Intrathecal Clonidine: Analgesia and Effect on Opiate Withdrawal in the Rat
Intrathecal Clonidine: Analgesia and Effect on Opiate Withdrawal in the Rat
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DOI：
10.1097/00000542-198501000-00007
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发表时间：
1985-01
期刊：
影响因子：
8.8
通讯作者：
B. Milne;F. Cervenko;K. Jhamandas;M. Sutak
中科院分区：
文献类型：
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作者：
B. Milne;F. Cervenko;K. Jhamandas;M. Sutak
可乐定是一种α2肾上腺素能激动剂，具有镇痛作用，最近已被用于抑制阿片类药物戒断。这两种性质理论上使其成为耐受阿片类药物的患者的合适镇痛替代品。本研究的目的是观察鞘内注射可乐定是否具有镇痛作用，以及它是否能改变脊髓水平的吗啡戒断反应。使用在腰椎蛛网膜下腔长期植入导管的大鼠。在镇痛实验中，鞘内注射可乐定产生镇痛作用，在舔爪试验中的峰值效应出现在200 nM，在甩尾试验中，镇痛作用在100 nM时明显，在400 nM时达到峰值（10 μL林格氏乳酸盐）。在依赖性实验中，吗啡依赖动物（300 mg · kg−1）在吗啡给药后72 h鞘内注射可乐定25、50、200 nM溶于10 μ l乳酸林格氏液中。此后，给予3 mg · kg-1纳洛酮激发并评估戒断情况。可乐定治疗的动物表现出显着的体重减轻和体温下降，高剂量治疗的动物表现出明显的体温过低和后肢松弛。鞘内注射可乐定可预防与阿片类药物戒断相关的痛觉过敏，但不影响大多数行为体征的发生（例如，竖毛、易激惹）与吗啡戒断有关。鞘内注射可乐定可防止戒断过程中纳洛酮引起的血压升高，也可防止未接受吗啡引起的低血压的动物。因此，鞘内注射可乐定具有镇痛作用，可乐定的部分抗戒断作用可能在脊髓水平发挥。
Clonidine, an α2, adrenergic agonist, has analgesic properties and recently has been used to suppress opiate withdrawal. These two properties theoretically make it a suitable analgesic substitute in patients tolerant to opioids. The objectives of this study were to see if intrathecal clonidine is analgesic and whether it can modify morphine withdrawal at the spinal level. Rats chronically implanted with catheters in the lumbar subarachnoid space were utilized. In analgesia experiments, intrathecal clonidine produced analgesia with the peak effect in the paw-lick test occurring at 200 nM, and in the tail-flick test analgesia was apparent at 100 nM and peaked at 400 nM (in 10 μL Ringer's lactate). In dependency experiments, animals dependent on morphine (300 mg · kg−1) received intrathecal clonidine 25, 50, 200 nM in 10 μ1 Ringer's lactate 72 h after morphine. Following this, a naloxone challenge, 3 mg · kg−1 was administered and withdrawal assessed. Clonidine-treated animals showed significant weight loss and decrease in temperature, and those treated with high doses showed marked hypothermia and hind-limb flaccidity. Intrathecal clonidine prevented the hyperalgesia associated with opiate withdrawal but did not affect the occurrence of the majority of behavioral signs (e.g., piloerection, irritability) associated with morphine withdrawal. Intrathecal clonidine prevented the naloxone-induced increase in blood pressure during withdrawal and in animals not treated with morphine-produced hypotension. Thus, intrathecal clonidine is analgesic, and part of the antiwithdrawal action of clonidine may be exerted at the spinal level.