Effects of intrathecal bupivacaine on the NR2B/CaMKIIα/CREB signaling pathway in the rat lumbar spinal cord

Zhao,Liyan; Zhang,Yonghai; Yang,Fan; Zhu,Di; Li,Ningkang; Zhao,Li; Li,Na; Yu,Jianqiang; Ma,Hanxiang

doi:10.3892/mmr.2018.8448

Effects of intrathecal bupivacaine on the NR2B/CaMKIIα/CREB signaling pathway in the rat lumbar spinal cord

Authors:
- Liyan Zhao
- Yonghai Zhang
- Fan Yang
- Di Zhu
- Ningkang Li
- Li Zhao
- Na Li
- Jianqiang Yu
- Hanxiang Ma
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Affiliations: Department of Anesthesiology, Ningxia Medical University, Yinchuan, Ningxia 750004, P.R. China, Department of Anesthesiology, General Hospital of Ningxia Medical University, Yinchuan, Ningxia 750004, P.R. China, Department of Pharmacology, Ningxia Hui Medicine Modern Engineering Research Center and Collaborative Innovation Center, Ningxia Medical University, Yinchuan, Ningxia 750004, P.R. China
Published online on: January 17, 2018 https://doi.org/10.3892/mmr.2018.8448
Pages: 4508-4514
Copyright: © Zhao et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Neuraxial anesthesia produces an anesthetic-sparing, sedative effect. The mechanism underlying this effect potentially involves decreased spinal afferent input. However, the neurochemical mechanisms at the spinal level remain unknown. The N‑methyl‑D‑aspartate receptor 2B subunit/calcium‑calmodulin‑dependent protein kinase II α/cAMP response element‑binding protein (NR2B/CaMKIIα/CREB) signaling pathway serves an important role in regulating the transmittance of peripheral noxious stimulation to supraspinal regions in the process of nociception. The present study investigated the effects of intrathecal bupivacaine on the NR2B/CaMKIIα/CREB signaling pathway. Following catheterization, 36 male Sprague‑Dawley rats were randomly assigned to a normal saline (NS) or bupivacaine treatment group, in which each rat intrathecally received 20 µl normal saline or 0.5% bupivacaine, respectively. The expression levels of NR2B, CaMKIIα/p‑CaMKIIα, and CREB/phosphorylated (p)‑CREB in the lumbar spinal cord were investigated by western blotting, reverse transcription-quantitative polymerase chain reaction and immunohistochemistry (IHC). Following bupivacaine treatment, western blot analysis demonstrated that the protein expression levels of NR2B, p‑CaMKIIα, and p‑CREB in the spinal cord were reduced by approximately 54, 56 and 33%, respectively, compared with NS control rats. Similar alterations in expression were observed by IHC analysis. Additionally, mRNA expression levels of NR2B, CaMKIIα, and CREB were also downregulated following the intrathecal administration of bupivacaine. Therefore, the sedative effect of subarachnoid blockade with bupivacaine possibly occurs through de‑afferentation, which may reduce cortical arousal by downregulating the spinal NR2B/CaMKIIα/CREB pathway in vivo, however further investigation is required in order to verify this.

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