Autophagy and cathepsin L are involved in the antinociceptive effect of DMBC in a mouse acetic acid-writhing model

• Published in: Acta pharmacologica Sinica Vol. 34; no. 8; pp. 1007 - 1012
• Main Authors: Gu, Wei-wei, Ao, Gui-zhen, Zhu, Yong-ming, Sun, Shi-chang, Zhou, Qiang, Fan, Jia-hong, Nobuhiko, Katunuma, Ishidoh, Kazumi, Zhang, Hui-ling, Gao, Xiu-mei
• Format: Journal Article
• Language: English
• Published: United States Nature Publishing Group 01.08.2013
• Subjects: Acetic Acid - toxicity; Analgesics - administration & dosage; Analgesics - chemistry; Animals; Autophagy - drug effects; Autophagy - physiology; Benzylidene Compounds - administration & dosage; Benzylidene Compounds - chemistry; Cathepsin L - antagonists & inhibitors; Cathepsin L - metabolism; Cyclopentanes - administration & dosage; Cyclopentanes - chemistry; Disease Models, Animal; Epoxy Compounds - administration & dosage; Female; Injections, Intraventricular; Male; Mice; Mice, Inbred ICR; Original; Pain - chemically induced; Pain - drug therapy; Pain - metabolism; Pain Measurement - drug effects; Pain Measurement - methods; Pyridines - administration & dosage; Signal Transduction - physiology; 伤害作用; 体模型; 小鼠; 组织蛋白酶; 自噬; 醋酸; 镇痛作用; 集中管理
• ISSN: 1671-4083; 1745-7254
• DOI: 10.1038/aps.2013.30

Aim： 2-（3＇,5＇-Dimethoxybenzylidene） cyclopentanone （DMBC） is a novel synthetic compound with antinociceptive activities. The aim of this study was to investigate the roles of the autophagic-lysosomal pathway in the antinociceptive effect of DMBC in a mouse acetic acid-writhing model. Methods： Mouse acetic acid-writhing test and hotplate test were used to assess the antinociceptive effects of DMBC, 3-MA （autophagy inhibitor） and Clik148 （cathepsin L inhibitor）. The drugs were administered peripherally （ip） or centrally （icy）. Results： Peripheral administration of 3-MA （7.5-30 mg/kg） or Clik148 （10-80 mg/kg） produced potent antinociceptive effect in acetic acid-writhing test. Central administration of 3-MA or Clik148 （12.5-50 nmol/L） produced comparable antinociceptive effect in acetic acid-writhing test. Peripheral administration of DMBC （25-50 mg/kg） produced potent antinociceptive effects in both acetic acid- writhing and hotplate tests. Furthermore, the antinociceptive effect produced by peripheral administration of DMBC （50 mg/kg） in acetic acid-writhing test was antagonized by low doses of 3-MA （3.75 mg/kg） or Clik148 （20 mg/kg） peripherally administered, but was not affected by 3-MA or Clik148 （25 nmol/L） centrally administered. Conclusion： Activation of central autophagy and cathepsin L is involved in nociception in mice, whereas peripheral autophagy and cathepsin L contributes, at least in part, to the antinociceptive effect of DMBC in mice.