Avaliação da dor e processo inflamatório na endometriose: uso da talidomida em modelo experimental

Abstract

Introduction: New strategies have been researched for the treatment of endometriosis, such as the use of anti-inflammatory substances of natural origin and drugs that act in the modulation of inflammation. In this context, thalidomide brings evidence related to the decrease in tumor volume and in the count of inflammatory cells and cytokines. Objectives: to evaluate the analgesic, anti-inflammatory and antitumor properties of thalidomide in an experimental model of endometriosis. Methodology: 24 Wistar rats were used and randomly divided into 04 groups containing 06 animals each, as follows: the CONTROL(-) group, with daily administration of 0.5mL of 0.9% saline solution orally; the LEUPROLIDE group, with application of 1mg/kg of leuprolide acetate in a single subcutaneous dose; the T25 group, with oral administration of 25mg/kg of thalidomide dissolved in 0.5mL of 0.9% saline solution and the SHAM group, as a control for the surgical procedure. At moments D0, D7, D14 and D21, tests were performed for clinical evaluation of pain (Rat Grimace Scale, von Frey and Rota Rod); blood samples were collected on D7 and D21, through puncture of the tail vein, for quantification of cytokines (INF γ, TNF α, IL-6 and IL-10); measurements of the volumes of the implants before and at the end of the treatment protocol, and the histopathological study of the implant areas excised moments before euthanasia, were performed. Results: when compared to the control group, a significant reduction in facial pain scores from the fourteenth day onwards (0,83+0,77 vs. 1,77+1,00; with p=0,0021) was obtained by thalidomide ; a significant improvement in gait quality during the entire treatment was also achieved (5,00+0,00 vs. 4,33+0,54; with p<0,001); there was also a significant reduction in INF γ levels at the beginning of treatment (1490,75+357,01 vs. 2066,75+551,65; with p=0,0459), followed by a significant increase in IL-10 at the twentieth first day of the same (218,75+16,24 vs. 137,5+30,59; with p=0,0306). Implant volumes significantly involuted (20,31+9,12 vs. 1,43+1,43; with p=0,0065), as well as histopathological scores reflecting significant involvement of the endometriotic epithelial layer. When compared to leuprolide, in addition to being superior to the cytokine panel, it was similar in terms of volumetric reduction of implants, histological scores and tests that assess pain behavior, except for the evoked nociceptive threshold in which the GnRH analogue was significantly higher. Conclusion: the pleiotropic effects achieved by thalidomide at an oral dose of 25mg/kg for 21 days, showed significant analgesic and antitumor capacity, as well as an important anti-inflammatory profile, suggesting a potential for its applicability in the treatment of endometriosis.