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应用即刻脉冲射频后细胞外信号调节激酶表达与 spared 神经损伤大鼠抗痛觉过敏效应之间的关联

Association between extracellular signal-regulated kinase expression and the anti-allodynic effect in rats with spared nerve injury by applying immediate pulsed radiofrequency.

作者信息

Yeh Chun-Chang, Wu Zhi-Fu, Chen Jui-Chieh, Wong Chih-Shung, Huang Chi-Jung, Wang Jinn-Shyan, Chien Chih-Cheng

机构信息

School of Medicine, Fu Jen Catholic University, New Taipei, 24205, Taiwan.

Department of Anesthesiology & Integrated Pain Management Center, Tri-Service General Hospital and National Defense Medical Center, Taipei, Taiwan.

出版信息

BMC Anesthesiol. 2015 Jun 16;15:92. doi: 10.1186/s12871-015-0071-3.

Abstract

BACKGROUND

The application of pulsed radiofrequency (PRF) close to the dorsal root ganglia, or peripheral nerves, has been demonstrated to be effective for the treatment of chronic neuropathic pain conditions. The goal of this study was to investigate the analgesic effect of immediate PRF treatment after nerve injury and its possible cellular alterations in the dorsal horn of the spinal cord in rats with spared nerve injury (SNI).

METHODS

Neuropathic pain was achieved in a SNI neuropathic pain model by ligating and cutting the common peroneal and tibial branches of the left sciatic nerve, leaving the sural nerve intact. Wistar rats were divided into four groups that received different treatments, i.e., SNI and PRF for 6 min at 45 V (SNI + PRF-45 V), at 60 V (SNI + PRF-60 V), SNI alone, and sham groups. After the SNI surgery, each rat was immediately given the PRF treatment (500 kHz, rate of 2 Hz, 20 ms duration, temperature below 42 °C) on the left sciatic nerve 0.3-0.4 cm proximal to the injured site. The behavioral measurements included mechanical allodynia and cold allodynia of the ipsilateral hind paw and were performed during the 28 days that followed the SNI surgery and PRF treatment. Total extracellular signal-regulated kinase 1 and 2 (ERK1/2) and phospho-ERK1/2 were measured using Western blot in the ipsilateral spinal cord from animals in the different groups.

RESULTS

The three groups of rats with nerve injuries manifested a lower paw withdrawal threshold (PWT) in the behavioral measurement of mechanical allodynia and a shorter painful-behavior duration in the cold allodynia test over 28 days. Mechanical allodynia measurement showed that both the PRF-45 V and PRF-60 V treatment groups exhibited a more prominent antiallodynic effect than did the SNI group from days 1 to 28 after surgery. Similarly, in comparison with the SNI group, both the SNI + PRF-45 V and SNI + PRF-60 V groups had significant inhibition on the cold allodynia measurement from days 1 to 28 after surgery. Furthermore, the activation of the extracellular signal-regulated kinase 1 and 2 (ERK1/2) in the ipsilateral spinal dorsal horn of SNI rats was effectively inhibited in the SNI + PRF-45 V and SNI + PRF-60 V groups for 28 days after surgery.

CONCLUSIONS

Immediate PRF application on the proximal nerve injury site provided a significant inhibition of neuropathic pain formation, accompanied by the inhibition of ERK activation.

摘要

背景

已证明在背根神经节或周围神经附近应用脉冲射频(PRF)可有效治疗慢性神经性疼痛疾病。本研究的目的是探讨神经损伤后立即进行PRF治疗的镇痛效果及其在 spared nerve injury(SNI)大鼠脊髓背角可能的细胞改变。

方法

通过结扎和切断左侧坐骨神经的腓总神经和胫神经分支,保留腓肠神经完整,建立SNI神经性疼痛模型。将Wistar大鼠分为四组,分别接受不同治疗,即SNI和在45V下进行6分钟的PRF治疗(SNI + PRF - 45V)、在60V下进行6分钟的PRF治疗(SNI + PRF - 60V)、单纯SNI组和假手术组。SNI手术后,立即在距损伤部位近端0.3 - 0.4cm处的左侧坐骨神经上对每只大鼠进行PRF治疗(500kHz,2Hz频率,20ms持续时间,温度低于42°C)。行为学测量包括同侧后爪的机械性异常性疼痛和冷异常性疼痛,并在SNI手术和PRF治疗后的28天内进行。使用蛋白质免疫印迹法测量不同组动物同侧脊髓中总的细胞外信号调节激酶1和2(ERK1/2)以及磷酸化ERK1/2。

结果

三组神经损伤大鼠在机械性异常性疼痛的行为学测量中表现出较低的爪撤离阈值(PWT),并且在28天的冷异常性疼痛测试中疼痛行为持续时间较短。机械性异常性疼痛测量显示,PRF - 45V和PRF - 60V治疗组在手术后第1天至第28天均表现出比SNI组更显著的抗异常性疼痛作用。同样,与SNI组相比,SNI + PRF - 45V和SNI + PRF - 60V组在手术后第1天至第28天对冷异常性疼痛测量均有显著抑制作用。此外,SNI + PRF - 45V和SNI + PRF - 60V组在手术后28天有效抑制了SNI大鼠同侧脊髓背角细胞外信号调节激酶1和2(ERK1/2)的激活。

结论

在近端神经损伤部位立即应用PRF可显著抑制神经性疼痛的形成,并伴有ERK激活的抑制。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d066/4467050/2707fd316349/12871_2015_71_Fig1_HTML.jpg

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