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脉冲射频通过上调神经胶质细胞源性神经营养因子的转录和翻译水平改善慢性缩窄性损伤大鼠的神经病理性疼痛。

Pulsed Radiofrequency Improves Neuropathic Pain in Chronic Constriction Injury Rats through the Upregulation of the Transcription and Translation Levels of Glial Cell Line-Derived Neurotrophic Factor.

机构信息

Department of Anesthesiology and Pain Management, Beijing Tiantan Hospital, Capital Medical University, Beijing, P.R. China.

Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, P.R. China.

出版信息

Pain Physician. 2018 Jan;21(1):33-40.

PMID:29357329
Abstract

BACKGROUND

Several studies in recent years have confirmed that the direct application of pulsed radiofrequency (PRF) on peripheral nerve compression points can alleviate hyperalgesia in animal models of neuropathic pain (NP). However, the mechanism underlying the treatment of peripheral nerves by PRF is unclear.

OBJECTIVES

We aim to observe changes in pain behavior after the application of PRF on the ligation site of the sciatic nerves (SNs) of rats with chronic constriction injury (CCI) and to investigate the effects of PRF on the transcription and translation levels of glial cell line-derived neurotrophic factor (GDNF) in nerve tissues at the treatment site.

STUDY DESIGN

A randomized, experimental trial.

SETTING

Experimental Animal Center, Beijing Tiantan Hospital.

METHODS

Ninety-six adult male Sprague-Dawley rats were randomly divided into 4 groups: sham-sham (SS) group, sham-PRF (SP) group, CCI-sham (CS) group, and CCI-PRF (CP) group. The right SNs of rats in the CS and CP group were ligated to establish the CCI model. The right SNs in the SS and SP groups were isolated and exposed but without being ligated. On the fourteenth day after CCI/sham operation, PRF treatment was performed on the midpoint of the ligation sites of the SN in the CP group and the corresponding sites in the SP group. The electrode was only placed at the ligation sites of the SN in the CS group and the corresponding sites in the SS group without current being applied. The 50% paw withdrawal threshold (50%PWT) and thermal withdrawal latency (TWL) of rats in all of the groups were measured. The transcription and translation levels of GDNF of the PRF/sham treatment sites were measured before and after treatment by reverse transcription-polymerase chain reaction (RT-PCR) and enzyme-linked immunosorbent assays (ELISAs).

RESULTS

The 50%PWT value of the hind paws of rats in the CP group gradually increased on day 6 after the PRF treatment and was significantly higher than that in the CS group (6 days after treatment P < 0.05; 14 days after treatment P < 0.01). The TWL value in the CP group was higher than that in the CS group 2 days after treatment (P < 0.05) and was significantly higher (P < 0.01) from day 6 until the end of the experiment. On the day 6 and 14 after PRF treatment, the mRNA and protein expression levels of GDNF at the ligation sites of the SNs of rats in the CP group were higher than both the levels before treatment and those in the CS group (P < 0.01).

LIMITATIONS

The efficacy of PRF treatment in the CCI model was only tested within 14 days, and the changes in GDNF levels were only tested at 3 time-points before and after treatment.

CONCLUSIONS

The direct application of PRF on SN ligation sites in the CCI model can safely and effectively alleviate NP. One of the mechanisms of this effect could be the upregulation of the transcription and translation of GDNF in compressed SNs.

KEY WORDS

Pulsed radiofrequency, chronic constriction injury, sciatic nerve, 50% paw withdrawal threshold, thermal withdrawal latency, glia cell line-derived neurotrophic factor, reverse transcription-polymerase chain reaction, enzyme-linked immunosorbent assay.

摘要

背景

近年来的几项研究证实,在周围神经压迫点直接应用脉冲射频(PRF)可以减轻周围神经病变性疼痛(NP)动物模型中的痛觉过敏。然而,PRF 治疗周围神经的机制尚不清楚。

目的

观察 PRF 应用于慢性缩窄性损伤(CCI)大鼠坐骨神经(SN)结扎部位后疼痛行为的变化,并探讨 PRF 对治疗部位神经组织中胶质细胞源性神经营养因子(GDNF)转录和翻译水平的影响。

研究设计

随机、实验性试验。

地点

北京天坛医院实验动物中心。

方法

96 只成年雄性 Sprague-Dawley 大鼠随机分为 4 组:假手术-假处理(SS)组、假处理-PRF(SP)组、CCI-假处理(CS)组和 CCI-PRF(CP)组。CCI 模型建立于 CS 和 CP 组大鼠右侧 SN 结扎。SS 和 SP 组大鼠右侧 SN 分离暴露但不结扎。CCI/假手术操作后第 14 天,CP 组右侧 SN 结扎部位中点和 SP 组相应部位行 PRF 治疗,CS 组仅将电极置于 SN 结扎部位,SP 组相应部位不施加电流。测量各组大鼠的右后肢 50%缩足阈值(50%PWT)和热缩足潜伏期(TWL)。采用逆转录-聚合酶链反应(RT-PCR)和酶联免疫吸附试验(ELISA)分别在治疗前后检测 PRF/假处理治疗部位 GDNF 的转录和翻译水平。

结果

CP 组大鼠 PRF 治疗后第 6 天,其右后肢的 50%PWT 值逐渐升高,明显高于 CS 组(治疗后第 6 天 P < 0.05;治疗后第 14 天 P < 0.01)。CP 组大鼠 TWL 于治疗后第 2 天高于 CS 组(P < 0.05),直至实验结束,TWL 均明显高于 CS 组(P < 0.01)。PRF 治疗后第 6 天和第 14 天,CP 组大鼠 SN 结扎部位 GDNF 的 mRNA 和蛋白表达水平均高于治疗前和 CS 组(P < 0.01)。

局限性

PRF 治疗 CCI 模型的疗效仅在 14 天内进行了测试,GDNF 水平的变化仅在治疗前后 3 个时间点进行了测试。

结论

在 CCI 模型中,直接应用 PRF 于 SN 结扎部位可安全有效地缓解 NP。其作用机制之一可能是受压 SN 中 GDNF 的转录和翻译上调。

关键词

脉冲射频;慢性缩窄性损伤;坐骨神经;50%缩足阈值;热缩足潜伏期;胶质细胞源性神经营养因子;逆转录-聚合酶链反应;酶联免疫吸附试验。

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