An objective approach to assess colonic pain in mice using colonometry.

An objective approach to assess colonic pain in mice using colonometry.
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用结肠测量法客观评估小鼠结肠疼痛的方法。

DOI:
10.1371/journal.pone.0245410
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发表时间:
2021
期刊:
影响因子:
3.7
通讯作者:
Madar J
Madar J
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Qiao LY;Madar J

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本研究提出了一种非手术方法,用来评估小鼠结肠机械敏感性,这是一种通过记录生理盐水以恒定速率注入远端结肠期间的结肠内压来测量结肠牵张反射收缩的技术。人体计量学记录已被用于评估健康人和神经疾病患者的结肠功能。在这里,我们发现比色法也可以在小鼠身上实施,最佳的生理盐水输注速度为1.2毫升/小时。比色法显示,周期性的结肠收缩引起的间歇性压力上升。在2,4,6-三硝基苯磺酸诱导的结肠炎、初级传入神经元的化学激活或结直肠扩张伤害性刺激后立即产生的结肠超敏现象中,结肠内压的幅度显著升高,并伴有较快的压力升高(ΔP/Δt)。结肠超敏反应相关的AICP值升高是结肠牵张反射收缩强度增强的结果,这反映了结肠感觉反射通路的活动增强。结肠超敏反应的ΔP/Δt值升高,提示结肠机械感觉阈值降低,在较短的输液时间内,较小的生理盐水输注量可引起结肠牵张反射收缩。抑制由Nav1.8表达细胞控制的初级传入通路可减弱肿瘤坏死因子受体诱导的AICP、ΔP/Δt上调和结肠疼痛行为对慢性阻塞性肺疾病的反应。这些发现支持柱状图可以用来分析小鼠的结肠疼痛。
The present study presents a non-surgical approach to assess colonic mechanical sensitivity in mice using colonometry, a technique in which colonic stretch-reflex contractions are measured by recording intracolonic pressures during saline infusion into the distal colon in a constant rate. Colonometrical recording has been used to assess colonic function in healthy individuals and patients with neurological disorders. Here we found that colonometry can also be implemented in mice, with an optimal saline infusion rate of 1.2 mL/h. Colonometrograms showed intermittent pressure rises that was caused by periodical colonic contractions. In the sceneries of colonic hypersensitivity that was generated post 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced colonic inflammation, following chemogenetic activation of primary afferent neurons, or immediately after noxious stimulation of the colon by colorectal distension (CRD), the amplitude of intracolonic pressure (AICP) was markedly elevated which was accompanied by a faster pressure rising (ΔP/Δt). Colonic hypersensitivity-associated AICP elevation was a result of the enhanced strength of colonic stretch-reflex contraction which reflected the heightened activity of the colonic sensory reflex pathways. The increased value of ΔP/Δt in colonic hypersensitivity indicated a lower threshold of colonic mechanical sensation by which colonic stretch-reflex contraction was elicited by a smaller saline infusion volume during a shorter period of infusion time. Chemogenetic inhibition of primary afferent pathway that was governed by Nav1.8-expressing cells attenuated TNBS-induced up-regulations of AICP, ΔP/Δt, and colonic pain behavior in response to CRD. These findings support that colonometrograms can be used for analysis of colonic pain in mice.
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