PDF(Pubmed)
Abstract：
Studies have suggested that endoplasmic reticulum stress (ERS) is involved in neurological dysfunction and that electroacupuncture (EA) attenuates neuropathic pain (NP) via undefined pathways. However, the role of ERS in the anterior cingulate cortex (ACC) in NP and the effect of EA on ERS in the ACC have not yet been investigated. In this study, an NP model was established by chronic constriction injury (CCI) of the left sciatic nerve in rats, and mechanical and cold tests were used to evaluate behavioral hyperalgesia. The protein expression and distribution were evaluated using western blotting and immunofluorescence. The results showed that glucose-regulated protein 78 (BIP) and inositol-requiring enzyme 1α (IRE-1α) were co-localized in neurons in the ACC. After CCI, BIP, IRE-1α, and phosphorylation of IRE-1α were upregulated in the ACC. Intra-ACC administration of 4-PBA and Kira-6 attenuated pain hypersensitivity and downregulated phosphorylation of IRE-1α, while intraperitoneal injection of 4-PBA attenuated hyperalgesia and inhibited the activation of P38 and JNK in ACC. In contrast, ERS activation by intraperitoneal injection of tunicamycin induced behavioral hyperalgesia in naive rats. Furthermore, EA attenuated pain hypersensitivity and inhibited the CCI-induced overexpression of BIP and pIRE-1α. Taken together, these results demonstrate that EA attenuates NP by suppressing BIP- and IRE-1α-mediated ERS in the ACC. Our study presents novel evidence that ERS in the ACC is implicated in the development of NP and provides insights into the molecular mechanisms involved in the analgesic effect of EA.
摘要：
研究表明，内质网应激（ERS）与神经功能障碍有关，电针（EA）通过未定义的途径减轻神经性疼痛（NP）。然而,尚未研究ERS在NP前扣带皮质(ACC)中的作用以及EA对ACC中ERS的影响。在这项研究中,通过大鼠左侧坐骨神经慢性压迫性损伤(CCI)建立NP模型,机械和冷试验用于评估行为痛觉过敏。使用蛋白质印迹和免疫荧光评估蛋白质的表达和分布。结果表明，葡萄糖调节蛋白78（BIP）和需要肌醇的酶1α（IRE-1α）共定位在ACC的神经元中。在CCI，BIP之后，IRE-1α,ACC中IRE-1α的磷酸化上调。ACC内给予4-PBA和Kira-6减轻疼痛超敏反应和下调IRE-1α的磷酸化，腹膜内注射4-PBA可减轻ACC中痛觉过敏并抑制P38和JNK的激活。相比之下,腹膜内注射衣霉素激活ERS诱导幼稚大鼠行为痛觉过敏。此外，EA减轻疼痛超敏反应并抑制CCI诱导的BIP和pIRE-1α的过表达。一起来看,这些结果表明，EA通过抑制ACC中BIP和IRE-1α介导的ERS来减弱NP。我们的研究提供了新的证据，表明ACC中的ERS与NP的发展有关，并提供了有关EA镇痛作用的分子机制的见解。
