Laboratório de Síntese, Reatividade e Avaliação Farmacológica e Toxicológica de Organocalcogênios, Centro de Ciências Naturais e Exatas, Universidade Federal de Santa Maria, Santa Maria, RS, Brazil.
Biol Trace Elem Res. 2013 Sep;154(3):372-8. doi: 10.1007/s12011-013-9736-2. Epub 2013 Jul 3.
Parkinson's disease (PD) patients, in addition to motor dysfunction, also present alterations in pain sensation. The present study characterized the antinociceptive effects of diphenyl diselenide ((PhSe)2) in a model of nociception induced by unilateral, intrastriatal 6-hydroxydopamine (6-OHDA) injection in rats. Male adult Wistar rats received 20 μg/3 μl of 6-OHDA (in saline solution containing 0.02 % of ascorbic acid) or 3 μl of vehicle into the right striatum (1.0 mm anterior, 3.0 mm lateral, and 5.0 mm ventral-with respect to the bregma). Thirty days after injection, rats received (PhSe)2 intragastrically at a dose of 10 mg/kg 1 h before behavioral tests (von Frey hairs, hot plate, tail immersion, formalin, and open field). Our results demonstrated that 6-OHDA injection to rats augmented the response frequency of von Frey hairs (VHF) stimulation, besides reducing the thermal withdrawal latency in the hot plate test. Importantly, the (PhSe)2 treatment decreased the mechanical allodynia measured by the response frequency of VHF stimulation and diminished the thermal nociception in the hot plate test in 6-OHDA-injected rats. In conclusion, these results revealed that a single oral administration of (PhSe)2 1 h prior to the accomplishment of the behavioral tests was effective to attenuate the increased mechanical and thermal nociception caused by a single intrastriatal 6-OHDA injection to rats. Furthermore, other clarifying studies are warranted to improve the evidence bases for future clinical use of (PhSe)2 as a new alternative therapy for the treatment of painful symptoms associated to PD.
帕金森病(PD)患者除了运动功能障碍外,还存在疼痛感觉改变。本研究描述了二苯二硒醚((PhSe)2)在单侧纹状体内注射 6-羟多巴胺(6-OHDA)诱导的疼痛模型中的抗伤害作用。雄性成年 Wistar 大鼠向右侧纹状体(相对于前囟 1.0mm、3.0mm 侧和 5.0mm 腹)注射 20μg/3μl 的 6-OHDA(在含有 0.02%抗坏血酸的盐溶液中)或 3μl 载体。注射后 30 天,大鼠在行为测试前 1 小时经口给予(PhSe)2,剂量为 10mg/kg(PhSe)2。我们的结果表明,6-OHDA 注射到大鼠体内后,增加了冯弗雷毛发(VHF)刺激的反应频率,同时降低了热板试验中的热回避潜伏期。重要的是,(PhSe)2 处理降低了 6-OHDA 注射大鼠的 von Frey 毛发(VHF)刺激反应频率测量的机械性痛觉过敏,并减轻了热板试验中的热伤害感受。总之,这些结果表明,单次口服(PhSe)2 1 小时,在完成行为测试之前,可有效减轻单次纹状体内 6-OHDA 注射引起的大鼠机械性和热伤害感受增加。此外,还需要进一步的澄清研究来提高(PhSe)2 作为治疗与 PD 相关的疼痛症状的新替代疗法的未来临床应用的证据基础。