VAGAL MODULATION OF MEDULLARY ON/OFF CELLS

描述：最近的研究表明，电刺激 迷走神经传入影响伤害性感受和可能的痛觉调制神经元(ON 和脱离细胞)以一种与什么相反的方式 将根据当前的开关细胞功能假说进行预测。 因此，本提案的总体目标是履行 电生理研究，更有选择性地表征 迷走神经传入兴奋对On和Off细胞活动的影响 在痛觉减退和痛觉过敏期间。这将会实现的 通过测定5-羟色胺或5-羟色胺受体特异性的作用 产生痛觉减退的剂量的激动剂/拮抗剂以及 脂多糖对ON活性产生痛敏作用的剂量 并在完整和去迷走神经的大鼠中取出细胞。此外，所有研究都将 包括记录自On活动以来的动脉血压 外周血细胞与血压相关，一些研究将包括 腰骶棘丘脑束细胞活动的记录 建立开细胞和离细胞活性与细胞活性之间的关系 脊椎疼痛传递神经元。 这项建议的具体目标是：(1)定量描述 迷走神经输入对对照组ON和OFF细胞的影响及程度 动脉血压与伤害性甩尾的调节 反射，(2)定量表征躯体和内脏的程度 在浅浅和深浅中汇聚到开和关细胞 巴比妥酸盐麻醉状态，以及(3)定量表征 开、关细胞对腰骶棘丘脑束的棘顶效应 迷走神经传入激活过程中的细胞。这些实验将提供 开和关细胞在脊髓顶叶调控中作用的重要信息 伤害性、动脉血压调节和内脏-脏腑的关系 以及内脏-躯体会聚。

DESCRIPTION: Recent investigations showed that electrical stimulation of vagal afferents affects nociception and putative pain modulatory neurons (On and OFF cells) in the rostroventral medulla in a manner opposite to what would be predicted based on the current hypothesis of ON-OFF cell function. The overall objective of the present proposal, therefore, is to perform electrophysiological studies that more selectively characterize the influence of vagal afferent activation on the activity of ON and OFF cells during periods of hypoalgesia and hyperalgesia. This will be accomplished by determining the effects of serotonin or serotonin receptor specific agonists/antagonists at doses that produce hypoalgesia and the effects of lipopolysaccarides at doses that produce hyperalgesia on the activity of ON and OFF cells in intact and vagotomized rats. In addition, all studies will include the recording of arterial blood pressure since the activity of ON and OFF cells is correlated to blood pressure, and some studies will include the recording of activity of lumbosacral spinothalamic tract cells to establish relationship between ON and OFF cell activity with the activity of spinal pain transmission neurons. The specific aims of this proposal are to (1) quantitatively characterize the influence and degree of vagal input to ON and OFF cells in the control of arterial blood pressure and the modulation of the nociceptive tail flick reflex, (2) quantitatively characterize the degree of somatic and visceral convergence to ON and OFF cells in the lightly and deeply barbiturate-anesthetized state, and (3) quantitatively characterize the spinopetal effects of ON and OFF cells on lumbosacral spinothalamic tract cells during activation of vagal afferents. These experiments will provide important information on the role of ON and OFF cells in spinopetal control of nociception, arterial blood pressure regulation, and visceral-visceral and visceral-somatic convergence.