Role of nitric oxide in zymosan induced paw inflammation and thermal hyperalgesia.
OBJECTIVE
To assess the involvement of spinal inducible nitric oxide synthase (iNOS) in inflammation and nociception.


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.
Gühring
H
H
Institut für Experimentelle Pharmakologie and Toxikologie, Universität Erlangen-Nürnberg, Erlangen, Germany.
Tegeder
I
I
Lötsch
J
J
Pahl
A
A
Werner
U
U
Reeh
P W
PW
Rehse
K
K
Brune
K
K
Geisslinger
G
G
D000818:Animals; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005528:Foot; D006358:Hot Temperature; D006930:Hyperalgesia / Q000201:enzymology / Q000209:etiology*; D007249:Inflammation / Q000139:chemically induced* / Q000201:enzymology; D007700:Kinetics; D008239:Lysine / Q000031:analogs & derivatives / Q000493:pharmacokinetics / Q000494:pharmacology; D008297:Male; D009569:Nitric Oxide / Q000502:physiology*; D020030:Nitric Oxide Donors / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000235:genetics; D052247:Nitric Oxide Synthase Type II; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D013116:Spinal Cord / Q000737:chemistry; D013558:Sydnones / Q000494:pharmacology; D015054:Zymosan / Q000008:administration & dosage*
C092610:3-methylsydnone-5-nitrosimine; D004791:Enzyme Inhibitors; C090663:N(6)-(1-iminoethyl)lysine; D020030:Nitric Oxide Donors; D012333:RNA, Messenger; D013558:Sydnones; D009569:Nitric Oxide; D015054:Zymosan; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat; D008239:Lysine