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

Shivani B Ruparel, Michael A. Henry, Armen N Akopian, Mayur Patil, Darryl C. Zeldin, Linda Roman, Kenneth M Hargreaves

Research output: Contribution to journalArticle

23 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)2031-2039
Number of pages9
JournalPain
Volume153
Issue number10
DOIs
StatePublished - Oct 2012

Fingerprint

Trigeminal Ganglion
Linoleic Acid
Cytochrome P-450 Enzyme System
Isoenzymes
Inflammation
Neurons
Sensory Receptor Cells
Nociceptors
Freund's Adjuvant
Electrophysiology
Hyperalgesia
In Situ Hybridization
Hot Temperature
Calcium
vanilloid receptor subtype 1
Enzymes

Keywords

  • Cytochrome P450
  • Sensory neurons
  • TRPV1

ASJC Scopus subject areas

  • Clinical Neurology
  • Anesthesiology and Pain Medicine
  • Neurology
  • Pharmacology

Cite this

Plasticity of cytochrome P450 isozyme expression in rat trigeminal ganglia neurons during inflammation. / Ruparel, Shivani B; Henry, Michael A.; Akopian, Armen N; Patil, Mayur; Zeldin, Darryl C.; Roman, Linda; Hargreaves, Kenneth M.

In: Pain, Vol. 153, No. 10, 10.2012, p. 2031-2039.

Research output: Contribution to journalArticle

Ruparel, Shivani B ; Henry, Michael A. ; Akopian, Armen N ; Patil, Mayur ; Zeldin, Darryl C. ; Roman, Linda ; Hargreaves, Kenneth M. / Plasticity of cytochrome P450 isozyme expression in rat trigeminal ganglia neurons during inflammation. In: Pain. 2012 ; Vol. 153, No. 10. pp. 2031-2039.
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