A型肉毒素复合低剂量加巴喷丁对切口痛大鼠脊髓背角神经激肽-1受体内化的影响

doi:10.3969/j.issn.1006-7795.2017.03.001

首都医科大学学报 ›› 2017, Vol. 38 ›› Issue (3): 331-335.doi: 10.3969/j.issn.1006-7795.2017.03.001

A型肉毒素复合低剂量加巴喷丁对切口痛大鼠脊髓背角神经激肽-1受体内化的影响

利雪阳, 王云, 孙雨晴, 马丹旭, 吴安石, 岳云

首都医科大学附属北京朝阳医院麻醉科, 北京 100020

收稿日期:2017-03-20 出版日期:2017-05-21 发布日期:2017-06-14
通讯作者: 王云 E-mail:pandedao@126.com
基金资助:
国家自然科学基金（81571065，81428008，81400909）。

Effects of botulinum toxin A combined with low dose gabapentin on the NK-1 receptor internalization at spinal cord dorsal horn in rats with incisional pain

Li Xueyang, Wang Yun, Sun Yuqing, Ma Danxu, Wu Anshi, Yue Yun

Department of Anesthesiology, Beijing Chaoyang Hospital, Capital Medical University, Beijing 100020, China

Received:2017-03-20 Online:2017-05-21 Published:2017-06-14
Supported by:
This study was supported by National Natural Science Foundation of China(81571065, 81428008, 81400909).

摘要/Abstract

摘要： 目的评价A型肉毒素复合低剂量加巴喷丁对切口痛大鼠行为学及脊髓背角神经激肽-1（neurokinin-1，NK-1）受体内化的影响。方法雄性SD大鼠，体质量280~300 g，6~8周龄。采用数字表法随机分为5组（n=9）：对照组（Control组）、切口痛-盐水组（Saline组）、切口痛-加巴喷丁组（GBP组）、切口痛-毒素组（BoNT/A组）、切口痛-毒素复合加巴喷丁组（G+B组）。BoNT/A组和G+B组于造模前1 d鞘内注射BoNT/A 0.5U，GBP组和G+B组于造模前30 min鞘内注射GBP 50 mg。切口痛模型制备后3 h，每组各随机抽取6只进行累计疼痛评分（cumulative pain scores，CPS）和机械缩足阈值（paw withdrawal threshold，PWT）的测量；每组各抽取3只，通过免疫荧光技术测定NK-1受体内化情况。结果与Control组比较，切口后3 h Saline组、GBP组、BoNT/A组和G+B组右后足CPS升高、PWT降低、脊髓背角NK-1受体内化神经元数目上调（P<0.05）；与Saline组比较，BoNT/A组和G+B组CPS降低、PWT升高、脊髓背角NK-1受体内化神经元数目下调（P<0.05），GBP组差异无统计学意义（P>0.05）；与BoNT/A组比较，G+B组CPS降低、PWT升高、脊髓背角NK-1受体内化神经元数目下调（P<0.05）。结论单独应用低剂量GBP对大鼠切口痛无效，BoNT/A复合低剂量GBP治疗切口痛大鼠的术后疼痛有明显的协同作用，疗效优于单独应用BoNT/A，其镇痛机制可能与抑制切口痛大鼠脊髓背角NK-1受体内化有关。

关键词: A型肉毒杆菌毒素, 加巴喷丁, 疼痛, 神经激肽1受体, 脊髓

Abstract: Objective To evaluate the effects of botulinum toxin A combined with low dose gabapentin on the neurokinin-1 (NK-1) receptor internalization at spinal cord dorsal horn in rats with incisional pain. Methods Male Sprague-Dawley rats, weighing 280-300 g, aged 6-8 weeks, were used in the study. Rats were randomly selected and divided into 5 groups (n=9 each) using a random number table:control group (Control group), incisional pain group (Saline group), gabapentin group (GBP group), botulinum toxin A group (BoNT/A group), botulinum toxin A combined with gabapentin group (G+B group). At 24 h before operation, botulinum toxin A 0.5U (in 10 mL of normal saline) was injected intrathecally in BoNT/A group and G+B group. At 30 min before operation, gabapentin 50 mg was injected intrathecally in GBP group and G+B group. At 3 h after operation, 6 rats in each group were selected to measure the cumulative pain scores (CPS) and mechanical paw withdrawal threshold (PWT) in the right hindpaw; besides, 3 rats in each group were selected and sacrificed, and the lumbar segment (L4,5) of the spinal cord was removed for determination of the expression of NK-1 receptors in the spinal dorsal horn by immunofluorescence. Results Compared with Control group, the CPS was significantly increased, the PWT was significantly decreased, and the expression of NK-1 receptors in the spinal dorsal horn was significantly up-regulated in Saline group, GBP group, BoNT/A group and G+B group at 3 h after operation(P<0.05). Compared with Saline group, the CPS was significantly decreased, the PWT was significantly increased, and the expression of NK-1 receptors in the spinal dorsal horn was significantly down-regulated in BoNT/A group and G+B group at 3 h after operation (P<0.05), and no significant change was found in group GBP (P>0.05). Compared with BoNT/A group, the CPS was significantly decreased, the PWT was significantly increased, and the expression of NK-1 receptors in the spinal dorsal horn was significantly down-regulated in G+B group at 3 h after operation (P<0.05). Conclusion Low doses of gabapentin alone may have no effect on postoperative pain, but when it is coadministrated with BoNT/A, it can greatly enhance the analgesic effect of BoNT/A. The analgesic mechanism may be due to inhibition of the internalization of NK-1 receptor at spinal cord horn in a rat model of incisional pain.

Key words: botulinum toxin type A, gabapentin, pain, neurokinin-1 receptors, spinal cord

中图分类号:

R971

利雪阳, 王云, 孙雨晴, 马丹旭, 吴安石, 岳云. A型肉毒素复合低剂量加巴喷丁对切口痛大鼠脊髓背角神经激肽-1受体内化的影响[J]. 首都医科大学学报, 2017, 38(3): 331-335.

Li Xueyang, Wang Yun, Sun Yuqing, Ma Danxu, Wu Anshi, Yue Yun. Effects of botulinum toxin A combined with low dose gabapentin on the NK-1 receptor internalization at spinal cord dorsal horn in rats with incisional pain[J]. Journal of Capital Medical University, 2017, 38(3): 331-335.

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A型肉毒素复合低剂量加巴喷丁对切口痛大鼠脊髓背角神经激肽-1受体内化的影响

Effects of botulinum toxin A combined with low dose gabapentin on the NK-1 receptor internalization at spinal cord dorsal horn in rats with incisional pain

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