Reliable visceromotor responses are evoked by noxious bladder distention in mice

Reliable visceromotor responses are evoked by noxious bladder distention in mice
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DOI:
10.1097/01.ju.0000116430.67100.8f
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发表时间:
2004-04-01
期刊:
影响因子:
6.6
通讯作者:
Elhefni, H
Elhefni, H
中科院分区:
医学1区
文献类型:
--
作者:
Ness, TJ;Elhefni, H

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目的:建立小鼠膀胱扩张(UBD)急性内脏伤害性感觉模型。小鼠的伤害性模型可以通过遗传模型来研究疼痛和镇痛的机制。材料和方法:异氟醚麻醉,自主呼吸的雌性C3H/J小鼠,经尿道放置24号膀胱内导管,并在腹部肌肉和上肢植入电极,进行肌电和心电图检查。结果:UBD(10~80 mm Hg,20秒,阶段性充气)产生了可靠的、可复制的内脏运动反应(VMRS),即腹部肌肉活动增加,按UBD分级。心率和呼吸反应是可靠的,但不可重复性。皮下注射吗啡(1~4 mg/kg)和膀胱内注射利多卡因(500 mg/kg)对VMR有可逆性抑制作用。膀胱内注入芥子油产生的炎症(2.5%的芥子油与橄榄油对照15分钟)对UBD的敏感度显著增加,UBD强度越低,反应越强烈。VMRS在去大脑的小鼠中存在,但在脊髓横断小鼠中不存在。未麻醉的小鼠对UBD有类似的反应,但VMR的压力阈值较低。结论:这些发现表明目前的模型系统在研究膀胱伤害性感受方面是有用的。在小鼠中,UBD诱发的VMRS是可靠的、可重复性的脊髓球脊髓反射,与刺激有关的分级,被止痛剂抑制,并因炎症的存在而增强。总而言之,这些数据强烈支持使用这一模型,因为它可能允许评估小鼠品系之间的药物遗传差异和使用转基因技术。
Purpose: A mouse model of bladder distension (UBD) induced acute visceral nociception was characterized. Murine models of nociception may allow for the investigation of mechanisms of pain and analgesia through the use of genetic models.Materials and Methods: Isoflurane anesthetized, spontaneously breathing female C3H/J mice had 24 gauge intravesical catheters transurethrally placed and electrodes implanted in the abdominal musculature and in upper limbs for electromyograms and electrocardiograms.Results: UBD (10 to 80 mm Hg for 20 seconds, phasic air distention) produced reliable, reproducible visceromotor responses (VMRs), that is increased abdominal muscle activity, which were graded with graded UBD. Heart rate and respiratory responses were reliable but not reproducible. Subcutaneous morphine (1 to 4 mg/kg) and intravesical lidocaine (500 jig) produced reversible VMR inhibition. Inflammation produced by intravesical mustard oil (2.5% for 15 minutes with an olive oil control) produced a marked increase in sensitivity to UBD with more robust responses evoked by lower UBD intensities. VMRs were present in decerebrate but not in spinal cord transected mice. Unanesthetized mice had similar responses to UBD but with lower pressure thresholds for VMRs.Conclusions: These findings suggest the usefulness of the current model system for the study of bladder nociception. In mice UBD evoked VMRs are spinobulbospinal reflexes that are reliable and reproducible, graded in relation to the stimulus, inhibited by analgesics and augmented by the presence of inflammation. Together these data strongly support the use of this model because it may allow the assessment of pharmacogenetic differences among murine strains and the use of transgenic technologies.