Data from: The control of colonic motility using electrical stimulation to modulate enteric neural circuitry

Electrical stimulation of the enteric nervous system (ENS) is an attractive approach to modify gastrointestinal transit. Colonic motor complexes (CMCs) occur with a periodic rhythm, but the ability to elicit a premature CMC depends, at least in part, upon the intrinsic refractory properties of the ENS, which are presently unknown. The objectives of this study were to record myoelectric complexes (MCs, the electrical correlates of CMCs) in the smooth muscle and (i) determine the refractory periods of MCs, (ii) inform and evaluate closed-loop stimulation to repetitively evoke MCs, and (iii) identify stimulation methods to suppress MC propagation. We dissected the colon from male and female C57BL/6 mice, preserving the integrity of intrinsic circuitry while removing the extrinsic nerves, and measured properties of spontaneous and evoked MCs in vitro. Hexamethonium abolished spontaneous and evoked MCs, confirming the necessary involvement of the ENS for electrically-evoked MCs. Electrical stimulation reduced the mean interval between evoked and spontaneous CMCs (24.6 ± 3.5 vs 70.6 ± 15.7 s, p = 0.0002, n = 7). The absolute refractory period was 4.3 s (95% CI = 2.8 - 5.7 s, R2 = 0.7315, n = 8). Electrical stimulation lead to arrest of fluid distention-evoked propagating MC, and following cessation of stimulation propagation resumed at an increased velocity (n = 9). The timing parameters of electrical stimulation increased the rate of evoked MCs, including the duration of entrained MCs, and provide insights into timing considerations for designing neuromodulation strategies to treat colonic dysmotility.

肠神经系统（enteric nervous system, ENS）的电刺激是调节胃肠道转运的一种颇具前景的方法。结肠运动复合波（colonic motor complexes, CMCs）呈周期性节律发生，但诱发过早CMCs的能力至少部分取决于ENS的内在不应期特性，目前这一特性尚不明确。本研究的目的是记录平滑肌中的肌电复合波（myoelectric complexes, MCs，即CMCs的电生理对应物），并（i）确定MCs的不应期；（ii）为重复诱发MCs的闭环刺激提供依据并进行评估；（iii）确定抑制MCs传播的刺激方法。我们从雄性和雌性C57BL/6小鼠中分离结肠，保留内在神经回路的完整性同时去除外在神经，并在体外测量自发和诱发MCs的特性。六甲铵（hexamethonium）消除了自发和诱发的MCs，证实ENS对于电诱发MCs是必需的。电刺激缩短了诱发与自发CMCs之间的平均间隔（24.6±3.5秒 vs 70.6±15.7秒，p=0.0002，n=7）。绝对不应期为4.3秒（95%置信区间（95% CI）=2.8-5.7秒，R²=0.7315，n=8）。电刺激导致液体扩张诱发的传播性MCs停止，且刺激停止后传播以更快的速度恢复（n=9）。电刺激的时序参数提高了诱发MCs的频率，包括被同步化MCs的持续时间，并为设计治疗结肠动力障碍的神经调节策略时的时序考量提供了见解。