Lab of Neuropharmacology and Neurotoxicology, Shanghai University, Shanghai 200444, PR China.
Biochem Biophys Res Commun. 2013 Oct 25;440(3):374-80. doi: 10.1016/j.bbrc.2013.09.071. Epub 2013 Sep 21.
Intraplantar (i.pl.) injection of BmK I, a receptor site 3-specific modulator of voltage-gated sodium channels (VGSCs) from the venom of scorpion Buthus martensi Karsch (BmK), was shown to induce long-lasting and spontaneous nociceptive responses as demonstrated through experiments utilizing primary thermal and mirror-imaged mechanical hypersensitivity with different time course of development in rats. In this study, microglia was activated on both sides of L4-L5 spinal cord by i.pl. injection of BmK I. Meanwhile, the activation of p38/MAPK in L4-L5 spinal cord was found to be co-expressed with OX-42, the cell marker of microglia. The unilateral thermal and bilateral mechanical pain hypersensitivity of rat induced by BmK I was suppressed in a dose-dependent manner following pretreatment with SB203580 (a specific inhibitor of p-p38). Interestingly, microglia activity was also reduced in the presence of SB203580, which suggests that BmK I-induced microglial activation is mediated by p38/MAPK pathway. Combined with previously published literature, the results of this study demonstrate that p38-dependent microglial activation plays a role in scorpion envenomation-induced pain-related behaviors.
足底（i.pl.）注射来自蝎子 Buthus martensi Karsch（BmK）毒液的电压门控钠离子通道（VGSCs）受体 3 特异性调节剂 BmK I，已被证明可诱发持久的自发性痛觉反应，这通过利用原发性热和镜像机械超敏反应实验在大鼠中表现出不同的发展过程。在这项研究中，BmK I 的足底注射激活了 L4-L5 脊髓两侧的小胶质细胞。同时，发现 L4-L5 脊髓中的 p38/MAPK 激活与 OX-42 共表达，OX-42 是小胶质细胞的细胞标志物。BmK I 诱导的大鼠单侧热和双侧机械痛敏在 SB203580（p-p38 的特异性抑制剂）预处理后呈剂量依赖性抑制。有趣的是，SB203580 存在时小胶质细胞活性也降低，这表明 BmK I 诱导的小胶质细胞激活是由 p38/MAPK 通路介导的。结合以前发表的文献，这项研究的结果表明，p38 依赖性小胶质细胞激活在蝎子毒液引起的疼痛相关行为中起作用。
