Yao Aubrey, Kim JongBun, Atherley Richard, Jinks Steven L, Carstens Earl, Shargh Sean, Sulger Alana, Antognini Joseph F
Department of Anesthesiology and Pain Medicine, University of California, Davis, CA 95616, USA.
Anesth Analg. 2008 Jun;106(6):1759-64. doi: 10.1213/ane.0b013e3181732ee3.
Gamma-aminobutyric acid type A receptor potentiation and/or N-methyl-d-aspartate (NMDA) receptor inhibition might explain the anesthetic properties of fluorinated aromatic compounds. We hypothesized that depression of dorsal horn neuronal responses to noxious stimulation would correlate with the magnitude of effect of benzene (BNZ), o-difluorobenzene, and hexafluorobenzene (HFB) on NMDA receptors.
Rats were anesthetized with desflurane. A T13-L1 laminectomy allowed extracellular recording of neuronal activity from the lumbar spinal cord. After discontinuing desflurane administration, MAC for each aromatic anesthetic was determined. A 5-s noxious mechanical stimulus was then applied to the hindpaw receptive field of nociceptive dorsal horn neurons, and single-neuron responses were recorded at 0.8 and 1.2 MAC. These responses were also recorded in decerebrate rats receiving BNZ and HFB at 0-1.2 MAC.
In intact rats, depression of responses of dorsal horn neurons to noxious stimulation by peri-MAC increases in BZN, o-difluorobenzene, and HFB correlated directly with their in vitro capacity to block NMDA receptors. In decerebrate rats, 1.2 MAC BNZ depressed nociceptive responses by 60%, with a further percentage decrease continuing from 0.8 to 1.2 MAC approximately equal to that found in intact rats. In decerebrate rats, HFB caused a progressive dose-related decrease in MAC (maximum 25%), but in intact rats, an increase from 0.8 to 1.2 neuronal response caused an (insignificant) increase in neuronal response.
The findings in intact rats suggest that NMDA blockade contributes to the depression of dorsal horn neurons to nociceptive stimulation by fluorinated aromatic anesthetics. These results, combined with the additional findings in decerebrate rats, suggest that supraspinal effects (perhaps on gamma-aminobutyric acid type A receptors) may have a supraspinal facilitatory effect on nociception for HFB.
γ-氨基丁酸A型受体增强和/或N-甲基-D-天冬氨酸(NMDA)受体抑制可能解释了氟化芳香化合物的麻醉特性。我们假设背角神经元对伤害性刺激反应的抑制与苯(BNZ)、邻二氟苯和六氟苯(HFB)对NMDA受体的作用强度相关。
用地氟醚麻醉大鼠。通过T13-L1椎板切除术对腰脊髓神经元活动进行细胞外记录。停止给予地氟醚后,确定每种芳香麻醉剂的最低肺泡有效浓度(MAC)。然后对伤害性背角神经元的后爪感受野施加5秒的伤害性机械刺激,并在0.8和1.2 MAC下记录单神经元反应。在接受0-1.2 MAC的BNZ和HFB的去大脑大鼠中也记录了这些反应。
在完整大鼠中,BNZ、邻二氟苯和HFB在MAC附近增加时,背角神经元对伤害性刺激反应的抑制与它们在体外阻断NMDA受体的能力直接相关。在去大脑大鼠中,1.2 MAC的BNZ使伤害性反应降低60%,从0.8到1.2 MAC进一步降低的百分比与完整大鼠中发现的大致相同。在去大脑大鼠中,HFB导致MAC逐渐剂量相关降低(最大25%),但在完整大鼠中,从0.8到1.2神经元反应增加(不显著)。
完整大鼠的研究结果表明,NMDA阻断有助于氟化芳香麻醉剂使背角神经元对伤害性刺激的抑制。这些结果与去大脑大鼠的其他研究结果相结合,表明脊髓上的作用(可能对γ-氨基丁酸A型受体)可能对HFB的伤害感受有脊髓上的促进作用。