天津医药

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鞘内注射阿片药物复合纳洛酮对切口痛大鼠痛行为学及血浆胃动素的影响

赵军1,高宝柱1,郑宝森2,曹君利3   

  1. 1. 天津市第三中心医院麻醉科
    2. 天津医科大学第二医院疼痛治疗中心
    3. 徐州医学院江苏省麻醉与镇痛应用技术重点实验室
  • 收稿日期:2014-03-05 修回日期:2014-07-17 出版日期:2014-11-15 发布日期:2014-11-15
  • 通讯作者: 高宝柱

Effects of Intrathecal Injection of Opioid Compound with Low-Dose Naloxone on Pain Behavior and Blood Motilin in a Rat Model of Incisional Pain

ZHAO Jun 1,GAO Bao zhu1,ZHENG Bao sen2,CAO Jun li3   

  1. 1. Department of Anesthesiology, the Third Central Hospital of Tianjin Medical University
    2. The Second Affiliated Hospital of Tianjin Medical University
    3. Xuzhou Medical College
  • Received:2014-03-05 Revised:2014-07-17 Published:2014-11-15 Online:2014-11-15
  • Contact: GAO Bao zhu

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摘要： 【摘要】   目的   观察鞘内注射吗啡、芬太尼复合小剂量纳洛酮对切口痛大鼠痛行为学及血浆胃动素（MTL）的影响。   方法   取鞘内置管成功的健康雄性 SD 大鼠 72 只， 随机分为 6 组（n=12）： 生理盐水（NS）组， 切口痛（P）组， 吗啡（5 μg/kg）＋芬太尼（0.25 μg/kg）组（MFP 组）， 吗啡＋芬太尼+纳洛酮 1（0.2 ng/kg）、2（1 ng/kg）、3（5 ng/kg）组（MFPN1、2、3 组）。 后 5 组行足跖肌切口。 各组取其中 6 只于鞘内置管前 24 h（T0）、造模前 24 h（T1）、术后 1 h（T2）、3 h（T3）、6 h（T4）、24 h（T5）、48 h（T6）、72 h（T7）检测机械缩足阈值（PWMT）与热缩足反射潜伏期（PWTL）， 剩余 6 只于术后 6h 即刻断头处死， 取血浆以 ELISA 法检测 MTL 浓度。  结果 MFPN2 组与 NS 组各时点 PWMT 差异无统计学意义，而与 NS 组相比， T2、T5 时点 PWTL 上调（P<0.05）， 其余各时点差异无统计学意义。 P 组、MFPN3 组与 NS 组比较，T2、T3、T4 时点 PWMT、PWTL 显著下调（P<0.05）。 而 MFPN3 组与 P 组比较， T6 时点 PWMT 及 T3、T4 时点 PWTL下调更为显著（P < 0.05）。 P、MFP、MFPN1、MFPN3 组与 NS 组比较， 术后 6 h MTL 表达下调（P < 0.05）。 而 MFPN2与 NS 组 MTL 表达差异无统计学意义。   结论   鞘内注射 1 ng/kg 纳洛酮抑制了吗啡＋芬太尼对切口痛大鼠血浆MTL 表达的影响， 并能上调大鼠热辐射痛阈值， 增强了阿片类药物的镇痛效果。

关键词: 促胃动素, 吗啡, 纳洛酮, 芬太尼, 切口痛, 胃肠动力

Abstract:

[Abstract]   Objective   To investigate effects of intrathecal injection of morphine and fentanyl combined with lowdose naloxone on the pain behavior and the expression of blood motilin (MTL) in the rat model of incisional pain． Methods   A total of 72 healthy male Sprague-Dawley rats (weight 180-220 g), successfully intrathecally catheterized, were randomly divided into 6 groups (n=12 ): normal saline group (NS group), incisional pain group (P group), morphine (5 μg/kg)+ fentanyl (0.25 μg/kg) group (MFP group), morphine+ fentanyl+ naloxone (0.2 ng/kg, 1 ng/kg, 5 ng/kg) group (MFPN1, MF?PN2 and MFPN3 groups). All groups except NS group were made the model of incisional pain on the right plantar surface. At 24-hours before intrathecal cathetherization (T0), 24-hours before modelling (T1), 1-hours (T2), 3-hours (T3) , 6-hours (T4), 24 -hours (T5) , 48-hours (T6) and 72-hours (T7) after modelling respectively, paw withdrawal mechanical threshold (PWMT) and paw withdrawal thermal latency (PWTL) were detected in right hind paw in 6 rats of each group. The other 6 rats in each group were sacrificed 6-hour after operation. The plasma expression of motilin was detected by ELISA.   Results   Compared with NS group, the PWMT was not significantly different in all time points in MFPN2 group. The values of PWTL were significantly longer at T2 and T5 in MFPN2 group than those of NS group (P＜ 0.05)． The PWMT and the PWTL were significantly decreased at T2, T3 and T4 in P and MFPN3 groups than those of NS group (P＜ 0.05)． Compared with P group, the PWMT at T6, and PWTL at T3 and T4 were significantly decreased in MFPN3 group (P<0.05). The MTL at T6 was significantly decreased in P, MFP, MFPN1 and MFPN3 groups compared with that of NS group (P<0.05). There was no significant difference in MTL between MFPN2 group and NS group (P>0.05)． Conclusion   In the rat model of incisional pain, intrathecal injection of naloxone at 1 ng/kg can inhibit the down-regulation of blood motillin caused by morphine and fentanyl, and which can up-regulate the PWTL, enhancing the analgesic effects of opioids．

Key words: motilin, morphine, naloxone, fentanyl, incisional pain, gastrointestinal dynamics