Influência da inflamação gerada pela obesidade no perfil nociceptivo de ratos e ratas com osteoartrite e o exercício de curto prazo como modulador inflamatório para a analgesia

Abstract

Obesity is a disease characterized by the accumulation of adipose tissue, which leads to a chronic inflammatory process due to the systemic release of inflammatory cytokines. Likewise osteoarthritis (OA) also presents itself as an inflammatory disorder. Thus, obesity induction studies should be used to understand the effects of obesity on OA, as well as to identify possible treatments such as physical exercise that have anti-inflammatory characteristics. Thus, the aim of this thesis was to verify the role of inflammation generated by obesity on the nociceptive profile of rats and rats with OA and to evaluate the effects of acute physical exercise on inflammation. Therefore, the thesis was divided into 3 studies starting with the induction of obesity, where the animals received high-fat (HF) and cafeteria (CAF) diets for 60 days. In step 2, males and females were divided into control groups (CM and CF), non-obese with OA (MP and FP), obese (OM and OF) and obese with OA (OMP and OFP). The MP, OMP, FP and OFP groups were submitted, on the 59th day, to OA induction by intra-articular injection of sodium monoiodoacetate (MIA) in the right knee (1.5mg/50μL) and followed up until day 65. Na third stage, again males and females were divided into groups equal to those of stage 2, however, in this stage, the groups treated with swimming exercise were added (for 5 consecutive days, 24h after OA induction): control (CM-EX and CF-EX), non-obese with OA (MP-EX and FP-EX), obese (OM-EX and OF-EX) and obese with OA (OMP-EX and OFP-EX). The animals were evaluated for their body weight and mechanical, thermal and spontaneous pain nociceptive profile. In addition, to measure obesity, the adiposity index was used. At the end of 60 days (study 1) and 65 days (study 2 and 3), euthanasia was performed and whole blood was collected by cardiac puncture to assess hematological, biochemical, and inflammatory cytokine parameters. Statistical analysis was performed using one- or two-way analysis of variance (ANOVA) with multiple comparisons with Tukey post hoc, paired t-test and correlation with linear regression, and the results were considered statistically significant at p<0.05 . The results obtained show that the groups with obesity induction by the CAF diet showed an increase in body weight and adiposity index compared to the control group. In addition, it was observed that obese animals showed changes in the thermal and mechanical nociceptive profile. Furthermore, the results show that the obese groups had a significant increase in the systemic release of inflammatory cytokines (TNF-α, IL-1β, IL-6, IL-8, leptin) and a reduction in anti-inflammatory ones (IL-10 and adiponectin) . When associated with OA in the OMP and OFP groups, there was an increase in the inflammatory process and pain. In study 3, after the exercise protocol, there was a reduction in inflammatory cytokines that was related to a decrease in pain. Thus, it can be concluded that obesity causes changes in the nociceptive profile due to the inflammatory process, which, in turn, is related to the retention of adipose tissue. In conditions of association of obesity with OA, this inflammatory process is exacerbated and with it, there is also an increase in pain. In this context, acute physical exercise has been shown to be able to positively modulate inflammation and thus resulted in pain reduction. Although the OMP-EX and OFP-EX animals presented reduced levels of inflammation and pain, when compared to the MP-EX, FP-EX, OM and OF groups, they remained with higher levels of inflammation and pain. Thus, the need for specific therapies for obese individuals with associated inflammatory diseases is demonstrated.