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鞘内注射舒芬太尼和蛋白激酶C抑制剂对神经病理性疼痛大鼠痛阈及脊髓背角NMDA受体/CGRP表达的影响

[Effect of intrathecal sufentanil and protein kinase C inhibitor on pain threshold and the expression of NMDA receptor/ CGRP in spinal dorsal horn in rats with neuropathic pain].

作者信息

Wang Yichun, Guo Qulian, Wang Mingde, Wang E, Zou Wangyuan, Zhao Jianghong

机构信息

Department of Anesthesiology, Xiangya Hospital, Central South University, Changsha 410008, China.

出版信息

Zhong Nan Da Xue Xue Bao Yi Xue Ban. 2012 Aug;37(8):783-9. doi: 10.3969/j.issn.1672-7347.2012.08.005.

DOI:10.3969/j.issn.1672-7347.2012.08.005
PMID:22954912
Abstract

OBJECTIVE

To investigate the effect of intrathecal sufentanil and protein kinase C inhibitor on pain threshold and the expression of N-methyl-D-aspartate receaptors (NMDAR)/calcitonin generelated peptide (CGRP) in spinal dorsal horn in rats with neuropathic pain.

METHODS

Fifty-four healthy male Sprague-Dawley rats were randomly divided into 6 groups (9 in each group). The rats in the sham group(Group S) + spared nerve injury (SNI), SP+SNI, and P+SNI were intrathecally injected sufentanil (1 μg), sufentanil (1 μg) and chelerythrine chloride (11 μg), chelerythrine chloride (11 μg) followed by 10 μL normal saline once every day for 14 days postoperatively, respectively. Similarly, rats in the control group (Group C), the sham group (Group S), and SNI model group (Group SNI) were intrathecally injected 20 μL normal saline in the uniform interval. Pain behaviours were measured on Day 1 pre-surgery and on Day 1, 2, 7, and 14 after the intrathecal injection. The expressions of NMDAR and CGRP in the spinal dorsal horn of L5 segment were determined by immunohistochemistry on Day 2, 7, and 14 after the intrathecal injection.

RESULTS

Compared with Group C and Group S, mechanical allodynia threshold in group SNI was decreased after the surgery (P<0.01), and expressions of NMDAR and CGRP immunoreactive soma in the spinal dorsal horn was significantly increased (P<0.01). Mechanical stimulation pain threshold was elevated in Group S+SNI, Group P+SNI, and Group SP+SNI compared with Group SNI (P<0.01), while expressions of NMDAR and CGRP immunoreactive soma in Group S+SNI, Group P +SNI, and Group SP+SNI were significantly decreased (P<0.05 or 0.01).

CONCLUSION

Intrathecal administration of sulfentanil and protein kinase C inhibitor can provide significant antinociception in rats with neuropathic pain and obviously inhibit the upregulation of NMDAR and CGRP expressions in the spinal dorsal horn of SNI rat models.

摘要

目的

探讨鞘内注射舒芬太尼及蛋白激酶C抑制剂对神经病理性疼痛大鼠痛阈及脊髓背角N-甲基-D-天冬氨酸受体(NMDAR)/降钙素基因相关肽(CGRP)表达的影响。

方法

将54只健康雄性Sprague-Dawley大鼠随机分为6组(每组9只)。假手术组(S组)、鞘内注射舒芬太尼(1μg)+ spared神经损伤(SNI)组(S+SNI组)、鞘内注射舒芬太尼(1μg)及氯化白屈菜红碱(11μg)+SNI组(SP+SNI组)、鞘内注射氯化白屈菜红碱(11μg)+SNI组(P+SNI组),术后每天分别鞘内注射相应药物1次,连续14天,每次10μL。对照组(C组)、假手术组(S组)、SNI模型组(SNI组)则每隔相同时间鞘内注射20μL生理盐水。于术前1天及鞘内注射后第1、2、7、14天测量疼痛行为。鞘内注射后第2、7、14天采用免疫组化法检测L5节段脊髓背角NMDAR和CGRP的表达。

结果

与C组和S组比较,SNI组术后机械性异常性疼痛阈值降低(P<0.01),脊髓背角NMDAR和CGRP免疫反应阳性胞体表达明显增加(P<0.01)。与SNI组比较,S+SNI组、P+SNI组、SP+SNI组机械刺激痛阈升高(P<0.01),S+SNI组、P+SNI组、SP+SNI组脊髓背角NMDAR和CGRP免疫反应阳性胞体表达明显降低(P<0.05或0.01)。

结论

鞘内注射舒芬太尼及蛋白激酶C抑制剂对神经病理性疼痛大鼠有明显的镇痛作用,可明显抑制SNI大鼠模型脊髓背角NMDAR和CGRP表达上调。

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