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Role of nitric oxide in zymosan induced paw inflammation and thermal hyperalgesia.

AbstractOBJECTIVE:
To assess the involvement of spinal inducible nitric oxide synthase (iNOS) in inflammation and nociception.
MATERIALS AND METHODS:
The time course of iNOS mRNA expression in rat spinal cord and inflamed paw was assessed by means of quantitative real time RT-PCR. In addition, the effects of the iNOS inhibitor L-NIL on inflammatory paw edema and thermal hyperalgesia were studied in comparison to those of the NO-donor RE-2047. L-NIL (3, 9, 27 and 81 mg/kg) and RE-2047 (3, 9 and 27 mg/kg) or vehicle were administered orally 15 min prior to the intraplantar injection of 0.625 mg zymosan.
RESULTS:
Following zymosan injection, mRNA expression of iNOS increased in the inflamed paw and spinal cord with a maximum at 2.5 and 4 h, respectively. In the spinal cord iNOS mRNA started to decline at 10 h whereas it remained at maximum in the inflamed paw up to the end of the observation period of 24 h. As expected, RE-2047 had significant pronociceptive and proinflammatory effects. L-NIL significantly reduced paw inflammation at 27 and 81 mg/kg but failed to reduce hyperalgesia at the doses tested.
CONCLUSIONS:
The results show that iNOS is upregulated in the inflamed tissue and spinal cord with a similar time course. The effects obtained with L-NIL suggest that iNOS differently contributes to the inflammatory and nociceptive response induced by zymosan.
AuthorsH Gühring, I Tegeder, J Lötsch, A Pahl, U Werner, P W Reeh, K Rehse, K Brune, G Geisslinger
JournalInflammation research : official journal of the European Histamine Research Society ... [et al.] (Inflamm Res) Vol. 50 Issue 2 Pg. 83-8 (Feb 2001) ISSN: 1023-3830 [Print] Switzerland
PMID11289658 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • 3-methylsydnone-5-nitrosimine
  • Enzyme Inhibitors
  • N(6)-(1-iminoethyl)lysine
  • Nitric Oxide Donors
  • RNA, Messenger
  • Sydnones
  • Nitric Oxide
  • Zymosan
  • Nitric Oxide Synthase
  • Nitric Oxide Synthase Type II
  • Nos2 protein, rat
  • Lysine
Topics
  • Animals
  • Enzyme Inhibitors (pharmacology)
  • Foot
  • Hot Temperature
  • Hyperalgesia (enzymology, etiology)
  • Inflammation (chemically induced, enzymology)
  • Kinetics
  • Lysine (analogs & derivatives, pharmacokinetics, pharmacology)
  • Male
  • Nitric Oxide (physiology)
  • Nitric Oxide Donors (pharmacology)
  • Nitric Oxide Synthase (antagonists & inhibitors, genetics)
  • Nitric Oxide Synthase Type II
  • RNA, Messenger (analysis)
  • Rats
  • Rats, Sprague-Dawley
  • Spinal Cord (chemistry)
  • Sydnones (pharmacology)
  • Zymosan (administration & dosage)

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