Participation of cyclooxygenases in cutaneous thermal nociception under non-inflamed and inflamed conditions.
OBJECTIVE
Effects of cyclooxygenase inhibitors on noxious thermal stimuli were investigated in non-inflamed and inflamed rats.


METHODS
Male Sprague-Dawley rats were used in this study.


METHODS
Cyclooxygenase inhibitors, indomethacin, mofezolac, NS-398, and JTE-522 were administered orally at a dose of 10 mg/kg 1 h prior to and 4 h after the intravenous injection of lipopolysaccharide (1 mg/kg).


METHODS
The nociceptive response was evaluated from the escape latency of foot withdrawal to the thermal stimuli with a beam of light. Expression ofcyclooxygenase was examined by reverse transcription-polymerase chain reaction.


RESULTS
In normal rat, administration of indomethacin, relatively cyclooxygenase-1-selective inhibitor, mofezolac, or cyclooxygenase-2-selective inhibitors, NS-398 and JTE-522 had no effects on the escape latency against thermal stimuli. Injection of lipopolysaccharide into rat induced the expression of mRNA for cyclooxygenase-2 in the subcutaneous tissue of foot pad. The escape latency at 8 h was significantly shortened by the injection. This hyperalgesia could be reversed by pretreatment of rat with NS-398 or JTE-522, but not with mofezolac.


CONCLUSIONS
Cyclooxygenases may have little participation in peripheral skin thermal nociception in non-inflamed condition, although cyclooxygenase-2 could be responsible for the hyperalgesia during inflammation induced by lipopolysaccharide.
Suzuki
M
M
Department of Molecular Pharmacology, Kitasato University Graduate School of Medical Sciences, Sagamihara, Japan.
Hayash
I
I
Nara
Y
Y
Kumaga
Y
Y
Okamoto
H
H
Hoka
S
S
Majima
M
M
D000818:Animals; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D006358:Hot Temperature; D007249:Inflammation / Q000139:chemically induced / Q000201:enzymology* / Q000473:pathology*; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D009619:Nociceptors / Q000187:drug effects / Q000502:physiology*; D010147:Pain Measurement / Q000187:drug effects; D011451:Prostaglandin-Endoperoxide Synthases / Q000096:biosynthesis / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012867:Skin / Q000294:innervation* / Q000473:pathology*
D016861:Cyclooxygenase Inhibitors; D008070:Lipopolysaccharides; D011451:Prostaglandin-Endoperoxide Synthases