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鞘内注射奈福泮通过激活涉及脊髓5-HT7而非5-HT3受体的下行5-羟色胺能投射诱导抗伤害感受。

Intrathecal nefopam-induced antinociception through activation of descending serotonergic projections involving spinal 5-HT7 but not 5-HT3 receptors.

作者信息

Lee Hyung Gon, Kim Woong Mo, Kim Joung Min, Bae Hong-Beom, Choi Jeong Il

机构信息

Department of Anesthesiology and Pain Medicine, Chonnam National University, Medical School and Hospital, Gwangju, South Korea.

Department of Anesthesiology and Pain Medicine, Chonnam National University, Medical School and Hospital, Gwangju, South Korea; Brain Korea 21 Plus Project, Chonnam National University Medical School, Gwangju, South Korea.

出版信息

Neurosci Lett. 2015 Feb 5;587:120-5. doi: 10.1016/j.neulet.2014.12.040. Epub 2014 Dec 19.

DOI:10.1016/j.neulet.2014.12.040
PMID:25534502
Abstract

We examined the involvement of spinal 5-HT(5-hydroxytryptamine) receptor 3(5-HT3R) and 7(5-HT7R) as well as the overall role of descending serotonergic projections in the analgesic effects of intrathecal(i.t.) nefopam for two rat models of formalin and paw incision test. I.t. nefopam produced an antinociceptive effect in a dose-dependent manner in both tests. Lesioning the spinal serotonergic projections using i.t. 5,7-dihydroxytryptamine(5,7-DHT) did not influence the intensity of allodynia in the paw incision test, but i.t. 5,7-DHT abolished the effect of nefopam. In the formain test, i.t. 5,7-DHT alone significantly diminished the flinches, but the effect of nefopam was not affected by i.t. 5,7-DHT. Antagonism study showed that i.t. 5-HT7R antagonist, SB269970 significantly blocked the antinociceptive effect of nefopam in both tests, but i.t. 5-HT3R antagonist, ondansetron has no influence on the effect of nefopam. The present study demonstrates that descending spinal serotonergic projections play a vital role in antinociceptive effect of i.t. nefopam in the paw incision test, but indeterminate in the formalin test. In both tests, the antinociceptive effect of i.t. nefopam involves the spinal 5-HT7R, but not 5-HT3R.

摘要

我们研究了脊髓5-羟色胺(5-HT)受体3(5-HT3R)和7(5-HT7R)的参与情况,以及下行5-羟色胺能投射在鞘内注射(i.t.)奈福泮对福尔马林和 paw 切口试验两种大鼠模型镇痛作用中的总体作用。在这两种试验中,鞘内注射奈福泮均以剂量依赖性方式产生抗伤害感受作用。使用鞘内注射5,7-二羟色胺(5,7-DHT)损伤脊髓5-羟色胺能投射,在 paw 切口试验中不影响异常性疼痛的强度,但鞘内注射5,7-DHT消除了奈福泮的作用。在福尔马林试验中,单独鞘内注射5,7-DHT显著减少了退缩反应,但奈福泮的作用不受鞘内注射5,7-DHT的影响。拮抗研究表明,鞘内注射5-HT7R拮抗剂SB269970在两种试验中均显著阻断了奈福泮的抗伤害感受作用,但鞘内注射5-HT3R拮抗剂昂丹司琼对奈福泮的作用没有影响。本研究表明,下行脊髓5-羟色胺能投射在鞘内注射奈福泮对 paw 切口试验的抗伤害感受作用中起重要作用,但在福尔马林试验中作用不确定。在两种试验中,鞘内注射奈福泮的抗伤害感受作用均涉及脊髓5-HT7R,而不涉及5-HT3R。

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