Medical Headquarters, Eisai Co., Ltd., 4-6-10 Koishikawa, Bunkyo-ku, Tokyo 112-8088, Japan.
Division of Neurology and Gerontology, Department of Internal Medicine, School of Medicine, Iwate Medical University, 1-1-1 Idaidori, Yahaba-Cho, Shiwa-Gun, Iwate 028-3694, Japan.
Behav Brain Res. 2023 Aug 24;452:114555. doi: 10.1016/j.bbr.2023.114555. Epub 2023 Jun 22.
Pain is one of the most frequent non-motor symptoms of Parkinson's disease (PD). Neuropathic pain is highly prevalent in PD and negatively affects the quality of life of patients with PD. However, there is currently no evidence-based treatment for its control. Safinamide, a monoamine oxidase (MAO)-B inhibitor with a sodium channel inhibitory effect, showed improvement in PD-related pain in several clinical trials. However, it is unclear for which of the various types of pain in PD safinamide is effective. The aim of the present study was to examine the effect of safinamide on neuropathic pain in a rat model of chronic constriction injury (CCI). Pain was evaluated on postoperative days 14 and 21 using von Frey or weight-bearing tests. Male CCI model rats showed a decreased paw withdrawal threshold and a weight-bearing deficit on postoperative days 14 and 21. Single oral administration of safinamide (15, 30, 45 or 70 mg/kg) dose-dependently improved neuropathic pain in both pain assessments on day 14. Subsequently, the 15 and 45 mg/kg dose groups were administered safinamide orally once daily until day 21. With repeated administration, the effect of safinamide on pain was enhanced. The present findings show that safinamide improves neuropathic pain in male CCI model rats. Further animal model research and pathological and molecular pharmacological investigations are warranted.
疼痛是帕金森病(PD)最常见的非运动症状之一。神经病理性疼痛在 PD 中发病率很高,会对 PD 患者的生活质量产生负面影响。然而,目前针对其控制还没有基于证据的治疗方法。沙芬酰胺是一种具有单胺氧化酶(MAO)-B 抑制作用和钠离子通道抑制作用的药物,在几项临床试验中显示出对 PD 相关疼痛的改善作用。然而,沙芬酰胺对 PD 中哪种类型的疼痛有效尚不清楚。本研究旨在研究沙芬酰胺对慢性缩窄性损伤(CCI)大鼠模型中神经病理性疼痛的影响。术后第 14 天和第 21 天使用 von Frey 或负重试验评估疼痛。雄性 CCI 模型大鼠在术后第 14 天和第 21 天表现出足底撤回阈值降低和负重缺陷。单次口服沙芬酰胺(15、30、45 或 70mg/kg)剂量依赖性地改善了两种疼痛评估方法在第 14 天的神经病理性疼痛。随后,15 和 45mg/kg 剂量组每天口服沙芬酰胺一次,直至第 21 天。重复给药后,沙芬酰胺对疼痛的作用增强。本研究结果表明,沙芬酰胺可改善雄性 CCI 模型大鼠的神经病理性疼痛。需要进一步进行动物模型研究以及病理和分子药理学研究。