Anti-inflammatory and anti-nociceptive effects of strontium ranelate on the zymosan-induced temporomandibular joint inflammatory hypernociception in rats depend on TNF-α inhibition

Abstract

Strontium ranelate may achieve its antinociceptive effects through the reduction of TNF-α levels in the trigeminal ganglion, but not suppressing IL-1β expression nor inducing the HO-1 pathway.

Prophylactic and Therapeutic Use of Strontium Ranelate Reduces the Progression of Experimental Osteoarthritis

“…SrRan (0.5, 5, and 50 mg/kg/day) also exhibited antinociceptive effects on the temporomandibular joint of rats in a zymosan-induced model of OA by reducing hypernociception, assessed using the Von Frey test. This phenomenon was verified, for the first time, in the present study at doses of 500 mg/kg/day, probably because the magnitude of OA induced in the knee was different from that induced in the temporomandibular joint ( Alves et al, 2017 ). This was also verified at 300 mg/kg/day but not at 30 mg/kg/day in zymosan-induced knee OA ( Nunes et al, 2015 ).…”

“…This result corroborates available data showing a reduction in synovial fluid levels of TNF-α and IL-1β in zymosan-induced OA rats treated with SrRan at a dose of 300 mg/kg/day ( Nunes et al, 2015 ). A decrease in the expression of TNF-α without changes in leukocyte count and IL-1β levels was also observed in another pre-clinical study of periarticular tissue samples, with lower doses of SrRan (up to 50 mg/kg/day) ( Alves et al, 2017 ). These results were not confirmed in a study with rats subjected to oophorectomy and treated with SrRan at doses of 300 and 625 mg/kg/day, with no reduction of TNF-α and MMPs, which are metal-dependent endopeptidases that remodel the extracellular matrix ( Mierzwa et al, 2017 ).…”

“…The benefit of the prophylactic use of SrRan was also verified by analyzing its effects on hyperalgesia induced by increasing the pressure on the rat’s paw, based on the fact that inflammation lowers the threshold of pain reactions. SrRan showed similar effects in other studies; however, these studies treated already established OA models and did not investigate the preventive effects ( Alves et al, 2017 ; Rodrigues et al, 2017 ).…”

“…In line with the current trend of investigating drugs that can control the inflammatory component of OA, pre-clinical studies with SrRan have been performed to test its possible effect in this setting. However, results showing the probable antinociceptive effects of SrRan have conflicted with those of alterations in levels of inflammatory mediators such as TNF-α and IL1-β ( Nunes et al, 2015 ; Alves et al, 2017 ; Mierzwa et al, 2017 ).…”

Stemodia maritima L. Extract Decreases Inflammation, Oxidative Stress, and Alveolar Bone Loss in an Experimental Periodontitis Rat Model

“…Here, we showed that S. maritima (5 mg/kg) significantly increased IL-10 gingival levels, an anti-inflammatory cytokine, while decreasing the pro-inflammatory cytokines TNF-α and CINC-1. Alternative therapeutic approaches based that inhibit TNF-α production have been successfully used for the pre-clinical and clinical treatment of chronic inflammatory diseases, particularly rheumatoid arthritis and temporomandibular joint disorders (Feldmann, 2002 ; Araújo et al, 2013 ; Freitas et al, 2016 ; Alves et al, 2017 ). Further, when mRNA expression for TNF-α, IL-1β, iNOS, and RANK were evaluated, S. maritima 5 mg/kg significantly reduced mRNA expression for all these genes compared to the vehicle group.…”