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奈福泮对链脲佐菌素诱导的糖尿病神经病理性疼痛大鼠的影响。

Effects of nefopam on streptozotocin-induced diabetic neuropathic pain in rats.

机构信息

Department of Anesthesiology and Pain Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.

Department of Anesthesiology and Pain Medicine, Gangneung Asan Hospital, University of Ulsan College of Medicine, Gangneung, Korea.

出版信息

Korean J Pain. 2014 Oct;27(4):326-33. doi: 10.3344/kjp.2014.27.4.326. Epub 2014 Oct 1.

DOI:10.3344/kjp.2014.27.4.326
PMID:25317281
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC4196497/
Abstract

BACKGROUND

Nefopam is a centrally acting non-opioid analgesic agent. Its analgesic properties may be related to the inhibitions of monoamine reuptake and the N-methyl-D-aspartate (NMDA) receptor. The antinociceptive effect of nefopam has been shown in animal models of acute and chronic pain and in humans. However, the effect of nefopam on diabetic neuropathic pain is unclear. Therefore, we investigated the preventive effect of nefopam on diabetic neuropathic pain induced by streptozotocin (STZ) in rats.

METHODS

Pretreatment with nefopam (30 mg/kg) was performed intraperitoneally 30 min prior to an intraperitoneal injection of STZ (60 mg/kg). Mechanical and cold allodynia were tested before, and 1 to 4 weeks after drug administration. Thermal hyperalgesia was also investigated. In addition, the transient receptor potential ankyrin 1 (TRPA1) and TRP melastatin 8 (TRPM8) expression levels in the dorsal root ganglion (DRG) were evaluated.

RESULTS

Pretreatment with nefopam significantly inhibited STZ-induced mechanical and cold allodynia, but not thermal hyperalgesia. The STZ injection increased TRPM8, but not TRPA1, expression levels in DRG neurons. Pretreatment with nefopam decreased STZ-induced TRPM8 expression levels in the DRG.

CONCLUSIONS

These results demonstrate that a nefopam pretreatment has strong antiallodynic effects on STZ-induced diabetic rats, which may be associated with TRPM8 located in the DRG.

摘要

背景

奈福泮是一种中枢作用的非阿片类镇痛药。其镇痛作用可能与单胺再摄取和 N-甲基-D-天冬氨酸（NMDA）受体的抑制有关。奈福泮在急性和慢性疼痛的动物模型以及人类中均显示出了镇痛作用。然而，奈福泮对糖尿病性神经病理性疼痛的作用尚不清楚。因此，我们研究了奈福泮对链脲佐菌素（STZ）诱导的大鼠糖尿病性神经病理性疼痛的预防作用。

方法

在腹腔注射 STZ（60mg/kg）前 30 分钟，腹腔内给予奈福泮（30mg/kg）预处理。在给药前、1 至 4 周后测试机械和冷感觉异常，并进行热痛觉过敏测试。此外，还评估了背根神经节（DRG）中瞬时受体电位锚蛋白 1（TRPA1）和 TRP 中长型 8（TRPM8）的表达水平。

结果

奈福泮预处理显著抑制了 STZ 诱导的机械和冷感觉异常，但不抑制热痛觉过敏。STZ 注射增加了 DRG 神经元中 TRPM8 的表达水平，但不增加 TRPA1 的表达水平。奈福泮预处理降低了 STZ 诱导的 DRG 中 TRPM8 的表达水平。

结论

这些结果表明，奈福泮预处理对 STZ 诱导的糖尿病大鼠具有强烈的抗感觉异常作用，这可能与位于 DRG 中的 TRPM8 有关。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/52cd/4196497/7301420cc398/kjpain-27-326-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/52cd/4196497/09f305e92f4a/kjpain-27-326-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/52cd/4196497/71905f0c5f5b/kjpain-27-326-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/52cd/4196497/89c0b7932fe0/kjpain-27-326-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/52cd/4196497/7301420cc398/kjpain-27-326-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/52cd/4196497/09f305e92f4a/kjpain-27-326-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/52cd/4196497/71905f0c5f5b/kjpain-27-326-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/52cd/4196497/89c0b7932fe0/kjpain-27-326-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/52cd/4196497/7301420cc398/kjpain-27-326-g004.jpg

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