Modulation of visceral hyperalgesia by morphine and cholecystokinin from the rat rostroventral medial medulla
Modulation of visceral hyperalgesia by morphine and cholecystokinin from the rat rostroventral medial medulla
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DOI：
10.1016/s0304-3959(02)00469-4
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发表时间：
2003-07-01
期刊：
影响因子：
7.4
通讯作者：
Gebhart, GF
中科院分区：
文献类型：
--
作者：
Friedrich, AE;Gebhart, GF
使用内脏伤害感受模型，我们检查了胆囊收缩素（CCK）是否在大鼠头端腹内侧延髓（RVM）中充当抗阿片肽。由于这种相互作用可能受到炎症的影响，因此对有和没有发炎结肠的大鼠进行了研究。在 RVM 内施用 CCK、CCK 受体拮抗剂和吗啡之前和之后，通过肌电图定量记录对有害性结直肠扩张 (CRD) 的内脏运动反应。实验前 5 天，将 50% 乙醇/盐水（赋形剂）或 2,4,6-三硝基苯磺酸 (TNBS) 滴入结肠，后者会引起结肠发炎。在结肠内赋形剂治疗的大鼠中，RVM 内吗啡剂量依赖性地减弱对 CRD 的反应。在结肠发炎的 TNBS 治疗大鼠中，对 CRD 的反应显着增加，而 RVM 内注射 0.3、3.0 和 6.0 杯剂量的吗啡降低了对对照的反应（即抗痛觉过敏）；测试的最大剂量（30 杯）进一步降低了对 40% 对照的反应。在结肠内载体治疗的大鼠中，用选择性 CCKB（但不是 CCKA）受体拮抗剂进行 RVM 内预处理，剂量依赖性并显着增强低剂量吗啡的效果。 RVM 内 CCK-8 肽增强了结肠内媒介物处理的大鼠对 CRD 的反应，但不是 TNBS 处理的大鼠。 RVM 内纳洛酮对结肠内赋形剂或 TNBS 处理的大鼠没有作用，表明 RVM 中不存在强效阿片类药物活性。这些结果记录了 RVM 中的 CCK-阿片类药物相互作用，表明结肠炎症导致 RVM 中 CCKB 受体的强直活性。 (C) 2003 年国际疼痛研究协会。由 Elsevier Science B.V. 出版。保留所有权利。
Using a model of visceral nociception, we examined whether cholecystokinin (CCK) acts as an anti-opioid peptide in the rat rostral ventromedial medulla (RVM). Because such interaction may be affected by inflammation, rats with and without inflamed colons were studied. The visceromotor response to noxious colorectal distension (CRD), quantified electromyographically, was recorded before and after intra-RVM administration of CCK, CCK receptor antagonists, and morphine. Either 50% ethanol/saline (vehicle) or 2,4,6-trinitrobenzenesulfonic acid (TNBS), which inflames the colon, was instilled into the colon 5 days before experiments.Intra-RVM morphine dose-dependently attenuated responses to CRD in intracolonic vehicle-treated rats. In TNBS-treated rats with inflamed colons, responses to CRD were significantly increased and 0.3, 3.0 and 6.0 mug doses of intra-RVM morphine reduced responses to control (i.e. were anti-hyperalgesic); the greatest dose tested (30 mug) further reduced responses to 40% control. In intracolonic vehicle-treated rats, intra-RVM pre-treatment with a selective CCKB (but not CCKA) receptor antagonist dose-dependently and significantly enhanced the effect of a low dose of morphine. Intra-RVM CCK-8 peptide enhanced responses to CRD in intracolonic vehicle-treated, but not TNBS-treated rats. Intra-RVM naloxone was without effect in intracolonic vehicle-or TNBS-treated rats, suggesting an absence of tonic opioid activity in RVM. These results document a CCK-opioid interaction in RVM, suggesting that colon inflammation leads to tonic activity at CCKB receptors in RVM. (C) 2003 International Association for the Study of Pain. Published by Elsevier Science B.V. All rights reserved.