加巴喷丁的抗伤害作用及其在实验动物研究中的作用机制。

BACKGROUND & OBJECTIVES: Several studies have shown the possible analgesic effects of gabapentin, widely used as an antiepileptic. Thus, clinical studies have been carried out especially for neuropathic syndroms. This study was undertaken to investigate experimentally whether gabapentin has analgesic effects in mice and rats.

METHODS

The mice were divided into 10 groups (n=7) with various treatments to assess central and peripheral antinociceptive activity of gabapentin. Hot plate, tail clip and tail flick tests were applied for the investigation of central antinociceptive activity and the writhing test was applied for the investigation of peripheral antinociceptive activity. In addition, we also evaluated the levels of PGE 2 and nNOS on perfused hippocampus slices of rats.

RESULTS

Gabapentin showed a peripheral antinociceptive effect at all doses and a central antinociceptive effect at 30mg/kg dose. While the L-NAME and cyproheptadine changed the central and peripheral effects of gabapentin, naloxone did not change these effects. In vitro studies showed that gabapentin significantly increased nNOS level. PGE 2 and nNOS were found to have an important role in the antinociceptive effects of gabapentin at all doses and its combinations with L-NAME, cyproheptadine, indomethacine, and naloxone. As expected, PGE 2 levels decreased in all groups, while nNOS levels increased, which is believed to be an adaptation mechanism.

INTERPRETATION & CONCLUSIONS: Our findings indicate that arachidonate, nitrergic and serotonergic systems play an important role in the antinociceptive activity of gabapentin except for the opioidergic system. Additionally, this effect occured centrally and peripherally. These effects were also mediated by nNOS and PGE2.

背景与目的

已有多项研究表明，广泛用于抗癫痫的加巴喷丁可能具有镇痛作用。因此，已经进行了专门针对神经病变综合征的临床研究。本研究旨在实验性地研究加巴喷丁在小鼠和大鼠中是否具有镇痛作用。

方法

将小鼠分为 10 组（n=7），进行各种处理，以评估加巴喷丁的中枢和外周镇痛活性。应用热板、尾巴夹和尾巴闪烁测试来研究中枢镇痛活性，应用扭体测试来研究外周镇痛活性。此外，我们还评估了大鼠灌流海马切片中 PGE 2 和 nNOS 的水平。

结果

加巴喷丁在所有剂量下均表现出外周镇痛作用，在 30mg/kg 剂量下表现出中枢镇痛作用。虽然 L-NAME 和赛庚啶改变了加巴喷丁的中枢和外周作用，但纳洛酮没有改变这些作用。体外研究表明，加巴喷丁显著增加了 nNOS 水平。在所有剂量下，以及与 L-NAME、赛庚啶、吲哚美辛和纳洛酮联合使用时，均发现 PGE 2 和 nNOS 对加巴喷丁的镇痛作用具有重要作用。如预期的那样，所有组中的 PGE 2 水平均降低，而 nNOS 水平升高，这被认为是一种适应机制。