Effects of sevoflurane and desflurane on the nociceptive responses of substantia gelatinosa neurons in the rat spinal cord dorsal horn: An in vivo patch-clamp analysis

Abstract

Background: 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. Methods: 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). Results: 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. Conclusions: 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.

Volatile versus Total Intravenous Anesthesia for Coronary Artery Bypass Graft Surgery: Analysis of 1586 MYRIAD Trial Patients Managed with the Same Perioperative Protocol

“…This may be attributed to the analgesic effects of sevoflurane. The definite mechanism of this effect is not well defined; nevertheless, this effect has been linked to the suppression of dorsal horn activity mainly via inhibition of excitatory postsynaptic currents in substantia gelatinosa neurons in experimental trials [20]; furthermore, the suppression of the peripheral nervous system activity may also be involved [21,22]. The opioid-sparing effect of VA in cardiac surgery is of special importance.…”

Modeling cortical synaptic effects of anesthesia and their cholinergic reversal

“…At the single cell level, common inhalational anesthetics facilitate inhibitory transmission and suppress excitatory synaptic transmission [ 4 , 5 ] while the extent of effects on specific receptors varies across different anesthetics ( Fig 1 ). Typical inhalational anesthetics such as, isoflurane, sevoflurane and desflurane facilitate inhibitory neurotransmission at GABA A receptors [ 6 , 7 ]. Additionally, depressive modulation of NMDA glutamate receptors has been observed for desflurane and other anesthetic agents [ 8 , 9 ].…”

Multisite Simultaneous Neural Recording of Motor Pathway in Free-Moving Rats

“…Electrophysiological recording of the spinal cord in animal behavior faces more challenges than that of the cortex given the flexible structure of the vertebrae and the softness of the neural tissue. Patch clamp is the most common approach to acquire single neuron signals of spinal cord in vivo [ 32 , 33 , 34 ]. However, the number of channels in this technology is unlikely to be enlarged, and it is difficult to apply it to awake animals.…”