Mathematical analysis of involvement ratio between central and peripheral COX-2 in rat pain models with two types of COX-2 inhibitors with different distribution, celecoxib and CIAA.
The purpose of this study is to clarify involvement ratios between central and peripheral cyclooxygenase (COX)-2 in rat inflammatory pain models, by evaluating celecoxib and [6-chloro-2-(4-chlorobenzoyl)-1H-indol-3-yl]acetic acid (CIAA) on carrageenan-induced mechanical and thermal hyperalgesia. Celecoxib and CIAA exhibited ID(30) values with 1.5 and 7.7 mg/kg on mechanical hyperalgesia, respectively, and ID(25) values with 0.54 and 36 mg/kg on thermal hyperalgesia, respectively. By solving quadratic functional analysis with prostaglandin E(2) (PGE(2)) inhibitory activities, it was calculated that involvement ratios between central and peripheral COX-2 involvement were 0.47 and 0.53 on mechanical hyperalgesia, and 0.97 and 0.03 on thermal hyperalgesia, respectively. These data suggest that central and peripheral COX-2 are equally involved in mechanical hyperalgesia, while central COX-2 is predominantly involved in thermal hyperalgesia.
Okumura
Takako
T
Discovery Biology Research, Nagoya Laboratories, Pfizer Global Research and Development, Pfizer Inc., 5-2 Taketoyo, Aichi, 470-2393, Japan. Takako.Okumura@pfizer.com
Sakakibara
Ayano
A
Murata
Yoko
Y
Kita
Yasuhiro
Y
D000818:Animals; D002351:Carrageenan; D000068579:Celecoxib; D002723:Chlorobenzoates / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*; D051546:Cyclooxygenase 2 / Q000187:drug effects / Q000378:metabolism*; D052246:Cyclooxygenase 2 Inhibitors / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*; D015232:Dinoprostone / Q000378:metabolism; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D006358:Hot Temperature; D006930:Hyperalgesia / Q000188:drug therapy / Q000503:physiopathology; D007210:Indoleacetic Acids / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*; D007249:Inflammation / Q000188:drug therapy / Q000503:physiopathology; D008297:Male; D008954:Models, Biological; D010146:Pain / Q000188:drug therapy / Q000503:physiopathology*; D010147:Pain Measurement; D011720:Pyrazoles / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013449:Sulfonamides / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*; D014018:Tissue Distribution
C479620:(6-chloro-2-(4-chlorobenzoyl)-1H-indol-3-yl)acetic acid; D002723:Chlorobenzoates; D052246:Cyclooxygenase 2 Inhibitors; D007210:Indoleacetic Acids; D011720:Pyrazoles; D013449:Sulfonamides; D002351:Carrageenan; D051546:Cyclooxygenase 2; D000068579:Celecoxib; D015232:Dinoprostone