Electroacupuncture alleviates stress-induced visceral hypersensitivity through an opioid system in rats
Electroacupuncture alleviates stress-induced visceral hypersensitivity through an opioid system in rats
复制标题
电针通过阿片类药物系统减轻大鼠应激性内脏超敏反应
DOI：
10.3748/wjg.v18.i48.7201
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发表时间：
2012-12-28
影响因子：
4.3
通讯作者：
Xu, Guang-Yin
中科院分区：
文献类型：
--
作者：
Zhou, Yuan-Yuan;Wanner, Natalie J.;Xu, Guang-Yin
目的：目的：探讨电针是否可以减轻应激诱导的内脏高敏感性，以及电针的作用是否由内源性阿片类物质介导。方法：本研究采用6 ~ 9周龄雄性Sprague-Dawley大鼠。采用4 ℃冷束缚应激45 min、避水应激60 min和强迫游泳应激20 min 3种随机应激源，通过9 d异型间歇应激（HIS）诱导成年雄性大鼠内脏高敏感性。内脏高敏感性的程度通过肌电图或在不同扩张压力（20 mmHg、40 mmHg、60 mmHg和80 mmHg）下结直肠扩张的腹部撤回反射（AWR）评分来量化。AWR评分为0、1、2、3或4，由设盲观察员获得。电针或假电针经典穴ST-36（足三里）或BL-43纳洛酮（ND）或高黄（ND）在某些实验中，对HIS大鼠腹腔注射（methiodide，m-NLX）。HIS大鼠对结直肠扩张的敏感性从6 h开始增加，（第一次测量），维持24 h，并且在不同扩张压力下，与HIS前基线相比，AWR评分在HIS后48 h和7 d恢复到基础水平。20 mmHg、40 mmHg、60 mmHg和80 mmHg扩张压力的HIS前AWR评分分别为0.6 ± 0.2、1.3 ± 0.2、1.9 ± 0.2和2.3 ± 0.2。终止最后一个应激源后6小时，20 mmHg、40 mmHg、60 mmHg和80 mmHg扩张压力下的AWR评分分别为2.0 +/-0.1、2.5 +/- 0.1、2.8 +/- 0.2和3.5 +/- 0.2。与假电针治疗相比，在两后肢的经典穴位ST-36给予电针30分钟显著减弱了HIS大鼠对结肠直肠扩张的过敏反应[20 mmHg下的AWR：2.0 +/- 0.2 vs 0.7 +/- 0.1，P = 4.23 711 E-4; 40 mmHg下的AWR：2.6 +/- 0.2 vs 1.5 +/- 0.2，P = 0.00 163; 60 mmHg下的AWR：3.1 +/- 0.2 vs 1.9 0.1，P = 0.003; 80 mmHg下的AWR：3.6 +/- 0.1 vs 2.4 +/- 0.2，P = 0.0023; 20 mmHg下的肌电图（EMG）：24 +/- 4.7 vs 13.8 +/- 3.5; 40 mmHg时EMG：60.2 +/- 6.6 vs 30 +/- 4.9，P = 0.00 523; 60 mmHg时EMG：83 +/- 10 vs 39.8 +/- 5.9，P = 0.00 029; 80 mmHg时EMG：94.3 ± 10.8 vs 49.6 ± 5.9，P = 0.00 021]。此外，电针BL-43穴并不能减轻HIS大鼠内脏高敏感性。健康大鼠在20和40 mmHg的扩张压力下，电针对结直肠扩张的AWR评分也没有任何影响。在HIS大鼠中，用NLX预处理可阻断EA介导的镇痛作用[用NLX预处理与生理盐水（NS）预处理的AWR评分分别为2.0 vs 0.70 +/- 0.20，2.80 +/- 0.12 vs 1.50 +/- 0.27，对于20 mmHg、40 mmHg、60 mmHg和80 mmHg，3 vs 2.00 +/- 0.15和3.60 +/-0.18 vs 2.60 +/- 0.18;对于20、40、60和80 mmHg，P分别= 0.0087、0.0104、0.0117和0.0188]。此外，EA介导的镇痛作用可被外周限制性阿片受体拮抗剂m-NLX完全逆转（用m-ND预处理的EMG（与NS相比）分别为30.84 +/- 4.39 vs 13.33 +/- 3.88，74.16 +/- 9.04 vs 36.28 +/- 8.01，96.45 +/- 11.80 vs 50.19 +/- 8.28，20 mmHg、40 mmHg、60 mmHg和80 mmHg分别为111.59 ± 13.79 vs 56.42 ± 8.43; P = 0.05 026、0.00 034、0.00 005、0.000 007）。电针经典穴位ST-36可减轻应激性内脏痛，这很可能是由外周阿片途径介导的。(C)2012年百世登。All rights reserved.
