ANESTHETIC EFFECTS ON SENSORIMOTOR INTEGRATION

我们研究工作的长期目标是阐明脊髓和大脑对麻醉效果的交互作用。最近的数据表明，脊髓中的异氟醚作用抑制了对伤害性刺激的运动反应。异氟醚(ISO)和氟烷(HAL)在0.6到0.9MAC之间，减少了在超最大伤害性刺激期间和之后发生的运动次数(对运动力量影响较小)，在0.9到1.1MAC转变时，减少了运动次数和运动力量。然而，目前尚不清楚中枢神经系统中的特定部位如何参与这些麻醉效果。可能的脊髓和棘上部位包括背角、中央模式生成器、延髓头端腹侧(RVM)和大脑皮层的开和离细胞。这项建议的具体目的是确定1)对开/关细胞和背角细胞的麻醉效应(大动态范围和伤害性特异性)，以及这些效应如何与运动模式相关；2)去大脑、背外侧索损伤和可逆性冷却阻断颈脊髓是否通过消除任何下行影响而改变最大刺激引起的运动模式；3)麻醉对中枢模式生成器的影响。我们假设：1)在低浓度的ISO和HAL下，开/关和背角细胞的活动与运动有关；2)DLF损伤(通过切断RVM和脊髓背角细胞之间的联系)、脊髓降温(可逆棘化)和前丘去大脑将在低ISO和HAL浓度下抑制运动模式；3)在临床相关浓度下，ISO和HAL将扰乱中枢模式生成器。了解脑/脊髓与麻醉作用之间的关系将有助于阐明麻醉的关键终点之间的关系(健忘症、意识丧失、对伤害性刺激的反应不动)，将指导对麻醉机制的进一步研究，并将导致部位特异性麻醉药的产生。

The long term goal of our research efforts is to elucidate the interactive contributions of the spinal cord and brain to anesthetic efficacy. Recent data suggest that -isoflurane action in the spinal cord suppresses movement responses to noxious stimuli. Isoflurane (ISO) and halothane (HAL), between 0.6 and 0.9 MAC, depress the number of movements (with less effect on the force of the movements) that occur during and after supramaximal noxious stimulation, and at the 0.9 to 1.1 MAC transition, decrease the number of movements and the force of the movements. It is unclear, however, how specific sites within the central nervous system participate in these anesthetic effects. Possible spinal and supraspinal sites include the dorsal horn, central pattern generators, ON- and OFF-cells of the rostralventral medulla (RVM) and cerebral cortex. The specific aims of this proposal are to determine 1) anesthetic effects on ON/OFF cells and dorsal horn cells (wide dynamic-range and nociceptive specific), and how these effects correlate with the movement pattern; 2) whether decerebration, dorsolateral funiculus (DLF) lesions and reversible cooling block of the cervical spinal cord alters the movement pattern arising from supramaximal stimulation by eliminating any descending influences; 3) anesthetic effects on central pattern generators. We hypothesize that 1) ON/OFF and dorsal horn cell activity is correlated with movement at low but not moderate ISO and HAL concentrations; 2) DLF lesions (by severing communication between the RVM and spinal dorsal horn cells), spinal cord cooling (reversible spinalization) and pre-collicular decerebration will depress the movement pattern at low ISO and HAL concentrations; 3) ISO and HAL will disrupt central pattern generators at clinically relevant concentrations. Understanding the brain/spinal cord relationship vis-a-vis anesthetic action will aid elucidation of the relationship among critical end-points of anesthesia (amnesia, unconsciousness, immobility in response to noxious stimulation), will guide further research into anesthetic mechanisms, and will lead to site-specific anesthetics.