Interaction of Morphine and Selective Serotonin Receptor Inhibitors in Rats Experiencing Inflammatory Pain
Interaction of Morphine and Selective Serotonin Receptor Inhibitors in Rats Experiencing Inflammatory Pain
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DOI：
10.3346/jkms.2012.27.4.430
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发表时间：
2012-04-01
影响因子：
4.5
通讯作者：
Park, Jong Yeon
中科院分区：
文献类型：
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作者：
Lee, Byung-Sang;Jun, In-Gu;Park, Jong Yeon
西酞普兰和帕罗西汀是选择性血清素再摄取抑制剂，也具有镇痛作用。我们在完全弗氏佐剂（CFA）诱导外周炎症的大鼠模型中研究了鞘内注射吗啡、西酞普兰、帕罗西汀及其组合的抗痛觉过敏和抗痛觉过敏作用。通过直接腰椎穿刺进行鞘内给药。使用动态足底感觉计测量机械异常性疼痛。通过测量响应辐射热和冷水的缩爪潜伏期来确定热痛觉过敏和冷异常疼痛。在鞘内注射之前和之后 15、30、45 和 60 分钟进行行为测试。足底内注射 CFA 产生机械异常性疼痛、热痛觉过敏和冷异常性疼痛。鞘内注射吗啡（0.3或1μg）具有抗异常疼痛或抗痛觉过敏作用（升高24.0%-71.9%）。当添加西酞普兰（100μg）和帕罗西汀（100μg）的组合时，吗啡的作用显着增强（升高35.2％-95.1％）。纳洛酮和美西麦角逆转了这种上升趋势。纳洛酮和美西麦角也逆转了西酞普兰和帕罗西汀的作用。我们认为μ阿片受体和5-羟色胺受体在吗啡、西酞普兰、帕罗西汀及其组合在经历炎性疼痛的动物中产生抗异常疼痛和抗痛觉过敏作用中起主要作用。
Citalopram and paroxetine are selective serotonin reuptake inhibitors and also have antinociceptive effects. We investigated the antiallodynic and antihyperalgesic effects of intrathecally administered morphine, citalopram, paroxetine, and combinations thereof, in a rat model in which peripheral inflammation was induced by complete Freund's adjuvant (CFA). Drugs were intrathecally administered via direct lumbar puncture. Mechanical allodynia was measured using a Dynamic Plantar Aesthesiometer. Thermal hyperalgesia and cold allodynia were determined by measuring latency of paw withdrawal in response to radiant heat and cold water. Behavioral tests were run before and 15, 30, 45, and 60 min after intrathecal injection. Intraplantar injection of CFA produced mechanical allodynia, thermal hyperalgesia, and cold allodynia. Intrathecally administered morphine (0.3 or 1 mu g) had antiallodynic or antihyperalgesic effects (24.0%-71.9% elevation). The effects of morphine were significantly increased when a combination of citalopram (100 mu g) and paroxetine (100 mu g) was added (35.2%-95.1% elevation). This rise was reversed by naloxone and methysergide. The effects of citalopram and paroxetine were also reversed by naloxone and methysergide. We suggest that the mu opioid receptor and serotonin receptors play major roles in production of the antiallodynic and antihyperalgesic effects of morphine, citalopram, paroxetine, and combinations thereof, in animals experiencing inflammatory pain.