Direct Effect of Remifentanil and Glycine Contained in Ultiva registered on Nociceptive Transmission in the Spinal Cord: In Vivo and Slice Patch Clamp Analyses: e0147339

Background Ultiva registered is commonly administered intravenously for analgesia during general anaesthesia and its main constituent remifentanil is an ultra-short-acting M-opioid receptor agonist. Ultiva registered is not approved for epidural or intrathecal use in clinical practice. Previous studies have reported that Ultiva registered provokes opioid-induced hyperalgesia by interacting with spinal dorsal horn neurons. Ultiva registered contains glycine, an inhibitory neurotransmitter but also an N-methyl-D-aspartate receptor co-activator. The presence of glycine in the formulation of Ultiva registered potentially complicates its effects. We examined how Ultiva registered directly affects nociceptive transmission in the spinal cord. Methods We made patch-clamp recordings from substantia gelatinosa (SG) neurons in the adult rat spinal dorsal horn in vivo and in spinal cord slices. We perfused Ultiva registered onto the SG neurons and analysed its effects on the membrane potentials and synaptic responses activated by noxious mechanical stimuli. Results Bath application of Ultiva registered hyperpolarized membrane potentials under current-clamp conditions and produced an outward current under voltage-clamp conditions. A barrage of excitatory postsynaptic currents (EPSCs) evoked by the stimuli was suppressed by Ultiva registered . Miniature EPSCs (mEPSCs) were depressed in frequency but not amplitude. Ultiva registered -induced outward currents and suppression of mEPSCs were not inhibited by the M-opioid receptor antagonist naloxone, but were inhibited by the glycine receptor antagonist strychnine. The Ultiva registered -induced currents demonstrated a specific equilibrium potential similar to glycine. Conclusions We found that intrathecal administration of Ultiva registered to SG neurons hyperpolarized membrane potentials and depressed presynaptic glutamate release predominantly through the activation of glycine receptors. No Ultiva registered -induced excitatory effects were observed in SG neurons. Our results suggest different analgesic mechanisms of Ultiva registered between intrathecal and intravenous administrations.