PMID- 22633978 OWN - NLM STAT- MEDLINE DCOM- 20130306 LR - 20211021 IS - 1872-6623 (Electronic) IS - 0304-3959 (Print) IS - 0304-3959 (Linking) VI - 153 IP - 10 DP - 2012 Oct TI - Plasticity of cytochrome P450 isozyme expression in rat trigeminal ganglia neurons during inflammation. PG - 2031-2039 LID - 10.1016/j.pain.2012.04.027 [doi] AB - 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. CI - Copyright (c) 2012 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved. FAU - Ruparel, Shivani AU - Ruparel S AD - Department of Endodontics, University of Texas Health Science Center at San Antonio, San Antonio, TX, USA Division of Intramural Research, National Institute of Environmental Health Science (NIEHS), National Institutes of Health, Research Triangle Park, NC, USA Department of Biochemistry, University of Texas Health Science Center at San Antonio, San Antonio, TX, USA. FAU - Henry, Michael A AU - Henry MA FAU - Akopian, Armen AU - Akopian A FAU - Patil, Mayur AU - Patil M FAU - Zeldin, Darryl C AU - Zeldin DC FAU - Roman, Linda AU - Roman L FAU - Hargreaves, Kenneth M AU - Hargreaves KM LA - eng GR - R01DA019585/DA/NIDA NIH HHS/United States GR - Z01 ES025034/Intramural NIH HHS/United States GR - UL1 TR000149/TR/NCATS NIH HHS/United States GR - UL1 TR001120/TR/NCATS NIH HHS/United States GR - R01 DA019585/DA/NIDA NIH HHS/United States GR - R01 NS072890/NS/NINDS NIH HHS/United States GR - R01NS72890/NS/NINDS NIH HHS/United States GR - UL1 RR025767/RR/NCRR NIH HHS/United States GR - U54RR02438/RR/NCRR NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, N.I.H., Intramural DEP - 20120526 PL - United States TA - Pain JT - Pain JID - 7508686 RN - 9035-51-2 (Cytochrome P-450 Enzyme System) RN - 9KJL21T0QJ (Linoleic Acid) SB - IM CIN - Pain. 2012 Oct;153(10):1987-8. PMID: 22681878 MH - Animals MH - Cytochrome P-450 Enzyme System/*metabolism MH - Gene Expression Regulation, Enzymologic MH - Hyperalgesia/complications/*metabolism MH - Inflammation/etiology/*metabolism MH - Linoleic Acid/*metabolism MH - Male MH - *Neuronal Plasticity MH - Rats MH - Rats, Sprague-Dawley MH - Sensory Receptor Cells/*metabolism MH - Trigeminal Ganglion/*enzymology PMC - PMC3430817 MID - NIHMS374509 COIS- The authors have declared that no other conflict of interest exists. EDAT- 2012/05/29 06:00 MHDA- 2013/03/07 06:00 PMCR- 2013/10/01 CRDT- 2012/05/29 06:00 PHST- 2012/02/09 00:00 [received] PHST- 2012/04/25 00:00 [revised] PHST- 2012/04/26 00:00 [accepted] PHST- 2012/05/29 06:00 [entrez] PHST- 2012/05/29 06:00 [pubmed] PHST- 2013/03/07 06:00 [medline] PHST- 2013/10/01 00:00 [pmc-release] AID - 00006396-201210000-00010 [pii] AID - 10.1016/j.pain.2012.04.027 [doi] PST - ppublish SO - Pain. 2012 Oct;153(10):2031-2039. doi: 10.1016/j.pain.2012.04.027. Epub 2012 May 26.