Antinociceptive interaction between spinal clonidine and lidocaine in the rat formalin test: An isobolographic analysis
Antinociceptive interaction between spinal clonidine and lidocaine in the rat formalin test: An isobolographic analysis
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DOI：
10.1213/00000539-200103000-00034
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发表时间：
2001-03-01
影响因子：
5.7
通讯作者：
Iwasaki, H
中科院分区：
文献类型：
--
作者：
Hao, SL;Takahata, O;Iwasaki, H
临床和基础科学研究表明，脊髓α-2-肾上腺素能受体激动剂和局部麻醉剂产生镇痛作用，但α-2-肾上腺素能受体激动剂和局部麻醉剂在持续性疼痛模型中的相互作用尚未研究。在本研究中，我们采用等效线分析法，研究了鞘内注射可乐定和利多卡因在大鼠福尔马林实验中的抗伤害性相互作用。Sprague-Dawley大鼠植入慢性腰椎鞘内导管，并通过福尔马林注射测试缩足。计算双相疼痛行为。在福尔马林前15分钟鞘内注射可乐定（3-12 nmol），在福尔马林前5分钟鞘内注射利多卡因（375-1850 nmol）。为了研究鞘内可乐定和利多卡因的相互作用，采用了等效线设计。脊髓给药可乐定产生剂量依赖性抑制的双相反应，在福尔马林试验。脊髓利多卡因可引起剂量依赖性一过性运动功能障碍，给药后10-15 min运动功能障碍恢复正常。脊髓利多卡因在福尔马林试验中产生剂量依赖性抑制2相活性。等辐射分析表明，鞘内可乐定和利多卡因的组合协同降低2相活性。我们的结论是鞘内可乐定协同利多卡因在减少福尔马林试验中的伤害性反应。
Clinical and basic science studies suggest that spinal alpha -2-adrenergic receptor agonists and local anesthetics produce analgesia, but interaction between alpha -2-adrenergic receptor agonists and local anesthetics in the persistent pain model has not been examined. In the present study, using isobolographic analysis, we investigated the antinociceptive interaction of intrathecal clonidine and lidocaine in the rat formalin test. Sprague-Dawley rats were implanted with chronic lumbar intrathecal catheters, and were tested for paw flinch by formalin injection. Biphasic painful behavior was counted. Intrathecal clonidine (3-12 nmol) was administered 15 min before formalin, and intrathecal lidocaine (375-1850 nmol) was administered 5 min before formalin. To examine the interaction of intrathecal clonidine and lidocaine, an isobolographic design was used. Spinal administration of clonidine produced dose-dependent suppression of the biphasic responses in the formalin test. Spinal lidocaine resulted in dose-dependent transient motor dysfunction and the motor dysfunction recovered to normal at 10-15 min after administration. Spinal lidocaine produced dose-dependent suppression of phase-2 activity in the formalin test. Isobolographic analysis showed that the combination of intrathecal clonidine and lidocaine synergistically reduced Phase-2 activity. We conclude that intrathecal clonidine synergistically interacts with lidocaine in reducing the nociceptive response in the formalin test.