Role of Oxidized Lipids and TRP Channels in Orofacial Pain and Inflammation

Ronald Dubner, Kenneth M Hargreaves, Shivani B Ruparel

Research output: Contribution to journalReview article

14 Scopus citations

Abstract

Acute or chronic inflammation comprises a highly prevalent type of orofacial pain and is mediated by the generation of endogenous agonists that activate numerous receptors expressed on terminals of trigeminal (TG) nociceptive afferent neurons. One such studied receptor is transient receptor potential vanilloid subtype 1 (TRPV1). TRPV1 is a ligand-gated cation channel that is expressed on a major subclass of nociceptors and is found in many orofacial tissues, including dental pulp. Antagonists to TRPV1 reveal an important role for this channel in mediating hypersensitivity in preclinical models of inflammatory or neuropathic pain. Recent studies have demonstrated that endogenous TRPV1 agonists are generated by oxidation of omega-6 polyunsaturated fatty acids, including both linoleic acid and arachidonic acid. A major mechanism triggering the release of oxidative linoleic acid metabolites (OLAMs) and oxidative arachidonic acid metabolites (OAAMs) is the action of oxidative enzymes. Oxidative enzymes such as cytochrome P450 isozymes are rapidly upregulated in TG neurons after orofacial inflammation and increase the capacity of TG neurons to generate OLAMs. Cytochrome P450 isozymes are also increased in immune cells in irreversibly inflamed human dental pulp, and extracts of this tissue have significantly increased capacity to generate OLAMs. Together, these studies point to a novel pain mechanism involving the enzymatic generation of endogenous OLAM and OAAM agonists of TRPV1. This finding provides a rationale for an entirely new class of analgesics by inhibition of oxidative enzyme activity.

Original languageEnglish (US)
Pages (from-to)1117-1123
Number of pages7
JournalJournal of Dental Research
Volume95
Issue number10
DOIs
StatePublished - Sep 1 2016

Keywords

  • arachidonic acid
  • capsaicin
  • cytochrome P450
  • linoleic acid
  • pulpitis
  • TRPV1

ASJC Scopus subject areas

  • Medicine(all)
  • Dentistry(all)

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