Department of Anesthesiology, Graduate School of Medicine, Osaka City University, Osaka, Japan.
Mol Pain. 2020 Jan-Dec;16:1744806920903149. doi: 10.1177/1744806920903149.
Volatile anesthetics suppress noxiously evoked activity in the spinal dorsal horn, which could contribute in part to analgesia, immobility. Modulation of excitatory and inhibitory synaptic transmission in substantia gelatinosa neurons could lead to the suppression of dorsal horn activity; however, this phenomenon has not yet been investigated fully.
In urethane-anesthetized rats, extracellular activity of dorsal horn neurons (action potentials) and excitatory/inhibitory postsynaptic currents in substantia gelatinosa neurons were recorded using extracellular and in vivo patch-clamp techniques, respectively, to assess the spontaneous and the noxious-evoked activity. Sevoflurane or desflurane at concentrations ranging from 0.1 to 2 minimum alveolar concentration was administered by inhalation. Hot- and cold-plate tests were performed to assess nociceptive responses during the inhalation of volatile anesthetics at lower anesthetic doses (0.1–0.5 minimum alveolar concentration).
At anesthetic doses (1 and 2 minimum alveolar concentration), both sevoflurane and desflurane decreased the frequency of action potentials in the dorsal horn and the activities of excitatory postsynaptic currents in substantia gelatinosa neurons during pinch stimulation and decreased the activities of spontaneous and miniature excitatory postsynaptic currents. Inhibition of the frequencies was more prominent than that of amplitudes in spontaneous and miniature excitatory postsynaptic currents at these anesthetic doses. However, at subanesthetic doses (0.1 and 0.2 minimum alveolar concentration), desflurane facilitated action potentials and excitatory postsynaptic currents. Inhibitory postsynaptic currents were inhibited by both anesthetics at anesthetic doses (1 and 2 minimum alveolar concentration). Hot- or cold-plate tests showed hyperalgesic effects of desflurane at subanesthetic doses (0.1 and 0.2 minimum alveolar concentration) and a dose-dependent analgesic effect of sevoflurane.
Sevoflurane and desflurane at anesthetic doses suppressed dorsal horn activity mainly via inhibition of excitatory postsynaptic currents in substantia gelatinosa neurons, which would contribute to their analgesic properties. Presynaptic mechanisms were likely in excitatory postsynaptic currents inhibition. Desflurane but not sevoflurane may have a hyperalgesic effect at subanesthetic doses.
挥发性麻醉剂抑制脊髓背角中有害刺激诱发的活动,这可能部分有助于镇痛、运动不能。在胶状质神经元中,兴奋性和抑制性突触传递的调制可能导致背角活动的抑制;然而,这种现象尚未得到充分研究。
在乌拉坦麻醉的大鼠中,使用细胞外和体内膜片钳技术分别记录背角神经元的细胞外活动(动作电位)和胶状质神经元中的兴奋性/抑制性突触后电流,以评估自发性和有害刺激诱发的活动。吸入 0.1 至 2 最低肺泡浓度(MAC)的七氟醚或地氟醚。在较低的麻醉剂量(0.1-0.5 MAC)下吸入挥发性麻醉剂时,通过热板和冷板测试评估伤害性反应。
在麻醉剂量(1 和 2 MAC)下,七氟醚和地氟醚均降低了夹捏刺激时背角中动作电位的频率和胶状质神经元中兴奋性突触后电流的活动,并降低了自发性和微小兴奋性突触后电流的活动。在这些麻醉剂量下,自发性和微小兴奋性突触后电流的频率抑制比幅度抑制更为明显。然而,在亚麻醉剂量(0.1 和 0.2 MAC)下,地氟醚促进了动作电位和兴奋性突触后电流。在麻醉剂量(1 和 2 MAC)下,两种麻醉剂均抑制了抑制性突触后电流。热板或冷板测试显示,在亚麻醉剂量(0.1 和 0.2 MAC)下,地氟醚具有致痛作用,七氟醚具有剂量依赖性的镇痛作用。
在麻醉剂量下,七氟醚和地氟醚通过抑制胶状质神经元中的兴奋性突触后电流抑制背角活动,这有助于它们的镇痛特性。兴奋型突触后电流抑制的可能是突触前机制。地氟醚而非七氟醚在亚麻醉剂量下可能具有致痛作用。