AIM: To investigate whether stress-induced visceral hypersensitivity could be alleviated by electroacupuncture (EA) and whether EA effect was mediated by endogenous opiates.METHODS: Six to nine week-old male Sprague-Dawley rats were used in this study. Visceral hypersensitivity was induced by a 9-d heterotypic intermittent stress (HIS) protocol composed of 3 randomly stressors, which included cold restraint stress at 4 degrees C for 45 min, water avoidance stress for 60 min, and forced swimming stress for 20 min, in adult male rats. The extent of visceral hypersensitivity was quantified by electromyography or by abdominal withdrawal reflex (AWR) scores of colorectal distension at different distention pressures (20 mmHg, 40 mmHg, 60 mmHg and 80 mmHg). AWR scores either 0, 1, 2, 3 or 4 were obtained by a blinded observer. EA or sham EA was performed at classical acupoint ST-36 (Zu-San-Li) or BL-43 (Gao-Huang) in both hindlimbs of rats for 30 min. Naloxone (ND) or ND( methiodide (m-NLX) was administered intraperitoneally to HIS rats in some experiments.RESULTS: HIS rats displayed an increased sensitivity to colorectal distention, which started from 6 h (the first measurement), maintained for 24 h, and AWR scores returned to basal levels at 48 h and 7 d after HIS compared to pre-HIS baseline at different distention pressures. The AWR scores before HIS were 0.6 +/- 0.2, 1.3 +/- 0.2, 1.9 +/- 0.2 and 2.3 +/- 0.2 for 20 mmHg, 40 mmHg, 60 mmHg and 80 mmHg distention pressures, respectively. Six hours after termination of the last stressor, the AWR scores were 2.0 +/- 0.1, 2.5 +/- 0.1, 2.8 +/- 0.2 and 3.5 +/- 0.2 for 20 mmHg, 40 mmHg, 60 mmHg and 80 mmHg distention pressures, respectively. EA given at classical acupoint ST-36 in both hindlimbs for 30 min significantly attenuated the hypersensitive responses to colorectal distention in HIS rats compared with sham EA treatment [AWRs at 20 mmHg: 2.0 +/- 0.2 vs 0.7 +/- 0.1, P = 4.23 711 E-4; AWRs at 40 mmHg: 2.6 +/- 0.2 vs 1.5 +/- 0.2, P = 0.00 163; AWRs at 60 mmHg: 3.1 +/- 0.2 vs 1.9 0.1, P = 0.003; AWRs at 80 mmHg: 3.6 +/- 0.1 vs 2.4 +/- 0.2, P = 0.0023; electromyographic (EMG) at 20 mmHg: 24 +/- 4.7 vs 13.8 +/- 3.5; EMG at 40 mmHg: 60.2 +/- 6.6 vs 30 +/- 4.9, P = 0.00 523; EMG at 60 mmHg: 83 +/- 10 vs 39.8 +/- 5.9, P = 0.00 029; EMG at 80 mmHg: 94.3 +/- 10.8 vs 49.6 +/- 5.9, P = 0.00 021]. In addition, EA at the acupuncture point BL-43 with same parameters did not alleviate visceral hypersensitivity in HIS rats. EA in healthy rats also did not have any effect on AWR scores to colorectal distention at distention pressures of 20 and 40 mmHg. The EA-mediated analgesic effect was blocked by pretreatment with NLX in HIS rats [AWR scores pretreated with NLX vs normal saline (NS) were 2.0 vs 0.70 +/- 0.20, 2.80 +/- 0.12 vs 1.50 +/- 0.27, 3 vs 2.00 +/- 0.15 and 3.60 +/- 0.18 vs 2.60 +/- 0.18 for 20 mmHg, 40 mmHg, 60 mmHg and 80 mmHg; P = 0.0087, 0.0104, 0.0117 and 0.0188 for 20, 40, 60 and 80 mmHg, respectively]. Furthermore, EA-mediated analgesic effect was completely reversed by administration of m-NLX, a peripherally restricted opioid antagonist (EMG pretreated with m-ND( vs NS were 30.84 +/- 4.39 vs 13.33 +/- 3.88, 74.16 +/- 9.04 vs 36.28 +/- 8.01, 96.45 +/- 11.80 vs 50.19 +/- 8.28, and 111.59 +/- 13.79 vs 56.42 +/- 8.43 for 20 mmHg, 40 mmHg, 60 mmHg and 80 mmHg; P = 0.05 026, 0.00 034, 0.00 005, 0.000 007 for 20 mmHg, 40 mmHg, 60 mmHg and 80 mmHg, respectively).CONCLUSION: EA given at classical acupoint ST-36 alleviates stress-induced visceral pain, which is most likely mediated by opioid pathways in the periphery. (C) 2012 Baishideng. All rights reserved.