Nitroglycerin / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D010146:Pain / Q000150:complications* / Q000188:drug therapy*; D055815:Young Adult
chemical_list: D007527:Isoenzymes; D020030:Nitric Oxide Donors; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D005996:Nitroglycerin; D020910:Ketorolac