Department of Physiology and Biophysics, School of Medicine, Virginia Commonwealth University, Richmond, VA, United States of America.
Department of Internal Medicine, School of Medicine, Virginia Commonwealth University, Richmond, VA, United States of America.
PLoS One. 2021 Mar 12;16(3):e0245410. doi: 10.1371/journal.pone.0245410. eCollection 2021.
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.
本研究提出了一种非手术方法，通过结肠测量术来评估小鼠的结肠机械敏感性，该技术通过在恒速向远端结肠输注盐水时记录腔内压力来测量结肠牵张反射收缩。结肠测量术已被用于评估健康个体和神经障碍患者的结肠功能。在这里，我们发现结肠测量术也可以在小鼠中实施，最佳的盐水输注率为 1.2 mL/h。结肠测量图显示间歇性的压力升高，这是由周期性的结肠收缩引起的。在 2,4,6-三硝基苯磺酸（TNBS）诱导的结肠炎症后、原发性传入神经元的化学遗传激活后或结直肠扩张（CRD）立即刺激结肠后引起的结肠高敏性场景中，腔内压力的幅度（AICP）显著升高，伴随着更快的压力上升（ΔP/Δt）。与结肠高敏相关的 AICP 升高是结肠牵张反射收缩强度增强的结果，反映了结肠感觉反射途径的活性增强。结肠高敏性中ΔP/Δt 的增加表明结肠机械感觉的阈值降低，通过在较短的输注时间内输注较小的盐水体积，可以引起结肠牵张反射收缩。由表达 Nav1.8 的细胞支配的初级传入途径的化学遗传抑制减弱了 TNBS 诱导的 AICP、ΔP/Δt 和 CRD 引起的结肠疼痛行为的上调。这些发现支持结肠测量图可用于分析小鼠的结肠疼痛。
