Em nosso estudo anterior, os extratos etanólico e aquoso de Crocus sativus provocaram efeitos antinociceptivos no modelo de lesão por constrição crônica (CCI) da dor neuropática. Neste estudo, exploramos os efeitos anti-inflamatório, anti-oxidante e anti-apoptótico de tais extratos em animais CCI. Um total de 72 animais foi dividido em ratos CCI tratados com veículo, grupo de simulação, animais CCI tratados com a dose eficaz de extratos aquoso e etanólico (200 mg / kg, ip). Os níveis de citocinas pró-inflamatórias da medula espinhal lombar, incluindo o fator de necrose tumoral α (TNF-α), a interleucina-1β (IL-1β) e a interleucina 6 (IL-6), foram avaliados nos dias 3 e 7 após a CCI (n = 3, para cada grupo). As alterações de proteínas apoptóticas foram avaliadas nos dias 3 e 7 por western blotting. Marcadores de estresse oxidativo, incluindo malondialdeído (MDA) e glutationa reduzida (GSH), foram medidos no dia 7 após a CCI. Os níveis de citocinas inflamatórias aumentaram em animais CCI nos dias 3 e 7, o que foi suprimido por ambos os extratos. A proporção de Bax / Bcl2 estava elevada no dia 3, mas não no 7° dia, nos animais CCI em comparação com os animais com operação simulada (sham), e diminuíram após o tratamento com ambos os extratos neste momento. Ambos os extratos atenuaram o MDA e aumentaram os níveis de GSH em animais CCI. Pode-se concluir que o açafrão alivia a dor neuropática, pelo menos em parte, por meio de atenuação de citocinas pró-inflamatórias, atividade antioxidante e vias apoptóticas.

In our previous study, the ethanolic and aqueous extracts of Crocus sativus elicited antinociceptive effects in the chronic constriction injury (CCI) model of neuropathic pain. In this study, we explored anti-inflammatory, anti-oxidant and anti-apoptotic effects of such extracts in CCI animals. A total of 72 animals were divided as vehicle-treated CCI rats, sham group, CCI animals treated with the effective dose of aqueous and ethanolic extracts (200 mg/kg, i.p.). The lumbar spinal cord levels of proinflammatory cytokines including tumor necrosis factor α (TNF-α), interleukin-1β (IL-1β) and interleukin 6 (IL-6), were evaluated at days 3 and 7 after CCI (n=3, for each group). The apoptotic protein changes were evaluated at days 3 and 7 by western blotting. Oxidative stress markers including malondialdehyde (MDA) and glutathione reduced (GSH), were measured on day 7 after CCI. Inflammatory cytokines levels increased in CCI animals on days 3 and 7, which were suppressed by both extracts. The ratio of Bax/ Bcl2 was elevated on day 3 but not on day 7, in CCI animals as compared to sham operated animals and decreased following treatment with both extracts at this time. Both extracts attenuated MDA and increased GSH levels in CCI animals. It may be concluded that saffron alleviates neuropathic pain, at least in part, through attenuation of proinflammatory cytokines, antioxidant activity and apoptotic pathways.

OBJECTIVES: The purpose of this work was to determine whether the intraperitoneal administration of glibenclamide as a K ATP channel blocker could have an effect on the antinociceptive effects of antidepressants with different mechanisms of action. METHODS: Three antidepressant drugs, amitriptyline as a dual-action, nonselective inhibitor of noradrenaline and a serotonin reuptake inhibitor, fluvoxamine as a selective serotonin reuptake inhibitor and maprotiline as a selective noradrenaline reuptake inhibitor, were selected, and the effect of glibenclamide on their antinociceptive activities was assessed in male Swiss mice (25-30 g) using a formalin test. DISCUSSION: None of the drugs affected acute nociceptive responses during the first phase. Amitriptyline (5, 10 mg/ kg), maprotiline (10, 20 mg/kg) and fluvoxamine (20 and 30 mg/kg) effectively inhibited pain induction caused by the second phase of the formalin test. Glibenclamide (5 mg/kg) alone did not alter licking behaviors based on a comparison with the control group. However, the pretreatment of animals with glibenclamide (10 and 15 mg/kg) partially reversed the antinociceptive effects of fluvoxamine but not those of maprotiline. In addition, the highest dose of glibenclamide (15 mg/kg) partially prevented the analgesic effect of amitriptyline. CONCLUSION: Therefore, it seems that adenosine triphosphate-dependent potassium channels have a major role in the analgesic activity of amitriptyline and fluvoxamine.