Department of Anesthesiology, Xiangya Hospital, Central South University, Changsha; National Clinical Research Center for Geriatric Disorders, Central South University, Changsha, Hunan.
Eur J Histochem. 2021 Mar 12;65(1):3184. doi: 10.4081/ejh.2021.3184.
Previous studies have suggested that pyrrolidine dithiocarbamate (PDTC), a nuclear factor κB (NF-κB) inhibitor, play a role in deterring nerve injury-induced neuropathic pain (NP) The activation of NF-κB pathway may contribute to spinal microglial activation, CX3CR1 and tumor necrosis factor-alpha (TNF-a) up-regulation. The aim of this study was to clarify whether PDTC could inhibit the development of neuropathic pain via decreasing TNF-a-induced CX3CR1 up-regulation. Sprague-Dawley rats were randomly divided into sham group and NP group. Rats in each group were treated with intrathecal infusion of PDTC (100 or 1000 pmol/d) or saline. The sciatic nerve chronic constriction injury (CCI) model was used to induce NP in rats. Mechanical stimuli and radiant heat were used to evaluate mechanical allodynia and thermal hyperalgesia. Spinal microglial marker OX42 and TNF-a were detected by immunohistochemistry. In vitro BV-2 microglia activation was induced by TNF-a incubation, and the levels of CX3CR1 were assessed by Western blot and reverse transcription-polymerase chain reaction. Pain behavior and immunohistochemistry results showed that intrathecal infusion of PDTC at 100 or 1000 pmol/d prevented the development of mechanical and thermal hyperalgesia, spinal microglial activation and TNF-a expression induced by sciatic nerve CCI in rats. In vitro experiment results showed that PDTC inhibited the TNF-a-induced CX3CR1 up-regulation in BV-2 microglial cells. In conclusion, intrathecal infusion of PDTC could attenuate the pain-related behaviors induced by sciatic nerve CCI through suppressing the spinal microglia activation and TNF-a up-regulation in rats. The NF-κB activation might be responsible for TNF-a-induced CX3CR1 up-regulation in microglia.
先前的研究表明，吡咯烷二硫代氨基甲酸盐（PDTC），一种核因子 κB（NF-κB）抑制剂，在阻止神经损伤引起的神经性疼痛（NP）方面发挥作用。NF-κB 通路的激活可能有助于脊髓小胶质细胞的激活、CX3CR1 和肿瘤坏死因子-α（TNF-a）的上调。本研究旨在阐明 PDTC 是否可以通过降低 TNF-a 诱导的 CX3CR1 上调来抑制神经性疼痛的发展。SD 大鼠随机分为假手术组和 NP 组。每组大鼠接受鞘内输注 PDTC（100 或 1000 pmol/d）或生理盐水。使用坐骨神经慢性缩窄损伤（CCI）模型诱导大鼠 NP。使用机械刺激和辐射热评估机械性痛觉过敏和热痛觉过敏。通过免疫组织化学检测脊髓小胶质细胞标志物 OX42 和 TNF-a。通过 TNF-a 孵育诱导 BV-2 小胶质细胞活化，并通过 Western blot 和逆转录-聚合酶链反应评估 CX3CR1 水平。疼痛行为和免疫组织化学结果表明，鞘内输注 100 或 1000 pmol/d 的 PDTC 可预防坐骨神经 CCI 诱导的机械性和热痛觉过敏、脊髓小胶质细胞激活和 TNF-a 表达的发展。体外实验结果表明，PDTC 抑制了 TNF-a 诱导的 BV-2 小胶质细胞中 CX3CR1 的上调。总之，鞘内输注 PDTC 可通过抑制大鼠脊髓小胶质细胞的激活和 TNF-a 的上调来减轻坐骨神经 CCI 引起的疼痛相关行为。NF-κB 的激活可能负责 TNF-a 诱导的小胶质细胞中 CX3CR1 的上调。
