title: Strontium ranelate analgesia in arthritis models is associated to decreased cytokine release and opioid-dependent mechanisms.
abstract: OBJECTIVE
  We investigated the anti-inflammatory activity of strontium ranelate (SR) in arthritis models.
  
  
  METHODS
  Rats received 1 mg zymosan (Zy) or saline intra-articularly. Other groups were subjected to anterior cruciate ligament transection in the right knee, as an osteoarthritis (OA) model, or a sham procedure. Joint pain was assessed using the articular incapacitation and paw-pressure tests. Cell influx and cytokines were measured in joint exudates.
  
  
  METHODS
  Groups received either SR (30-300 mg/kg per os) or saline.
  
  
  RESULTS
  SR dose-dependently and significantly inhibited joint pain in both Zy and OA models, while not altering cell influx. Naloxone administration significantly reversed SR analgesia. SR significantly reduced levels of Interleukin-1β and tumor necrosis factor-α in Zy arthritis, whereas those of cytokine-induced neutrophil chemoattractant (CINC)-1 were not altered.
  
  
  CONCLUSIONS
  SR provides analgesia in arthritis that is associated to inhibition of the release of inflammatory cytokines into inflamed joints. This effect is abrogated by administration of the opioid antagonist naloxone.
authors.affiliation: Department of Internal Medicine, Faculty of Medicine, Federal University of Ceará, R. Dr. Jose Lourenco, 1930, Fortaleza, Ceará, 60115-281, Brazil.
authors.forename: Rodolfo
authors.initials: R
authors.lastname: de Melo Nunes
authors.affiliation: Department of Internal Medicine, Faculty of Medicine, Federal University of Ceará, R. Dr. Jose Lourenco, 1930, Fortaleza, Ceará, 60115-281, Brazil.
authors.forename: Morgana Ramos
authors.initials: MR
authors.lastname: Martins
authors.affiliation: Department of Internal Medicine, Faculty of Medicine, Federal University of Ceará, R. Dr. Jose Lourenco, 1930, Fortaleza, Ceará, 60115-281, Brazil.
authors.forename: Francisco Saraiva
authors.initials: FS
authors.lastname: da Silva Junior
authors.affiliation: Department of Internal Medicine, Faculty of Medicine, Federal University of Ceará, R. Dr. Jose Lourenco, 1930, Fortaleza, Ceará, 60115-281, Brazil.
authors.forename: Ana Caroline Rocha
authors.initials: AC
authors.lastname: de Melo Leite
authors.affiliation: Department of Morphology, Faculty of Medicine, Federal University of Ceará, Fortaleza, Ceará, Brazil.
authors.forename: Virgínia Claudia Carneiro
authors.initials: VC
authors.lastname: Girão
authors.affiliation: Department of Pharmacology, School of Medicine of Ribeirão Preto, University of São Paulo, Ribeirão Preto, São Paulo, Brazil.
authors.forename: Fernando
authors.initials: F
authors.lastname: de Queiroz Cunha
authors.affiliation: Department of Internal Medicine, Faculty of Medicine, Federal University of Ceará, R. Dr. Jose Lourenco, 1930, Fortaleza, Ceará, 60115-281, Brazil.
authors.forename: Aryana Lushese Lima Feitosa
authors.initials: AL
authors.lastname: Marinho
authors.affiliation: Department of Internal Medicine, Faculty of Medicine, Federal University of Ceará, R. Dr. Jose Lourenco, 1930, Fortaleza, Ceará, 60115-281, Brazil.
authors.forename: Ana Carolina Matias Dinelly
authors.initials: AC
authors.lastname: Pinto
authors.affiliation: Department of Internal Medicine, Faculty of Medicine, Federal University of Ceará, R. Dr. Jose Lourenco, 1930, Fortaleza, Ceará, 60115-281, Brazil. arocha@ufc.br.
authors.forename: Francisco Airton Castro
authors.initials: FA
authors.lastname: Rocha
mesh_terms: D018712:Analgesics, Non-Narcotic / Q000627:therapeutic use*; D000818:Animals; D018771:Arthralgia / Q000188:drug therapy; D054360:Chemokine CXCL1 / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D007270:Injections, Intra-Articular; D053583:Interleukin-1beta / Q000378:metabolism; D007596:Joints / Q000473:pathology; D009270:Naloxone / Q000627:therapeutic use; D009292:Narcotic Antagonists / Q000494:pharmacology; D010003:Osteoarthritis / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D010147:Pain Measurement; D051381:Rats; D017208:Rats, Wistar; D011957:Receptors, Opioid / Q000187:drug effects*; D013876:Thiophenes / Q000627:therapeutic use*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D018712:Analgesics, Non-Narcotic; D054360:Chemokine CXCL1; C513297:Cxcl1 protein, rat; D016207:Cytokines; D053583:Interleukin-1beta; D009292:Narcotic Antagonists; D011957:Receptors, Opioid; D013876:Thiophenes; D014409:Tumor Necrosis Factor-alpha; C081587:strontium ranelate; D009270:Naloxone
keywords: Arthritis; Cytokines; Pain; Strontium ranelate; Zymosan