Casein and its pepsin and trypsin hydrolysates of goat milk reduces temporomandibular joint inflammatory hypernociception in rats: Putative role for TNF-α, IL-1β, and IL-10

Temporomandibular Disorders (TMDs) is a group of musculoskeletal and neuromuscular conditions involving the temporomandibular joints (TMJs), the masticatory muscles and all associated tissues. As there are no records on the activity related to proteins derived from goat milk involving inflammation in the TMJs, this study investigated the antinociceptive activity of casein (FCN), obtained by isoelectric precipitation of goat milk at pH 4.1, and its hydrolysates, obtained by hydrolysis with pepsin and trypsin (HDP and HDT, respectively). Pre-treatment with casein (1 mg/kg), HDP (1 mg/kg), or HDT (1 mg/kg) significantly reduced the nociceptive behavioral response (56.8 ± 9.17; 78 ± 8.28; and 86.0 ± 5.91, respectively) significantly reduced the nociceptive behavioral response, when compared to formalin group (177.7 ± 3.96). Although the efficacy of hydrolysates is independent of the HO-1 and NO pathways, their antinociceptive efficacy appear to depend on TNFα, IL-1β and IL-10 involvement. In fact, both HDP and HDT reduced TNF-α and Il-1β immunistaining in synoviocytes from synovial membranes and in trigeminal ganglion. Regarding IL-10, HDP increased IL-10 immunistaining in the synoviocytes from the TMJ synovial membrane and in the intercellular matrix. Also, HDT increased IL-10 immunistaining in both synovial membrane and trigeminal ganglion. Taken together our data suggest that the efficacy of casein fraction and its hydrolysates of goat milk in formalin-induced TMJ inflammatory hypernociception in rats involves, at least in part, TNF-α and IL-1β inhibition, and IL-10 secretion. Thus, considering the safety profile of goat milk, we postulated that CNF, HDP, and HDT, could offer a novel way to treat TMJ pain.