Isoflurane prevents nicotine-evoked norepinephrine release from the mouse spinal cord at low clinical concentrations ANESTHESIA AND ANALGESIA Rowley, T. J., Flood, P. 2008; 107 (3): 885-889


Volatile anesthetics inhibit nicotinic acetylcholine receptors at subanesthetic concentrations. In both animal and human studies, similar concentrations of volatile anesthetics have been associated with increased sensitivity to pain. Nicotinic analgesia is thought to involve the enhanced release of norepinephrine. These studies are intended as a "proof of concept" that alteration of the nicotinic facilitation of norepinephrine release is a potential mechanism for isoflurane-induced pronociception.We conducted our study using a murine lumbar spinal cord slice model. We evoked norepinephrine release with nicotine in the presence and absence of isoflurane. To identify the type of nicotinic receptor involved, we studied the effect of receptor and subtype-specific ligands and genetically engineered mice, which lacked the gene expression for the nicotinic beta2 subunit. The amount of [(3)H]-norepinephrine released was measured under the different conditions.Nicotine-facilitated norepinephrine release was significantly and maximally inhibited by isoflurane at concentrations that enhance pain sensitivity in vivo (0.38%). Facilitation of norepinephrine release was mimicked by the alpha 7 selective agonist choline and inhibited in the presence of alpha-bungarotoxin, an alpha 7-nicotinic selective antagonist. Facilitation of norepinephrine release was not different in animals lacking beta2 subunits compared with matched controls.Nicotinic facilitation of norepinephrine release in the spinal cord is inhibited by isoflurane at low clinically relevant concentrations. Because the net effect of noradrenergic tone in the spinal cord is inhibitory, the removal of this mechanism might be responsible for the enhanced pain sensitivity seen at these concentrations of isoflurane.

View details for DOI 10.1213/01.ane.0000287646.85834.1a

View details for Web of Science ID 000258702500029

View details for PubMedID 18713901