Baez Madelyn A, Brink Thaddeus S, Mason Peggy
Committee on Neurobiology and Department of Neurobiology, Pharmacology, and Physiology, University of Chicago, Chicago, Illinois 60637, USA.
J Neurosci. 2005 Jan 12;25(2):384-94. doi: 10.1523/JNEUROSCI.3536-04.2005.
We studied how the nervous system selects between noxious stimulus-evoked withdrawals and micturition, movements that are necessary for survival but use overlapping muscles and therefore cannot occur simultaneously. In lightly anesthetized rats, micturition was favored, because noxious stimulation never interrupted micturition, whereas withdrawals were suppressed during voiding. Neurons in the ventromedial medulla (VMM) are a major source of descending antinociceptive signals. To test whether VMM neurons support withdrawal suppression during micturition, the discharge of VMM neurons was recorded during continence and micturition. VMM cells that were inhibited (M-inh) or excited (M-exc) during micturition were observed. M-inh cells were excited by noxious cutaneous stimulation and thus are likely nociception facilitating, whereas M-exc cells were inhibited by noxious heat and are likely nociception inhibiting. The excitation of nociception-inhibiting M-exc and inhibition of nociception-facilitating M-inh cells predicts suppression of withdrawals during micturition. M-exc cells were typically silent before micturition, whereas most M-inh cells fired before micturition, suggesting that these cells may also play a preparatory role for micturition. To test this idea, we examined manipulations that either advanced or delayed the onset of micturition. Hypothalamic stimulation and noxious paw heat advanced micturition while exciting M-inh cells and inhibiting M-exc cells. In contrast, colorectal distension, a stimulus that delays micturition, inhibited M-inh cells and excited M-exc cells. These results suggest a model in which, during continence, VMM M-inh cells facilitate and M-exc cells inhibit bladder afferents, advancing micturition onset when M-inh cells are activated and delaying onset when M-exc cells are activated.
我们研究了神经系统如何在有害刺激诱发的退缩反应和排尿之间进行选择,这两种行为对生存至关重要,但使用重叠的肌肉,因此不能同时发生。在轻度麻醉的大鼠中,排尿更受青睐,因为有害刺激从未中断排尿,而在排尿时退缩反应受到抑制。延髓腹内侧(VMM)的神经元是下行抗伤害信号的主要来源。为了测试VMM神经元是否在排尿期间支持退缩反应的抑制,在大鼠节制排尿和排尿期间记录了VMM神经元的放电情况。观察到在排尿期间被抑制(M-inh)或兴奋(M-exc)的VMM细胞。M-inh细胞受到有害皮肤刺激的兴奋,因此可能促进伤害感受,而M-exc细胞受到有害热刺激的抑制,可能抑制伤害感受。抑制伤害感受的M-exc细胞的兴奋和促进伤害感受的M-inh细胞的抑制预示着排尿期间退缩反应的抑制。M-exc细胞在排尿前通常处于静息状态,而大多数M-inh细胞在排尿前放电,这表明这些细胞可能也在排尿中起准备作用。为了验证这一想法,我们研究了提前或延迟排尿开始的操作。下丘脑刺激和有害的爪部热刺激提前了排尿时间,同时兴奋了M-inh细胞并抑制了M-exc细胞。相反,结直肠扩张这种延迟排尿的刺激抑制了M-inh细胞并兴奋了M-exc细胞。这些结果提示了一种模型,即在节制排尿期间,VMM的M-inh细胞促进而M-exc细胞抑制膀胱传入神经,当M-inh细胞被激活时提前排尿开始时间,当M-exc细胞被激活时延迟排尿开始时间。