Birder L A, de Groat W C
University of Pittsburgh School of Medicine, Department of Pharmacology, Pennsylvania 15261.
J Neurosci. 1992 Dec;12(12):4878-89. doi: 10.1523/JNEUROSCI.12-12-04878.1992.
This study utilized neuronal c-fos expression to examine the spinal pathways involved in processing nociceptive and non-nociceptive afferent input from the lower urinary tract (LUT) of the urethane-anesthetized rat. C-fos protein was detected immunocytochemically in only a small number of cells (< 2 cells/L6 section) in control animals. However, chemical irritation with 1% acetic acid or mechanical stimulation of the LUT markedly increased the number of c-fos-positive neurons (56-180 cells/L6 section) in four regions of the caudal lumbosacral (L6-S1) spinal cord: medial dorsal horn (MDH), lateral dorsal horn, dorsal commissure (DCM), and sacral parasympathetic nucleus (SPN). Only small numbers of c-fos-positive cells were detected in rostral lumbar segments, a region that is thought to receive nociceptive input from the LUT via afferent pathways in sympathetic nerves. The distribution of c-fos-positive cells in the L6 spinal cord varied according to the stimulus (i.e., urethral catheter, bladder distension, or chemical irritation). Distension of the urinary bladder increased the number of c-fos-positive cells mainly in DCM and SPN regions of the cord. In contrast, irritation of the LUT increased c-fos expression largely in DCM and MDH areas. Spinal cord transection (T8 level) did not alter the c-fos expression induced by a catheter or chemical irritation, indicating that gene expression was mediated by spinal pathways. Denervation experiments showed that c-fos expression was induced by activation of afferent pathways in the pelvic and pudendal nerves. These results suggest that neurons in several regions of the spinal cord are involved in processing afferent input from different parts of the LUT. Neurons in the DCM appear to have an important role since they respond to both nociceptive and non-nociceptive inputs and to visceral (pelvic nerve) and somatic (pudendal nerve) afferent pathways. Thus, these neurons may be involved in the mechanisms of visceral-somatic referred pain.
本研究利用神经元c-fos表达来检测参与处理来自经乌拉坦麻醉大鼠下尿路（LUT）伤害性和非伤害性传入输入的脊髓通路。在对照动物中，仅在少数细胞（<2个细胞/L6节段）中通过免疫细胞化学检测到c-fos蛋白。然而，用1%乙酸进行化学刺激或对LUT进行机械刺激显著增加了尾侧腰骶部（L6-S1）脊髓四个区域中c-fos阳性神经元的数量（56-180个细胞/L6节段）：内侧背角（MDH）、外侧背角、背连合（DCM）和骶副交感核（SPN）。仅在腰段上部检测到少量c-fos阳性细胞，该区域被认为通过交感神经中的传入通路接收来自LUT的伤害性输入。L6脊髓中c-fos阳性细胞的分布因刺激（即尿道插管、膀胱扩张或化学刺激）而异。膀胱扩张主要增加了脊髓DCM和SPN区域中c-fos阳性细胞的数量。相比之下，LUT刺激主要增加了DCM和MDH区域的c-fos表达。脊髓横断（T8水平）并未改变由导管或化学刺激诱导的c-fos表达，表明基因表达是由脊髓通路介导的。去神经实验表明，c-fos表达是由盆神经和阴部神经中传入通路的激活诱导的。这些结果表明，脊髓几个区域的神经元参与处理来自LUT不同部位的传入输入。DCM中的神经元似乎具有重要作用，因为它们对伤害性和非伤害性输入以及内脏（盆神经）和躯体（阴部神经）传入通路均有反应。因此，这些神经元可能参与了内脏-躯体牵涉痛的机制。
