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Peroxynitrite affects lidocaine by acting on membrane-constituting lipids
Takahiro Ueno1, Maki Mizogami, Ko Takakura
1Department of Anesthesiology, Asahi University School of Dentistry, Gifu, Japan.
Journal of Anesthesia
|November 18, 2008
Summary
Inflammation reduces local anesthetic effectiveness. Inflammatory peroxynitrite rigidifies nerve cell membranes, decreasing lidocaine
Area of Science:
- Biochemistry
- Pharmacology
- Neuroscience
Background:
- Inflammation, particularly in dental conditions like pulpitis and periodontitis, often diminishes local anesthetic efficacy.
- Local anesthetic action is linked to their interaction with lipid bilayers, influencing membrane properties like fluidity.
- Peroxynitrite, a product of inflammatory cells, is implicated in altering nerve cell membranes and anesthetic effectiveness.
Purpose of the Study:
- To investigate if peroxynitrite affects membrane lipids, thereby reducing the membrane interaction of lidocaine.
- To understand the role of peroxynitrite in the failure of local anesthetics during inflammation.
Main Methods:
- Liposomes composed of various phospholipids were used to model nerve cell membranes.
- Fluorescence polarization measured changes in membrane fluidity after peroxynitrite treatment.
- The effect of peroxynitrite on lidocaine's membrane-fluidizing capacity was assessed.
Main Results:
- Peroxynitrite (0.1-50 microM) rigidified membranes made of unsaturated phospholipids and specific phosphatidylcholines (DOPC, SAPC).
- Peroxynitrite did not affect the fluidity of membranes composed of dipalmitoylphosphatidylcholine (DPPC).
- Pre-treatment with peroxynitrite reduced lidocaine's fluidizing effect on membranes by 14-37%.
Conclusions:
- Inflammatory peroxynitrite may impair local anesthesia by altering membrane-constituting unsaturated phospholipids.
- This mechanism contributes to the observed decrease in local anesthetic effectiveness in inflamed tissues.
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