title: Autophagy and cathepsin L are involved in the antinociceptive effect of DMBC in a mouse acetic acid-writhing model.
abstract: OBJECTIVE
  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 (icv).
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Pharmacology and Laboratory of Cerebrovascular Pharmacology, College of Pharmaceutical Science, Soochow University, Suzhou 215123, China.
authors.forename: Wei-wei
authors.initials: WW
authors.lastname: Gu
authors.forename: Gui-zhen
authors.initials: GZ
authors.lastname: Ao
authors.forename: Yong-ming
authors.initials: YM
authors.lastname: Zhu
authors.forename: Shi-chang
authors.initials: SC
authors.lastname: Sun
authors.forename: Qiang
authors.initials: Q
authors.lastname: Zhou
authors.forename: Jia-hong
authors.initials: JH
authors.lastname: Fan
authors.forename: Katunuma
authors.initials: K
authors.lastname: Nobuhiko
authors.forename: Kazumi
authors.initials: K
authors.lastname: Ishidoh
authors.forename: Hui-ling
authors.initials: HL
authors.lastname: Zhang
authors.forename: Xiu-mei
authors.initials: XM
authors.lastname: Gao
mesh_terms: D019342:Acetic Acid / Q000633:toxicity*; D000700:Analgesics / Q000008:administration & dosage* / Q000737:chemistry; D000818:Animals; D001343:Autophagy / Q000187:drug effects / Q000502:physiology*; D001597:Benzylidene Compounds / Q000008:administration & dosage* / Q000737:chemistry*; D056668:Cathepsin L / Q000037:antagonists & inhibitors / Q000378:metabolism*; D003517:Cyclopentanes / Q000008:administration & dosage* / Q000737:chemistry*; D004195:Disease Models, Animal; D004852:Epoxy Compounds / Q000008:administration & dosage; D005260:Female; D007276:Injections, Intraventricular; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D010146:Pain / Q000139:chemically induced / Q000188:drug therapy / Q000378:metabolism*; D010147:Pain Measurement / Q000187:drug effects / Q000379:methods; D011725:Pyridines / Q000008:administration & dosage; D015398:Signal Transduction / Q000502:physiology
chemical_list: C000589425:2-(3',5'-dimethoxybenzylidene)cyclopentanone; D000700:Analgesics; D001597:Benzylidene Compounds; C402823:CLIK 148; D003517:Cyclopentanes; D004852:Epoxy Compounds; D011725:Pyridines; C007201:cyclopentanone; D056668:Cathepsin L; D019342:Acetic Acid
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