Abstract Gabapentin has antihyperalgesic action, decreasing central sensitization in neuropathic pain models; this effect depends on the mobilization of endogenous pain control pathways. This study aims to investigate the contribution of the endocannabinoid system to the antihyperalgesic action of gabapentin. Mus musculus Swiss, male, were submitted to PSL. On the 7th and 14th days post PSL, different groups were treated with CB1 receptor antagonist, AM281 via i.t. (2 μg/5 μl) or i.pl. (10 μg/20 μl) or CB2, AM630 via i.t. (5 μL i.t.) or (20 μL i.p.) and 15 min after gabapentin (30 mg / kg orally). Mechanical hyperalgesia was measured by the frequency of paw removal by the von Frey monofilament. Gabapentin demonstrated antihypernociceptive action, which was attenuated in animals pretreated with AM281 in both the i.t. and i.pl routes on the 7th and 14th days, differently from animals pretreated with AM630 that did not achieve a significant reduction with administration i.t. only on the 14th day with administration i.pl. The results show that endocannabinoid system contributes to the antihyperalgesic action of gabapetin in neuropathic pain by PSL, suggesting participation in the medullary and peripheral levels of CB1 receptors, and the peripheral performance of CB2 receptors.

Abstract Citrus species are widely related to antihyperalgesic and anti-inflammatory effects. The aim of this study was to investigate if treatment with ethanolic extract from peels of mature Citrus reticulata Blanco causes antihyperalgesic effects on the referred mechanical hyperalgesia in a model of dextran sulphate of sodium (DSS)-induced colitis in mice, as well as the possible oxidative damage in different regions of the brain induced by its inflammatory reaction. Antihyperalgesia (30 to 300 mg/kg) was investigated by behavioral response (frequency of response to von Frey filament stimulation) in Swiss mice, while damage to central nervous system was investigated through techniques that evaluated oxidative stress using male black C57 BL6 mice (n=8). Treatment of the animals with the extract (100 mg/kg) from days 3 to 5 after colitis induction reduced referred the mechanical hyperalgesia (32.6 ± 5.1) in relation to the control group (57.4 ± 2.0). Levels of lipid peroxidation or carbonyl proteins were augmented in colitis-induced animals in relation to the disease group. These results indicated an antihyperalgesic effect of the studied extract and a potential impairment of the central nervous system functioning caused by inflammation during colitis, which could be related to mental disorders observed in patients suffering of this pathology.