Plasticity of cytochrome P450 isozyme expression in rat trigeminal ganglia neurons during inflammation.

Abstract

Recently, specific oxidized linoleic acid metabolites (OLAMs) have been identified as transient receptor potential vanilloid 1 (TRPV1) channel agonists that contribute to inflammatory and heat hyperalgesia mechanisms, yet the specific mechanism responsible for OLAM synthesis in sensory neurons is unknown. Here, we use molecular, anatomical, calcium imaging, and perforated patch electrophysiology methods to demonstrate the specific involvement of cytochrome P450 enzymes (CYPs) in the oxidation of linoleic acid leading to neuronal activation and show that this is enhanced under inflammatory conditions. Additional studies evaluated CYP expressions in the native rat trigeminal ganglia (TG) tissue and cultures as well as changes in their expression pattern following the induction of peripheral inflammation. Fourteen of 20 candidate transcripts were detected in native TG, and 7 of these displayed altered expression under cultured conditions. Moreover, complete Freund's adjuvant-induced inflammation of vibrissal pad selectively increased expression of CYP3A23/3A1 and CYP2J4 transcripts in TG. In situ hybridization studies demonstrated broad expression pattern of CYP3A23/3A1 and CYP2J4 within TG neurons. Anatomical studies characterized the expression of CYP3A1 and the CYP2J families within TG sensory neurons, including those with TRPV1, with about half of all TRPV1-positive neurons showing more prominent CYP3A1 and CYP2J expression. Together, these findings show that CYP enzymes play a primary role in mediating linoleic acid-evoked activation of sensory neurons and furthermore, implicate the involvement of specific CYPs as contributing to the formation of OLAMs that act as TRPV1 agonists within this subpopulation of nociceptors.

• Authors: Shivani Ruparel, Michael A Henry, Armen Akopian, Mayur Patil, Darryl C Zeldin, Linda Roman, Kenneth M Hargreaves
• Journal: Pain (Pain) Vol. 153 Issue 10 Pg. 2031-2039 (Oct 2012) ISSN: 1872-6623 [Electronic] United States
• PMID: 22633978 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, N.I.H., Intramural)
• Copyright: Copyright © 2012 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.

Chemical References

• Cytochrome P-450 Enzyme System
• Linoleic Acid

Topics

• Animals
• Cytochrome P-450 Enzyme System (metabolism)
• Gene Expression Regulation, Enzymologic
• Hyperalgesia (complications, metabolism)
• Inflammation (etiology, metabolism)
• Linoleic Acid (metabolism)
• Male
• Neuronal Plasticity
• Rats
• Rats, Sprague-Dawley
• Sensory Receptor Cells (metabolism)
• Trigeminal Ganglion (enzymology)