title: 3-[4-(3-Trifluoromethyl-phenyl)-piperazin-1-yl]-dihydrofuran-2-one and pregabalin attenuate tactile allodynia in the mouse model of chronic constriction injury.
abstract: OBJECTIVE
  There is a strong medical demand to search for novel, more efficacious and safer than available, analgesics for the treatment of neuropathic pain. This study investigated antinociceptive activity of intraperitoneally administered 3-[4-(3-trifluoromethyl-phenyl)-piperazin-1-yl]-dihydrofuran-2-one (LPP1) and pregabalin in the chronic constriction injury (CCI) model of neuropathic pain in mice and evaluated these drugs' influence on motor coordination. In addition, microscopic examinations of the sciatic nerve were performed to assess, if a surgical method or drug treatment caused changes in the structure of this nerve. Moreover, the alterations of nerve growth factor (NGF) content after drug treatment were assessed.
  
  
  METHODS
  Antiallodynic and antihyperalgesic activities of LPP1 and pregabalin were assessed in the von Frey and hot plate tests. Motor-impairing properties were evaluated in the rotarod test. Microscopic examinations of the sciatic nerve were performed using electron microscope. In immunohistochemical assays the content of NGF in the sciatic nerve after single or repeated administration of test drugs was assessed.
  
  
  RESULTS
  Microscopic examinations of the sciatic nerve revealed ultrastructural changes in nerve fibers indicating for neurodegenerative processes induced by CCI. Seven days after CCI surgery LPP1 and pregabalin reduced tactile allodynia in von Frey test (ED50 values were 1.5 and 15.4 mg/kg, respectively). None of the test drugs at dose range 0.5-100 mg/kg induced motor deficits in the rotarod test. In immunohistochemical assays repeated doses of pregabalin and LPP1 elevated NGF content.
  
  
  CONCLUSIONS
  LPP1 has antiallodynic properties and is an interesting lead structure in the search for novel analgesics used in neuropathic pain.
authors.affiliation: a Department of Pharmacodynamics , Chair of Pharmacodynamics, Medical College, Jagiellonian University , Cracow , Poland .
authors.forename: Kinga
authors.initials: K
authors.lastname: Sałat
authors.affiliation: a Department of Pharmacodynamics , Chair of Pharmacodynamics, Medical College, Jagiellonian University , Cracow , Poland .
authors.forename: Jadwiga
authors.initials: J
authors.lastname: Witalis
authors.affiliation: b Department of Pharmacobiology , Medical College, Jagiellonian University , Cracow , Poland .
authors.forename: Monika
authors.initials: M
authors.lastname: Zadrożna
authors.affiliation: c Department of Neuroanatomy , Institute of Zoology, Jagiellonian University , Cracow , Poland .
authors.forename: Zbigniew
authors.initials: Z
authors.lastname: Sołtys
authors.affiliation: b Department of Pharmacobiology , Medical College, Jagiellonian University , Cracow , Poland .
authors.forename: Barbara
authors.initials: B
authors.lastname: Nowak
authors.affiliation: a Department of Pharmacodynamics , Chair of Pharmacodynamics, Medical College, Jagiellonian University , Cracow , Poland .
authors.forename: Barbara
authors.initials: B
authors.lastname: Filipek
authors.affiliation: d Department of Organic Chemistry , Chair of Organic Chemistry, Medical College, Jagiellonian University , Cracow , Poland , and.
authors.forename: Krzysztof
authors.initials: K
authors.lastname: Więckowski
authors.affiliation: e Department of Physicochemical Drug Analysis , Chair of Pharmaceutical Chemistry, Medical College, Jagiellonian University , Cracow , Poland.
authors.forename: Barbara
authors.initials: B
authors.lastname: Malawska
mesh_terms: D015107:4-Butyrolactone / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000700:Analgesics / Q000627:therapeutic use*; D000818:Animals; D003251:Constriction, Pathologic / Q000150:complications*; D004305:Dose-Response Relationship, Drug; D006358:Hot Temperature; D006930:Hyperalgesia / Q000188:drug therapy* / Q000209:etiology; D008297:Male; D051379:Mice; D020932:Nerve Growth Factor / Q000378:metabolism; D009437:Neuralgia / Q000188:drug therapy; D010147:Pain Measurement; D010812:Physical Stimulation; D010879:Piperazines / Q000627:therapeutic use*; D004856:Postural Balance / Q000187:drug effects; D000069583:Pregabalin / Q000627:therapeutic use*; D012584:Sciatic Nerve / Q000187:drug effects / Q000378:metabolism / Q000473:pathology
chemical_list: C547282:3-(4-(3-trifluoromethylphenyl)piperazin-1-yl)dihydrofuran-2-one; D000700:Analgesics; D010879:Piperazines; D000069583:Pregabalin; D020932:Nerve Growth Factor; D015107:4-Butyrolactone
keywords: Chronic constriction injury of the sciatic nerve; dihydrofuran-2-one; mice; nerve growth factor; pregabalin