Efeito antinocieptivo e sobre a expressão de TNF-α E IL-1β periférica e central de um diterpênico semissintético aplicado localmente na dor aguda da atm de ratos machos e fêmeas

Abstract

The use of plant-based medicines is quite common among the general population to obtain analgesic and anti-inflammatory effects for treating clinical manifestations, such as those occurring in patients with temporomandibular dysfunction (TMD). In this perspective, the semisynthetic diterpenoid derivative SM -2, chemically modified from stemodin, isolated from Stemodia maritima, has shown a promising effect in treating inflammatory pain in the TMJ of rats. Thus, the objective of this study was to evaluate the antinociceptive effect of a semisynthetic diterpenoid applied locally in acute TMJ pain induced by formalin in male and female rats, investigating the possible involvement of peripheral and central exp ression of TNF-α and IL-1β. To this end, 50 rats (Rattus Novergicus), Wistar variety, male and female, weighing between 180 and 240g, with n of 5 animals per tested group, were used. For the study in female rats, the estrous cycle was standardized to proestrus as the reference. The groups were pre-treated (intra-articularly, i.art.) with saline solution (0.9%) or SM -2 (0.02, 0.2, or 2 µL/TMJ) in a volume of 15 µL fifteen minutes later, an i.art. injection of saline solution (0.9%) or formalin (1.5%) in a volume of 15 µL was applied. Nociceptive behavior was evaluated, and subsequently, the animals were euthanized for the removal of the trigeminal ganglion (TG) and caudal subnucleus (CS) for gene expression analysis by qRT-PCR of TNF-α and IL-1β. Data normality was analyzed by the Shapiro-Wilk test, followed by ANOVA with Tukey's post-test. It was observed that SM-2 showed an antinociceptive effect at all three tested doses by reducing nociceptive behavioral response in both male and female rats compa red to the formalin group. In females (0.02 and 0.2 µL/TMJ), SM-2 reduced gene expression of TNF-α and IL-1β in the TG. In the CS, SM-2 reduced gene expression of TNF-α and IL-1β in both male rats (0.2 and 2 µL/TMJ) and female rats (0.02 and 0.2 µL/TMJ). It is concluded that SM-2 administered locally in the TMJ presents an antinociceptive effect with a reduction in gene expression of TNF-α and IL-1β in the peripheral and central nervous systems in females, while in males, this effect was central.