Isoflurane prevents nicotine-evoked norepinephrine release from the mouse spinal cord at low clinical concentrations

Anesthesia and Analgesia
Thomas J Rowley, Pamela Flood

Abstract

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 ...Continue Reading

References

Jan 1, 1997·Advances in Pharmacology·L M Colquhoun, J W Patrick
Jun 25, 2002·European Journal of Pharmacology·Caterina VirginioGeorg C Terstappen
Jul 20, 2002·Anesthesiology·Pamela FloodKristen M Coates
Aug 10, 2002·Anesthesiology·Xinhui Li, James C Eisenach
Mar 23, 2005·Anesthesia and Analgesia·Thomas J RowleyPamela Flood
Apr 22, 2006·Brain : a Journal of Neurology·Laura L Boles Ponto

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Citations

Oct 5, 2011·Psychological Bulletin·Joseph W DitreMary M Meagher
Feb 4, 2010·The Journal of Pharmacology and Experimental Therapeutics·Keith L Shelton
Jun 12, 2009·Journal of Neurophysiology·Bruce E HerringAaron P Fox
Aug 21, 2008·Anesthesia and Analgesia·Neal L Benowitz
Aug 21, 2008·Anesthesia and Analgesia·Thomas J RowleyPamela Flood

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