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相互作用。最近的数据表明，-异氟烷在脊髓中的作用抑制了对伤害性刺激的运动反应。异氟烷（ISO）和氟烷（HAL），在0.6至0.9 MAC之间，降低在超大伤害性刺激期间和之后发生的运动次数（对运动力的影响较小），并且在0.9至1.1 MAC过渡时，降低运动次数和运动力。然而，中枢神经系统内的特定部位如何参与这些麻醉作用尚不清楚。可能的脊髓和脊髓上的网站包括背角，中央模式发生器，ON-和OFF-细胞的rostralventral延髓（RVM）和大脑皮质。本提案的具体目的是确定1）麻醉对ON/OFF细胞和背角细胞的影响2）去大脑、背外侧索（DLF）损伤和颈髓可逆性冷却阻滞是否通过消除任何下行影响而改变了由超最大刺激引起的运动模式;（3）麻醉对中枢图形发生器的影响。我们假设：1）ON/OFF和背角细胞活性与低浓度ISO和HAL（而非中等浓度ISO和HAL）下的运动相关; 2）DLF病变（通过切断RVM和脊髓背角细胞之间的通信），脊髓冷却（可逆性脊髓化）和丘前去脑将在低ISO和HAL浓度下抑制运动模式; 3）ISO和HAL将在临床相关浓度下破坏中枢模式发生器。了解脑/脊髓与麻醉作用的关系将有助于阐明麻醉的关键终点（健忘症、意识丧失、对伤害性刺激反应不动）之间的关系，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剂。

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.