Dipartimento di Medicina Pubblica Clinica e Preventiva, Seconda Università di Napoli, 80138 Naples, Italy.
Neurosci Lett. 2012 Nov 14;530(1):85-90. doi: 10.1016/j.neulet.2012.08.088. Epub 2012 Sep 12.
The role of the purinergic system in the modulation of pain mechanisms suggests that it might be promising target for treating neuropathic pain. In this study we evaluated the effects of two different dialdehydic compounds: a modified stable adenosine (2-[1-(6-amminopurin-9-il)-2-osso-etossi]prop-2-enale, named MED1101), and oxidized ATP (Ox-ATP), in two different neuropathic pain rat models: the sciatic spared nerve injury (SNI) and paclitaxel evoked painful peripheral neuropathy (pPPN). Neuropathic animals were divided in groups as follows: (a) treated with intraperitoneal (i.p.) MED1101 or Ox-ATP for 21 days; (b) receiving vehicle (VEH) and (c) control (CTR) rats. The allodynic and hyperalgesic behavior was investigated by Von Frey filament test and thermal Plantar test, respectively. We evaluated by immunocytochemistry the astrocytic (GFAP) and microglial (Iba1) response on lumbar spinal cord sections. In either experimental models and using either substances, treated animals showed reduced allodynia and thermal hyperalgesia paralleled by a significant reduction of glial reaction in the spinal cord. These data prompt to hypothesize a potential role of dialdehydes as analgesic agent in chronic neuropathic pain and a possible role as anti-gliotic molecules.
嘌呤能系统在调节疼痛机制中的作用表明，它可能是治疗神经病理性疼痛的有前途的靶点。在这项研究中，我们评估了两种不同的二醛化合物：一种改良的稳定腺苷（2-[1-（6-氨基嘌呤-9-基）-2-亚砜基-乙氧基]丙烯醛，命名为 MED1101）和氧化 ATP（Ox-ATP），在两种不同的神经病理性疼痛大鼠模型中的作用：坐骨神经 spared 神经损伤（SNI）和紫杉醇诱发的痛性周围神经病（pPPN）。神经病理性动物分为以下几组：（a）腹腔注射（i.p.）MED1101 或 Ox-ATP 治疗 21 天；（b）接受载体（VEH）和（c）对照（CTR）大鼠。用 Von Frey 纤维试验检测痛觉过敏和热板试验检测痛觉过敏行为。我们通过免疫细胞化学评估腰椎脊髓切片中星形胶质细胞（GFAP）和小胶质细胞（Iba1）的反应。在这两种实验模型中，使用这两种物质的治疗动物表现出痛觉过敏和热痛觉过敏减轻，同时脊髓中的神经胶质反应明显减少。这些数据提示二醛类化合物可能作为慢性神经病理性疼痛的镇痛剂发挥作用，也可能作为抗神经胶质分子发挥作用。
