Ação anti-nociceptiva do renaleto de estrôncio na hipernocicepção inflamatória induzido por zymosan na articulação temporomandibular de ratos envolve a inibição de tnfα

Abstract

Temporomandibular joint (TMJ) disorders are associated with inflammatory pain. Strontium ranelate is used in osteoporosis. Though the mechanism of action of Ranelate is unclear, there is evidence of its analgesic effect. We investigate Ranelate efficacy in zymosan-induced TMJ hypernociception in rats evaluating TNF-a, IL-1β, and hemeoxygenase-1 involvement. Wistar rats were pretreated with Ranelate (0.5, 5 or 50mg/kg) before zymosan injection in TMJ. Von Frey test was used to evaluate hypernociception. After zymosan injection synovial lavage was collected for leukocyte counting and myeloperoxidase measurement; joint tissue and trigeminal ganglion for histopathological analysis (H&E), and TNF-a/IL-1β levels dosage (ELISA). To immunohistochemistry, TMJ sections were subjected to both TNF-a/IL-1β antibody. Also, rats were treated with ZnPP-IX (3 mg/kg), a specific HO-1 inhibitor, before Ranelate (0.5 mg/kg). Further, Evans Blue (5 mg/kg) was administered to assess plasma extravasation. Ranelate increased the nociceptive threshold. Although Ranelate was not able to reduce leukocyte counting, myeloperoxidase activity, Evans Blue extravasation, IL-1β levels, and TNF-a/IL-1b immunolabeling, it was effective in reducing TNF-α levels. Further, ZnPP-IX did not changed Ranelate efficacy. Ranelate may achieve its nociceptive-alleviating effects through reducing TNF-α levels in trigeminal ganglion. Further, the Ranelate anti-nociceptive effect is IL-1b and HO-1-independent.