Abstract | BACKGROUND: METHODS: Monoarthritis was induced by an injection of complete Freund's adjuvant (CFA) intracapsularly into the tibiotarsal joint of the rats. Withdrawal latencies to thermal stimulation on the hind paw, withdrawal thresholds to mechanical stimulation, paw volume, and ankle diameter were measured 24 h and 4 weeks after the CFA injection. A novel selective EP(4) receptor agonist, ONO-AE1-329 (10, 25, or 50 microg) or saline was administered intracapsularly into the joint. RESULTS: Withdrawal latencies and withdrawal thresholds were significantly (P < 0.05) shortened and decreased, respectively, on the arthritic side but not on the contralateral side 24 h and 4 weeks after the CFA injection. In addition, significant (P < 0.05) increases in paw volume and ankle diameter on the arthritic side were observed. Intracapsularly administered ONO-AE1-329 showed significant (P < 0.05) inhibition of thermal and mechanical hyperalgesia and significant (P < 0.05) decrease in paw volume and ankle diameter in a dose-dependent manner at 24 h and 4 weeks after CFA. CONCLUSION: Intracapsular administration of EP(4) receptor agonist effectively inhibited mechanical and thermal hyperalgesia and inflammatory reactions in acute and chronic monoarthritis. An EP(4) agonist would be a potential strategy for inflammatory pain in arthritis.
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Authors | Keiichi Omote, Tomoyuki Kawamata, Yoshito Nakayama, Hiroki Yamamoto, Mikito Kawamata, Akiyoshi Namiki |
Journal | Anesthesiology
(Anesthesiology)
Vol. 97
Issue 1
Pg. 170-6
(Jul 2002)
ISSN: 0003-3022 [Print] United States |
PMID | 12131119
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Analgesics, Non-Narcotic
- Cytokines
- Methyl Ethers
- ONO-AE1-329
- Ptger4 protein, rat
- Receptors, Prostaglandin E
- Receptors, Prostaglandin E, EP4 Subtype
- Tumor Necrosis Factor-alpha
- Freund's Adjuvant
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Topics |
- Analgesics, Non-Narcotic
(therapeutic use)
- Animals
- Arthritis, Experimental
(drug therapy)
- Cytokines
(biosynthesis)
- Freund's Adjuvant
- Hyperalgesia
(drug therapy)
- Male
- Methyl Ethers
(therapeutic use)
- Rats
- Rats, Sprague-Dawley
- Reaction Time
(drug effects)
- Receptors, Prostaglandin E
(agonists, physiology)
- Receptors, Prostaglandin E, EP4 Subtype
- Tumor Necrosis Factor-alpha
(pharmacology)
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