Strontium ranelate analgesia in arthritis models is associated to decreased cytokine release and opioid-dependent mechanisms

Inflamm Res. 2015 Oct;64(10):781-7. doi: 10.1007/s00011-015-0860-7. Epub 2015 Aug 6.

Abstract

Objective: We investigated the anti-inflammatory activity of strontium ranelate (SR) in arthritis models.

Materials and 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.

Treatment: 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.

Keywords: Arthritis; Cytokines; Pain; Strontium ranelate; Zymosan.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Analgesics, Non-Narcotic / therapeutic use*
  • Animals
  • Arthralgia / drug therapy
  • Chemokine CXCL1 / metabolism
  • Cytokines / metabolism*
  • Dose-Response Relationship, Drug
  • Injections, Intra-Articular
  • Interleukin-1beta / metabolism
  • Joints / pathology
  • Naloxone / therapeutic use
  • Narcotic Antagonists / pharmacology
  • Osteoarthritis / drug therapy*
  • Osteoarthritis / metabolism*
  • Osteoarthritis / pathology
  • Pain Measurement
  • Rats
  • Rats, Wistar
  • Receptors, Opioid / drug effects*
  • Thiophenes / therapeutic use*
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • Analgesics, Non-Narcotic
  • Chemokine CXCL1
  • Cxcl1 protein, rat
  • Cytokines
  • Interleukin-1beta
  • Narcotic Antagonists
  • Receptors, Opioid
  • Thiophenes
  • Tumor Necrosis Factor-alpha
  • strontium ranelate
  • Naloxone