Caseína e seus hidrolisados de pepsina e tripsina do leite de cabra reduzem a hipernocicepção inflamatória da articulação temporomandibular em ratos: papel para TNF- -α, IL-1β E IL-10

Abstract

Pain is a complex and multifaceted experience that can affect the orofacial region. The temporomandibular joint (TMJ) is one of the structures that can be affected, resulting in a clinical condition of the disabling course, such as temporomandibular disorders (TMD). Pharmacotherapy has been used in the treatment of TMDs, however, due to the limited effectiveness and important adverse effects, it makes possible the search for new drugs. Goat milk is a food matrix of high nutritional value and with properties that have been evaluated. The objective of the study was to investigate the antinociceptive and antiinflammatory effect of the casein fraction of goat milk (CNF) and two hydrolysates, from its hydrolysis with pepsin (HDP) and trypsin (HDT), in a model of hypernociception induced by formalin in the TMJ of rats. For this purpose, male Wistar rats (180-240 g, n = 5) were pre-treated (per os) with CNF (1 mg / kg), HDP (1 mg / kg) and HDT (1 mg / kg). After 60 minutes, an intraarticular injection (a.i.) of saline solution (50 μL, 0.9%) was applied in the control group or formalin (50 μL, 1.5%) in the left TMJ. The nociceptive response was measured by quantifying, in seconds, the act of the mouse scratching the left TMJ region and by the number of times to raise the head reflexively over the 45 minutes period. Then, the animals were perfused with general anesthesia, followed by the removal of the TMJ and the trig eminal ganglion (TG) for immunohistochemical analysis by TMA for cytokines TNFα, IL -1β and IL-10. In addition, we investigated the roles of hemeoxygenase-1 (HO-1) and nitric oxide (NO) pathways in the antinociceptive mechanism of action of hydrolysates. The results showed that the three samples studied showed antinociceptive effects by reducing the nociceptive behavioral response. HDP and HDT have an antinociceptive and anti-inflammatory effect independent of the HO -1 and NO pathways, but can reduce the cytokines TNFα, IL-1β and increase IL-10 in TMJ and TG. The HDP and HDT compounds, therefore, have antinociceptive and anti-inflammatory activity mediated by the cytokines TNFα, IL -1β and IL-10.