Analysis of the antinociceptive effect of systemic administration of tramadol and dexmedetomidine combination on rat models of acute and neuropathic pain

Analysis of the antinociceptive effect of systemic administration of tramadol and dexmedetomidine combination on rat models of acute and neuropathic pain
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DOI:
10.1016/j.pbb.2007.06.006
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发表时间:
2007-11-01
影响因子:
3.6
通讯作者:
Uyar, Mehmet
Uyar, Mehmet
中科院分区:
心理学4区
文献类型:
--
作者:
Guneli, Ensari;Yavasoglu, N. Ulkue Karabay;Uyar, Mehmet

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本研究的目的是探讨曲马多和右美托咪定单独或联合全身给药对大鼠急性和神经性疼痛模型的可能的抗伤害性作用。采用甩尾法和热板法观察曲马多(520 mg/kg)和右美托咪定(5 ~ 20 μ g/kg)腹腔注射以及曲马多+右美托咪定3种不同组合(分别为5 + 5、5 + 10和10+ 5,mg/kg+ μ g/kg)对急性疼痛的镇痛作用。采用热足底试验,观察曲马多(5 μ g/kg)、右美托咪定(5 μ g/kg)、曲马多+右美托咪定联合(5 + 5)对坐骨神经结扎所致神经性疼痛的影响。在旋转记录仪上评估镇静/运动不协调。曲马多和右美托咪定在甩尾和热板试验中产生剂量相关的抗痛感。在这两项试验中,这些药物联合使用产生的抗伤害感受效果比曲马多产生的效果更大。或者在几个时间点单独使用右美托咪定。热板试验中曲马多+右美托咪定联合(5 + 10)的抗伤感受效果最强,甩尾试验中曲马多+右美托咪定联合(10 + 5)的抗伤感受效果最显著。在神经性疼痛中,曲马多+右美托咪定联合(5 + 5)的抗感觉作用也明显大于单独应用。在rotarod试验中,曲马多(30和40 mg/kg)、右美托咪定(30和40 μ g/kg)、曲马多+右美托咪定联合(10+10、20+20)产生镇静/运动不协调,而曲马多(5-20 mg/kg)、右美托咪定(5-20 μ g/kg)和曲马多+右美托咪定联合(5 + 5、5 +10和10+ 5)对镇静/运动不协调无影响。曲马多和右美托咪定联合使用比单独使用这两种药物更有效地提高急性和神经性疼痛的痛阈。(C) 2007爱思唯尔公司版权所有。
The aim of the present study was to investigate the possible antinociceptive effect of systemic administration of tramadol and dexmedetomidine either alone or in combination on acute and neuropathic pain models in rats. The antinociceptive effects of intraperitoneal (i.p.) tramadol (520 mg/kg) and dexmedetomidine (5-20 mu g/kg) and three different combinations of tramadol+dexmedetomidine (5 + 5, 5 + 10 and 10+ 5, mg/kg+ mu g/kg, respectively) were measured by tail-flick and hot-plate methods in acute pain. The effects on the sciatic nerve ligation-induced neuropathic pain was tested by i.p. administration of tramadol (5 mu g/kg), dexmedetomidine (5 mu g/kg) and tramadol + dexmedetomidine combination (5 + 5) using a thermal plantar test. Sedation/motor-incoordination was assessed on rotarod. Tramadol and dexmedetomidine produced dose-related antinociception in tail-flick and hot-plate tests. In both tests, combination of these drugs produced an antinociceptive effect that is greater than that produced by tramadol. or dexmedetomidine alone at several time points. In hot-plate test, tramadol + dexmedetomidine combination (5 + 10) exerted the strongest antinociceptive effect, while tramadol + dexmedetomidine combination (10 + 5) was significantly most effective in tail-flick test. In the neuropathic pain, the antinociceptive effect exerted by tramadol + dexmedetomidine combination (5 + 5) was also significantly greater than their applications alone. In rotarod test, tramadol (30 and 40 mg/kg), dexmedetomidine (30 and 40 mu g/kg), tramadol+dexmedetomidine combination (10+10, 20+20) produced sedation/motor-incoordination, whereas tramadol (5-20 mg/kg), dexmedetomidine (5-20 mu g/kg) and tramadol + dexmedetomidine combination (5 + 5, 5 + 10 and 10 + 5) did not produce any effect on sedation/motor-incoordination. The combination of tramadol and dexmedetomidine was more effective in increasing the pain threshold in acute and neuropathic pain when compared with the administration of either of these drugs alone. (C) 2007 Elsevier Inc. All rights reserved.