A combined effect of dextromethorphan and melatonin on neuropathic pain behavior in rats.
A combined effect of dextromethorphan and melatonin on neuropathic pain behavior in rats.
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DOI：
10.1016/j.brainres.2009.06.094
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发表时间：
2009-09-08
期刊：
影响因子：
2.9
通讯作者：
Mao J
中科院分区：
文献类型：
--
作者：
Wang S;Zhang L;Lim G;Sung B;Tian Y;Chou CW;Hernstadt H;Rusanescu G;Ma Y;Mao J
以前的研究表明，褪黑激素到周围神经损伤的对侧的前扣带皮层的管理，防止加重的机械异常性疼痛，同时改善抑郁样行为的Wistar-京都（WKY）大鼠，Wistar大鼠的遗传变异。在本研究中，我们研究了褪黑激素和/或二甲双胍（DM），一种临床上可用的N-甲基-D-天冬氨酸（NMDA）受体拮抗剂，对慢性坐骨神经损伤（CCI）的WKY大鼠疼痛行为的单独与联合治疗的效果。CCI后一周建立疼痛行为（热痛觉过敏和机械性异常性疼痛）。然后用不同剂量的褪黑激素、DM或它们的组合每天一次腹膜内治疗WKY大鼠，持续下一周。在这一周的治疗结束时，在这些相同的大鼠中重复行为测试。虽然DM单独在三个测试剂量（15、30或60 mg/kg）下有效减少热痛觉过敏，但其仅在高剂量（30或60 mg/kg）下减少机械性异常性疼痛。相比之下，仅在本实验中测试的最高剂量（120 mg/kg，而不是30或60 mg/kg）下，单独施用褪黑激素才能有效减少热痛觉过敏。单独的褪黑激素在所有三个测试剂量（30、60和120 mg/kg）下均未能逆转异常性疼痛。然而，褪黑激素（30 mg/kg）和DM（15 mg/kg）的联合腹膜内给药有效地逆转了热痛觉过敏和机械异常性疼痛，尽管单独的每一个单独的剂量没有减少疼痛行为。这些结果表明，褪黑激素与临床上可用的NMDA受体拮抗剂的组合可能比单独使用任一种药物治疗神经性疼痛更有效。
Previous study has shown that administration of melatonin into the anterior cingulate cortex contralateral to peripheral nerve injury prevented exacerbation of mechanical allodynia with a concurrent improvement of depression-like behavior in Wistar-Kyoto (WKY) rats, a genetic variation of Wistar rats. In the present study, we examined the effect of the individual versus combined treatment of melatonin and/or dextromethorphan (DM), a clinically available N-methyl-D-aspartate (NMDA) receptor antagonist, on pain behaviors in WKY rats with chronic constriction sciatic nerve injury (CCI). Pain behaviors (thermal hyperalgesia and mechanical allodynia) were established at one week after CCI. WKY rats were then treated intraperitoneally with various doses of melatonin, DM or their combination once daily for the following week. At the end of this one-week treatment, behavioral tests were repeated in these same rats. While DM alone was effective in reducing thermal hyperalgesia at three tested doses (15, 30 or 60 mg/kg), it reduced mechanical allodynia only at high doses (30 or 60 mg/kg). By comparison, administration of melatonin alone was effective in reducing thermal hyperalgesia only at the highest dose (120 mg/kg, but not 30 or 60 mg/kg) tested in this experiment. Melatonin alone failed to reverse allodynia at all three tested doses (30, 60 and 120 mg/kg). However, the combined intraperitoneal administration of melatonin (30 mg/kg) and DM (15 mg/kg) effectively reversed both thermal hyperalgesia and mechanical allodynia although each individual dose alone did not reduce pain behaviors. These results suggest that a combination of melatonin with a clinically available NMDA receptor antagonist might be more effective than either drug alone for the treatment of neuropathic pain.
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影响因子：
7.4
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ARNER, S;MEYERSON, BA
通讯作者：
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