Etodolac attenuates mechanical allodynia in a mouse model of neuropathic pain.
Cyclooxygenase (COX) contributes to neuropathic pain after peripheral nerve injury, yet COX inhibitors are generally ineffective against mechanical allodynia and hyperalgesia in neuropathic pain patients and animal models. In the present study, we investigated the effects of etodolac, a selective COX-2 inhibitor, on mechanical allodynia in mice after partial sciatic nerve ligation (PSNL) compared to indomethacin (a nonselective COX inhibitor) or celecoxib (a selective COX-2 inhibitor). PSNL decreased the paw-withdrawal threshold (PWT) as assessed by the von Frey hair test, and etodolac, but not indomethacin or celecoxib, administered daily for two weeks, partially or wholly reversed the decrease. The efficacy of etodolac gradually increased throughout the administration period, and the higher dosages restored preligation PWT values by day 21. The positive control pregabalin also partially or wholly reversed the decrease in PWT, but in contrast to etodolac, it showed no increase in efficacy throughout the administration period. In normal mice, etodolac did not affect the PWT, whereas pregabalin increased it. These findings suggest that the mechanisms of inhibition of mechanical allodynia by etodolac and pregabalin are different and demonstrate that in contrast to other COX inhibitors, etodolac is effective against mechanical allodynia in a mouse neuropathic pain model.
Discovery Research Laboratories, Nippon Shinyaku Co, Ltd, Kisshoin, Kyoto, Japan. n.inoue@po.nippon-shinyaku.co.jp
Naoki
N
Inoue
Sunao
S
Ito
Koyuki
K
Tajima
Masaki
M
Nogawa
Yosuke
Y
Takahashi
Takahiro
T
Sasagawa
Akio
A
Nakamura
Takashi
T
Kyoi
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D002351:Carrageenan; D000068579:Celecoxib; D052246:Cyclooxygenase 2 Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D004487:Edema / Q000139:chemically induced / Q000188:drug therapy / Q000473:pathology; D017308:Etodolac / Q000494:pharmacology*; D007202:Indicators and Reagents; D008026:Ligation; D008297:Male; D051379:Mice; D010146:Pain / Q000188:drug therapy* / Q000209:etiology; D010147:Pain Measurement / Q000187:drug effects; D000069583:Pregabalin; D011720:Pyrazoles / Q000494:pharmacology / Q000627:therapeutic use; D020426:Sciatic Neuropathy / Q000150:complications* / Q000473:pathology; D013449:Sulfonamides / Q000494:pharmacology / Q000627:therapeutic use; D005680:gamma-Aminobutyric Acid / Q000031:analogs & derivatives / Q000494:pharmacology / Q000627:therapeutic use
D000894:Anti-Inflammatory Agents, Non-Steroidal; D052246:Cyclooxygenase 2 Inhibitors; D007202:Indicators and Reagents; D011720:Pyrazoles; D013449:Sulfonamides; D017308:Etodolac; D000069583:Pregabalin; D005680:gamma-Aminobutyric Acid; D002351:Carrageenan; D000068579:Celecoxib