Unidad de Investigación Preclínica, Facultad de Química, Universidad Nacional Autónoma de México, Ciudad Universitaria, México, D.F., 04510, Mexico.
Dirección de Investigaciones en Neurociencias, Instituto Nacional de Psiquiatría "Ramón de la Fuente Muñiz", Calz. México-Xochimilco 101, Col. Sn Lorenzo Huipulco, Mexico, D.F., 14370, Mexico.
Biomed Pharmacother. 2018 Jan;97:310-320. doi: 10.1016/j.biopha.2017.10.077. Epub 2017 Nov 6.
Flavonoids are natural compounds showing anti-hyperalgesic activity in models of pain. Diosmin is a compound poorly studied in the treatment of neuropathic pain. This study evaluates the anti-hyperalgesic actions of diosmin and possible mechanisms of action involved by using a neuropathic pain model in rats. Experimental neuropathic pain was induced by chronic constriction injury (CCI) in male Wistar rats, then aesthesiometric index and plantar tests were assessed to evaluate mechanical and thermal hyperalgesia, respectively, in order to explore the analgesic effects of acute and sub-chronic treatment with diosmin. The GABA, 5-HT, D-like and opioid receptors participation, as well as levels of TNF-α, IL-1β and IL-6, were evaluated in the spinal cord and sciatic nerve tissues after acute and subchronic diosmin administration. In addition, the presence of diosmin on cerebral samples was determined by UHPLC-MS analysis. Acute and sub-chronic treatment with diosmin significantly diminished the mechanical and thermal hyperalgesia induced by CCI in rats. This anti-hyperalgesic effects of diosmin were modified in the presence of naloxone (1mg/kg, i.p.) and haloperidol (0.1mg/kg, i.p.), but not by GABA and 5-HT receptor antagonists. The anti-hyperalgesic effects of diosmin were also linked with reduced levels of TNF-α, IL-1β and IL-6. The presence of diosmin in the cerebral samples was confirmed by chromatographic analysis. In conclusion, our results provide evidence that diosmin produces significant anti-hyperalgesic effects acting at central level by an opioid and D dopaminergic receptors participation, and at peripheral level by reducing proinflammatory cytokines.
类黄酮是一种在疼痛模型中表现出抗痛觉过敏活性的天然化合物。地奥司明是一种在治疗神经性疼痛中研究甚少的化合物。本研究通过在雄性 Wistar 大鼠中建立神经病理性疼痛模型，评估地奥司明的抗痛觉过敏作用及其可能的作用机制。实验性神经病理性疼痛由慢性缩窄性损伤（CCI）引起，然后评估感觉计指数和足底测试，分别评估机械性和热痛觉过敏，以探索急性和亚慢性地奥司明治疗的镇痛作用。在急性和亚慢性地奥司明给药后，评估脊髓和坐骨神经组织中 GABA、5-HT、D 样和阿片受体的参与以及 TNF-α、IL-1β 和 IL-6 的水平。此外，通过 UHPLC-MS 分析确定大脑样本中地奥司明的存在。急性和亚慢性地奥司明治疗显著减轻 CCI 诱导的大鼠机械性和热痛觉过敏。地奥司明的这种抗痛觉过敏作用在纳洛酮（1mg/kg，ip）和氟哌啶醇（0.1mg/kg，ip）存在下被修饰，但不受 GABA 和 5-HT 受体拮抗剂的影响。地奥司明的抗痛觉过敏作用也与 TNF-α、IL-1β 和 IL-6 水平的降低有关。通过色谱分析证实了大脑样本中地奥司明的存在。总之，我们的研究结果提供了证据，表明地奥司明通过参与阿片样物质和 D 多巴胺能受体的中枢作用以及通过减少促炎细胞因子的外周作用产生显著的抗痛觉过敏作用。
