The kappa opioid receptor agonist SA14867 has antinociceptive and weak sedative effects in models of acute and chronic pain
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- 作者：Yaeko ; Tsukahara-Ohsumi
- 关键词：SA14867 ; Kappa opioid receptor agonist ; Specific alternation of rhythm in environmental temperature (SART)-stressed model ; Arthritis-induced hyperalgesia model ; Sciatic nerve ligation model
- 刊名：European Journal of Pharmacology
- 出版年：2011
- 出版时间：5 December 2011
- 年：2011
- 卷：671
- 期：1-3
- 页码：53-60
- 全文大小：2811 K
文摘
We examined the analgesic effect of the selective kappa opioid receptor agonist SA14867 and the balance of its antinociceptive and sedative effects. The EDub xmlns="""">50 ub> values of SA14867 after oral administration for acetic acid-induced writhing, first and second phases of the formalin test, and rotarod test in mice were 6.1, 9.3, 2.7, and 19.5 mg/kg, respectively. These values were smaller than those of the conventional kappa receptor agonists asimadoline and U-50488H. However, the balance of the antinociceptive and sedative effects of SA14867 was better than those of the other two drugs. Orally administered SA14867 (0.1? mg/kg) significantly improved the decreased pain threshold in a specific alternation of rhythm in an environmental temperature (SART)-stressed model by prophylactic and therapeutic treatment. Improvement in the decreased pain threshold of SA14867-treated animals was attenuated by the opioid receptor antagonist naloxone. Furthermore, orally administered asimadoline (10?00 mg/kg) improved the decreased pain threshold in a SART-stressed model, but the doses were close to those known to induce sedative effects. In addition, SA14867 (0.1? mg/kg) significantly inhibited the arthritis-induced decrease in the pain threshold. Subcutaneously administered morphine (0.1? mg/kg) improved the decreased pain threshold in a SART-stressed model; on the contrary, morphine did not inhibit the arthritis-induced decrease in the pain threshold. Moreover, orally administered SA14867 (0.1? mg/kg) strongly attenuated mechanical allodynia and thermal hyperalgesia in a sciatic nerve ligation model. These results suggest that SA14867 has analgesic effects on chronic pain and may serve as a new therapeutic agent for pain treatment.