Intrathecal Infusion of Pyrrolidine Dithiocarbamate for the Prevention and Reversal of Neuropathic Pain in Rats Using a Sciatic Chronic Constriction Injury Model
Intrathecal Infusion of Pyrrolidine Dithiocarbamate for the Prevention and Reversal of Neuropathic Pain in Rats Using a Sciatic Chronic Constriction Injury Model
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鞘内注射吡咯烷二硫代氨基甲酸酯预防和逆转坐骨神经慢性缩窄性损伤模型大鼠的神经性疼痛
DOI：
10.1097/aap.0b013e3181df245b
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发表时间：
2010-05-01
影响因子：
5.1
通讯作者：
Wang, Yun-Jiao
中科院分区：
文献类型：
--
作者：
Pan, Yun-Dan;Guo, Qu-Lian;Wang, Yun-Jiao
背景和目的：最近的研究表明，核因子-kappa B(NE-kappa B)可能在神经损伤性神经病理性疼痛中发挥作用。在此，我们观察了鞘内注射去甲肾上腺素kappa B抑制剂吡咯烷二硫代氨基甲酸酯(PDTC)对坐骨神经慢性狭窄损伤(CCI)模型大鼠神经病理性疼痛、脊髓小胶质细胞激活和CX3CR1表达的影响。方法：在氯醛麻醉下，雄性SD大鼠(300-350g)安装鞘内导管，进行坐骨神经CCI或假手术。CCI前1d或后3d鞘内注入生理盐水或PDTC(100或1000pmol/d)(n=8)。分别于手术前和CCI后第1~7天测定大鼠对机械刺激的后爪撤退阈值和对辐射热的撤退潜伏期。用OX-42免疫反应检测脊髓小胶质细胞的激活，用Western blotting检测脊髓CX3CR1的表达。结果：慢性牵张性损伤引起机械痛觉过敏和热痛敏，小胶质细胞激活，OX-42的表达表现出来。鞘内注射PDTC对脊髓组织学无明显影响，但可阻止机械性和热敏性痛觉过敏的发展，抑制神经损伤诱导的小胶质细胞活化和脊髓CX3CR1的表达。结论：鞘内注射PDTC对CCI诱导的大鼠伤害性行为具有保护作用。NF-kappaB通路的激活可能参与了脊髓小胶质细胞的激活和CX3CR1的上调。(Reg Anesth Pain Med 2010；35：231-237)
Background and Objectives: Recent studies have suggested that nuclear factor kappa B (NE-kappa B) may play a role in mediating nerve injury-induced neuropathic pain. Here, we examined the effects of intrathecal pyrrolidine dithiocarbamate (PDTC), a NE-kappa B inhibitor, on the development of neuropathic pain, spinal microglial activation, and CX3CR1 expression induced by sciatic chronic constriction injury (CCI) model in rats.Methods: Under chloral hydrate anesthesia, male Sprague-Dawley rats (300-350 g) fitted with intrathecal catheters underwent either sciatic CCI or sham surgery. Intrathecal saline or PDTC (100 or 1000 pmol/d) was infused I day before or 3 days after CCI (n 8). The rat hind-paw withdrawal threshold to mechanical stimuli and withdrawal latency to radiant heat were determined before surgery and from days I to 7 after CCI. Spinal microglial activation was evaluated with OX-42 immunoreactivity, and spinal CX3CR1 expression was assessed by Western blotting.Results: Chronic constriction injury induced mechanical allodynia and thermal hyperalgesia and microglial activation as demonstrated by OX-42 expression. Whereas it had no apparent effect on spinal cord histology, intrathecal administration of PDTC prevented the development of the mechanical and thermal hyperalgesia and inhibited nerve injury induced microglial activation and spinal CX3CR1 expression.Conclusions: In this study, we have shown the protective effect of intrathecal PDTC on the development of nociceptive behaviors induced by CCI in rats. The activation of NF-kappa B pathway may contribute to spinal microglial activation and CX3CR1 up-regulation. (Reg Anesth Pain Med 2010;35: 231-237)