Padronização de um novo modelo de fibromialgia associando salina ácida intramuscular com uma subdose de reserpina em ratos

Abstract

Fibromyalgia (FM) is a syndrome in which individuals experience widespread pain accompa-nied by fatigue, cognitive changes, mood alterations, and sleep disturbances. The complexity of the symptoms involved promotes an ongoing debate regarding its pathophysiological me-chanisms, diagnostic criteria, and treatments. The alterations found in FM can be classified as "Top Down" (without peripheral injury capable of explaining the painful symptoms) and "Bottom Up" (peripheral mechanism of painful activation capable of generating changes in the central nervous system). Studies on FM are made possible through experimental models that allow for a better understanding of the neurobiology and pathophysiological mechanisms of the disease, as well as potential treatments for the problem. FM models using reserpine and acid saline (AS) have been widely used, but they have limitations in fully expressing the complexity of the disease in humans. In this context, the objective of the present study was to verify the effect of peripheral sensory input with AS injected into the muscle in rats subjected to an FM model using a subdose of reserpine. For this purpose, male and female Wistar rats were used, previously approved by the ethics committee (no. 6504200122). The reserpine models (3 doses at 1 mg/kg, subcutaneous) and AS (two injections into the gastrocnemius muscle), previously described in the literature, were characterized. The animals in both mo-dels showed spontaneous nociception, reduced strength and functionality, and reduced anti-oxidant activity in the muscle. However, only the animals that received reserpine showed me-chanical and thermal hyperalgesia, reduced locomotor capacity, depressive-like behavior, and increased inflammatory cytokines in the prefrontal cortex, demonstrating it to be more applicable in mimicking FM-like characteristics compared to the AS model. Furthermore, it was found that both the effect of reserpine and AS produced distinct responses in male and fema-le animals. Rats that received AS showed nociception and reduced strength. Rats from both groups showed impaired short-term memory, a behavior not observed in females. On the other hand, females that received reserpine exhibited depressive-like behavior, a characteris-tic not observed in males of this group. In this study, some positive results were demonstrated in characterizing an FM model induced by injection of a subdose of reserpine associated with AS (including an increase in waking frequency). However, they were not significantly different from the classic FM models of reserpine (1 mg/kg) or AS (two injections). The set of results presented in our work confirms the effectiveness of experimental FM models, with an empha-sis on the reserpine model, as it is able to more accurately mimic the disease symptoms. Further studies should be conducted to improve understanding of the differences between sexes, particularly studies involving molecular and neurochemical evaluations.