Avaliação do efeito analgésico e anti-inflamatório do biseugenol em modelos de dor e hiperalgesia em ratos

Abstract

Introduction: The discovery of new drugs is crucial to improving the quality of life in chronic diseases and ensuring patient survival. While some medications, such as ibuprofen and diclofenac, COX-1 inhibitors, can cause unwanted side effects, such as gastric toxicity and nephrotoxicity. Therefore, the use of natural products as safe alternatives has been used in order to minimize any potential harm to individuals and reduce their adverse effects. Objective: To evaluate the effect of the biseugenol molecule as an analgesic and anti-inflammatory in models of pain and hyperalgesia in rats. In addition, evaluate the effect of biseugenol on the activation of TRPV1 receptors in primary cultures of rat sensory ganglia. Methods: The effect of the biseugenol molecule as an analgesic and anti-inflammatory in models of pain and hyperalgesia in rats was evaluated. In addition to the effect of biseugenol on the activation of TRPV1 receptors in primary cultures of rat sensory ganglia, changes in resting potential were evaluated by confocal microscopy using the Fluo 3-AM indicator. The biseugenol effect in antagonizing the TRPV1 receptor was evaluated in the dorsal root ganglia, in behavioral tests, these being the capsaicin tests, mechanical hyperalgesia induced by carrageenan injection and volume in paw edema in rats. Results: Previous administration of biseugenol, at concentrations of 10 μM and 100 μM, managed to inhibit the effects of capsaicin on intracellular calcium levels in primary cultures of dorsal root ganglia. Neurons showed a reduced response to capsaicin, while glial cells demonstrated an increase in intracellular calcium after capsaicin administration. In the behavioral test with capsaicin, animals exposed to the highest concentration of biseugenol (50 µM) exhibited a significant reduction in the nociceptive response compared to control animals that received only the capsaicin solution with the vehicle. However, in the mechanical sensitivity test, biseugenol did not have a significant impact on carrageenan-induced hyperalgesia, although it showed a tendency to inhibit hyperalgesia with a dose of 50 µg of biseugenol. When administered alone, biseugenol increased the threshold, suggesting a reduction in the animals' basal mechanical sensitivity. However, in the evaluation of paw edema, intraplantar administration of biseugenol failed to inhibit the development of edema. Conclusions: Based on the results obtained, it is possible to conclude that biseugenol demonstrated the ability to reduce nociception induced by administration of capsaicin in the paw of rats. This suggests a direct analgesic or anesthetic effect on neurons. At concentrations of 10 and 100 µM, biseugenol reduced the activation of the TRPV1 receptor by capsaicin, inhibiting the influx of calcium into nociceptors. Furthermore, it caused an increase in the response of glial satellite cells to the application of capsaicin, which confirms its neuronal effect. Although intraplantar administration of biseugenol appears to induce analgesia, no changes were observed in the paw edema test in rats .