Malykhina A P, Qin C, Greenwood-van Meerveld B, Foreman R D, Lupu F, Akbarali H I
Department of Physiology, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA.
Neurogastroenterol Motil. 2006 Oct;18(10):936-48. doi: 10.1111/j.1365-2982.2006.00807.x.
Clinical studies reveal concomitant occurrence of several gastrointestinal and urologic disorders, including irritable bowel syndrome and interstitial cystitis. The purpose of this study was to determine the mechanisms underlying cross-organ sensitization at the level of dorsal root ganglion (DRG) after acute and subsided gastrointestinal inflammation. DiI (1,1'-dioctadecyl-3,3,3',3'-tetramethylindocarbocyanine perchlorate) and Fast Blue were injected into the distal colon and urinary bladder of male rats, respectively. Convergent DRG neurons were found in L1-L3 and L6-S2 ganglia with an average distribution of 14% +/- 2%. The resting membrane potential (RMP) of cells isolated from upper lumbar (UL) ganglia was -59.8 +/- 2.7 mV, whereas lumbosacral (LS) neurons were more depolarized (RMP = -49.4 +/- 2.1 mV, P < or = 0.05) under control conditions. Acute trinitrobenzene sulfonic acid (TNBS) colitis (3 days) decreased voltage and current thresholds for action potential firing in LS but not UL convergent capsaicin-sensitive neurons. This effect persisted for 30 days in the absence of overt colonic inflammation. The current threshold for action potential (AP) firing in UL cells was also decreased from 165.0 +/- 24.5 pA (control) to 85.0 +/- 19.1 pA at 30 days (P < or = 0.05), indicating increased excitability. The presence of a subpopulation of colon-bladder convergent DRG neurons and their persistent hyperexcitability after colonic inflammation provides a basis for pelvic organ cross-sensitization.
临床研究显示，多种胃肠道和泌尿系统疾病会同时出现，包括肠易激综合征和间质性膀胱炎。本研究的目的是确定急性和消退后的胃肠道炎症后，背根神经节（DRG）水平上跨器官致敏的潜在机制。分别将DiI（1,1'-二辛基-3,3,3',3'-四甲基吲哚羰花青高氯酸盐）和固蓝注入雄性大鼠的远端结肠和膀胱。在L1-L3和L6-S2神经节中发现了汇聚的DRG神经元，平均分布为14%±2%。在对照条件下，从腰上部（UL）神经节分离的细胞的静息膜电位（RMP）为-59.8±2.7 mV，而腰骶部（LS）神经元的去极化程度更高（RMP = -49.4±2.1 mV，P≤0.05）。急性三硝基苯磺酸（TNBS）结肠炎（3天）降低了LS但未降低UL汇聚的辣椒素敏感神经元动作电位发放的电压和电流阈值。在没有明显结肠炎症的情况下，这种效应持续了30天。UL细胞动作电位（AP）发放的电流阈值在30天时也从165.0±24.5 pA（对照）降至85.0±19.1 pA（P≤0.05），表明兴奋性增加。结肠-膀胱汇聚的DRG神经元亚群的存在及其在结肠炎症后的持续高兴奋性为盆腔器官交叉致敏提供了基础。
