Antihypersensitivity Effects of Tramadol Hydrochloride in a Rat Model of Postoperative Pain
Antihypersensitivity Effects of Tramadol Hydrochloride in a Rat Model of Postoperative Pain
复制标题
DOI：
10.1213/ane.0b013e31825683c3
复制
发表时间：
2012-08-01
影响因子：
5.7
通讯作者：
Saito, Shigeru
中科院分区：
文献类型：
--
作者：
Kimura, Masafumi;Obata, Hideaki;Saito, Shigeru
背景：曲马多用于治疗各种急性和慢性疼痛。该药物通过2种作用机制诱导镇痛：阿片受体激活和增强去甲肾上腺素（NA）和5-羟色胺（5-HT）传递。然而，尚未评估曲马多对脊髓中NA和5-HT浓度的影响。在本研究中，我们使用大鼠术后疼痛模型研究曲马多的抗过敏作用。我们还评估了增加NA和5-HT水平在脊髓后曲马多注射使用体内microdialysis.METHODS：我们在雄性Sprague-Dawley大鼠（术后疼痛模型）后爪切口。在爪切口后24小时腹膜内和鞘内施用曲马多。通过使用von Frey细丝确定撤回阈值来测量机械超敏性。腹腔注射曲马多后，用微透析法测定腰髓后角NA和5-HT的含量。结果：腹腔注射曲马多（10、20、40 mg/kg）和鞘内注射曲马多（125、250、500 μ g）均能产生剂量依赖性的抗痛敏作用。曲马多的抗超敏反应作用可通过鞘内注射甲麦角酰（30 μ g）（一种5-羟色胺受体拮抗剂）、咪唑烷（30 μ g）（一种去甲肾上腺素受体拮抗剂）和纳洛酮（30 μ g）（一种非选择性阿片受体拮抗剂）进行预处理来预防。微透析结果显示，腹腔注射曲马多20 mg/kg后，脊髓背角5-HT和NA浓度升高，30 min达高峰。此外，NA和5-HT含量在同侧背侧一半的腰脊髓增加1天和3天后爪cutaneous.CONCLUSIONS：这些研究结果表明，曲马多抑制术后超敏反应，增加NA和5-HT水平在脊髓和激活阿片受体。当脊髓NA和5-HT水平升高时，曲马多可能在术后早期更有效。（Anesth Analg 2012;115：443-9）
BACKGROUND: Tramadol is used to treat a wide range of acute and chronic pain. This drug induces analgesia by 2 mechanisms of action: opioid receptor activation and enhancement of noradrenaline (NA) and serotonin (5-HT) transmission. The effect of tramadol on NA and 5-HT concentrations in the spinal cord, however, have not been assessed. In the present study, we investigated the antihypersensitivity effect of tramadol using a rat model of postoperative pain. We also evaluated the increase in NA and 5-HT levels in the spinal cord after tramadol injection using in vivo microdialysis.METHODS: We made a hindpaw incision in male Sprague-Dawley rats (postoperative pain model). Tramadol was administered intraperitoneally and intrathecally 24 hours after paw incision. Mechanical hypersensitivity was measured by determining the withdrawal threshold using von Frey filaments. Microdialysis studies from the dorsal horn of the lumbar spinal cord were performed to measure NA and 5-HT levels after intraperitoneal injection of tramadol. We also measured the NA and 5-HT content in the spinal cord in normal rats and rats with paw incision.RESULTS: Intraperitoneal (10, 20, and 40 mg/kg) and intrathecal (125, 250, and 500 mu g) injection of tramadol produced an antihyperalgesic effect in a dose-dependent manner. The antihypersensitivity effect of tramadol was prevented by intrathecal pretreatment with methysergide (30 mu g), a serotonin receptor antagonist; idazoxane (30 mu g), a noradrenaline receptor antagonist; and naloxone (30 mu g), a nonselective opioid receptor antagonist. Microdialysis study revealed that 5-HT and NA concentrations at the spinal dorsal horn were increased, peaking at 30 minutes after intraperitoneal injection of 20 mg/kg tramadol. Furthermore, the NA and 5-HT content in the ipsilateral dorsal half of the lumbar spinal cord was increased 1 day and 3 days after paw incision, respectively.CONCLUSIONS: These findings indicate that tramadol inhibits postoperative hypersensitivity by increasing NA and 5-HT levels in the spinal cord and activating opioid receptors. Tramadol might be more effective in the early postoperative period when spinal NA and 5-HT levels are increased. (Anesth Analg 2012;115:443-9)