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低浓度氧/臭氧治疗通过PDE2A-cAMP/cGMP-NF-κB/p65信号通路减轻慢性神经根炎大鼠的神经根炎和机械性异常性疼痛。

Low-Concentration Oxygen/Ozone Treatment Attenuated Radiculitis and Mechanical Allodynia via PDE2A-cAMP/cGMP-NF-B/p65 Signaling in Chronic Radiculitis Rats.

作者信息

Wang Junnan, Wu Mingyi, Lin Xiaowen, Li Yun, Fu Zhijian

机构信息

Department of Pain Management, Shandong Provincial Hospital Affiliated to Shandong University, 324 Jingwu Road, Jinan, Shandong 250021, China.

Department of Anesthesiology, Shandong Provincial Corps Hospital of Chinese People's Armed Police Forces, Jinan, Shandong 250014, China.

出版信息

Pain Res Manag. 2018 Dec 13;2018:5192814. doi: 10.1155/2018/5192814. eCollection 2018.

Abstract

BACKGROUND

Oxygen/ozone therapy is a minimally invasive technique for the treatment of radiculitis from lumbar disc herniation. This study aimed at investigating whether intrathecal administration of low-concentration oxygen/ozone could attenuate chronic radiculitis and mechanical allodynia after noncompressive lumbar disc herniation and at elucidating the underlying mechanisms.

METHODS

First, we transplanted autologous nucleus pulposus into dorsal root ganglions to establish chronic radiculitis in rats. Then, filtered oxygen or oxygen/ozone (10, 20, or 30 g/mL) was intrathecally injected on day 1 after surgery. The ipsilateral paw withdrawal thresholds (PWTs) to mechanical stimuli were tested daily with von Frey filaments. The expression of the tumor necrosis factor- (TNF-) , interleukin- (IL-) 1, IL-6, cyclic adenosine monophosphate (cAMP), cyclic guanosine monophosphate (cGMP), phosphodiesterase 2A (PDE2A), and nuclear factor- (NF-) B/p65 in spinal dorsal horns was measured by enzyme-linked immunosorbent assay, polymerase chain reaction, and western blot on day 7 after surgery.

RESULTS

Chronic radiculitis was established in rats. Intrathecal administration of 10 g/mL, 20 g/mL, or 30 g/mL oxygen/ozone significantly attenuated the decreased mechanical PWTs, downregulated the overexpression of spinal TNF-, IL-1, and IL-6, and increased the expression of cGMP and cAMP in chronic radiculitis rats. In addition, the effects of treatment with 20 g/mL oxygen/ozone were greater than the effects of the 10 g/mL or 30 g/mL doses. Moreover, intrathecal administration of 20 g/mL oxygen/ozone reversed the increased levels of spinal PDE2A and NF-B/p65 mRNA and protein expressions in rats with chronic radiculitis.

CONCLUSION

Intrathecal administration of low-concentration oxygen/ozone alleviated mechanical allodynia and attenuated radiculitis, likely by a PDE2A-cGMP/cAMP-NF-B/p65 signaling pathway in chronic radiculitis rats.

摘要

背景

氧/臭氧疗法是一种用于治疗腰椎间盘突出症所致神经根炎的微创技术。本研究旨在探讨鞘内注射低浓度氧/臭氧是否能减轻非压迫性腰椎间盘突出症后的慢性神经根炎和机械性异常性疼痛,并阐明其潜在机制。

方法

首先,将自体髓核移植到背根神经节以在大鼠中建立慢性神经根炎。然后,在术后第1天鞘内注射过滤后的氧气或氧/臭氧(10、20或30μg/mL)。每天用von Frey细丝测试同侧爪对机械刺激的撤足阈值(PWTs)。在术后第7天,通过酶联免疫吸附测定、聚合酶链反应和蛋白质印迹法测量脊髓背角中肿瘤坏死因子-(TNF-)、白细胞介素-(IL-)1、IL-6、环磷酸腺苷(cAMP)、环磷酸鸟苷(cGMP)、磷酸二酯酶2A(PDE2A)和核因子-(NF-)B/p65的表达。

结果

在大鼠中建立了慢性神经根炎。鞘内注射10μg/mL、20μg/mL或30μg/mL氧/臭氧可显著减轻机械性PWTs的降低,下调脊髓TNF-、IL-1和IL-6的过表达,并增加慢性神经根炎大鼠中cGMP和cAMP的表达。此外,20μg/mL氧/臭氧治疗的效果大于10μg/mL或30μg/mL剂量的效果。而且,鞘内注射20μg/mL氧/臭氧可逆转慢性神经根炎大鼠脊髓中PDE2A和NF-κB/p65 mRNA及蛋白表达水平的升高。

结论

鞘内注射低浓度氧/臭氧可减轻机械性异常性疼痛并减轻神经根炎,可能是通过慢性神经根炎大鼠中的PDE2A-cGMP/cAMP-NF-κB/p65信号通路实现的。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/756c/6311849/4efc86f5d061/PRM2018-5192814.001.jpg

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