The present study investigated the effects of intrathecal nefopam on the pain behavior and on the extracellular levels of serotonin (5-HT), norepinephrine (NE), and glutamate in the spinal cord, in a rat model of pain induced by formalin. Nefopam was intrathecally administered 10 min prior to the formalin test to assess its antinociceptive effects. In another cohorts of animals, dihydroergocristine, yohimbine, or (RS)-α-Methylserine-O-phosphate (MSOP), a serotonergic, α-2 adrenergic receptor, or group III metabotropic glutamate receptor antagonist, respectively, were administered prior to the application of nefopam in the formalin test. Microdialysis studies were conducted to measure the extracellular levels of 5-HT, NE, and glutamate in the spinal cord following nefopam administration. Intrathecal nefopam reduced formalin-induced behavior in both phases of the test. The blockade of serotonergic or adrenergic receptors partially reversed the analgesic effects of nefopam in the first phase of the formalin test whereas MSOP reversed these effects in both phases. The microdialysis results revealed that intrathecal nefopam significantly increased 5-HT and NE levels and attenuated the formalin-induced release of glutamate in the spinal cord. Thus, the present data suggest that the increase in the extracellular levels of 5-HT and NE, and reductions in glutamate release in the spinal cord, may have contributed to the analgesic effects of nefopam.

本研究在鞘内福尔马林引起的大鼠疼痛模型中研究了鞘内注射奈福opa对疼痛行为以及脊髓中5-羟色胺（5-HT），去甲肾上腺素（NE）和谷氨酸的细胞外水平的影响。在福尔马林测试前10分钟鞘内注射奈福opa，以评估其抗伤害感受作用。在另一组动物中，在给药之前，分别给予了二氢麦角隐汀，育亨宾或（RS）-α-甲基丝氨酸-O-磷酸酯（MSOP），血清素能，α-2肾上腺素能受体或III组代谢型谷氨酸受体拮抗剂。奈福opa在福尔马林测试中的应用。进行微透析研究以测定给予奈福m后脊髓中5-HT，NE和谷氨酸的细胞外水平。鞘内注射奈福ne可降低福尔马林在测试的两个阶段中的行为。血清素能或肾上腺素能受体的阻滞在福尔马林试验的第一阶段部分逆转了奈福opa的镇痛作用，而MSOP在两个阶段均逆转了这些作用。微透析的结果显示鞘内奈福opa可显着提高5-HT和NE水平，并减弱福尔马林诱导的脊髓中谷氨酸的释放。因此，本数据表明5-HT和NE的细胞外水平的增加以及脊髓中谷氨酸盐释放的减少可能有助于奈福opa的镇痛作用。血清素能或肾上腺素能受体的阻滞在福尔马林试验的第一阶段部分逆转了奈福opa的镇痛作用，而MSOP在两个阶段均逆转了这些作用。微透析的结果显示鞘内奈福opa可显着提高5-HT和NE水平，并减弱福尔马林诱导的脊髓中谷氨酸的释放。因此，本数据表明5-HT和NE的细胞外水平的增加以及脊髓中谷氨酸盐释放的减少可能有助于奈福opa的镇痛作用。血清素能或肾上腺素能受体的阻滞在福尔马林试验的第一阶段部分逆转了奈福opa的镇痛作用，而MSOP在两个阶段均逆转了这些作用。微透析的结果显示鞘内奈福opa可显着提高5-HT和NE水平，并减弱福尔马林诱导的脊髓中谷氨酸的释放。因此，本数据表明5-HT和NE的细胞外水平的增加以及脊髓中谷氨酸盐释放的减少可能有助于奈福opa的镇痛作用。