Cytochrome P450 Expression in Normal and Painful Human Dental Pulp

Our group has reported that oxidized linoleic acid metabolites (OLAMs) act as transient receptor potential vanilloid 1 (TRPV1) channel agonists and contribute to inflammatory and heat hyperalgesia pain mechanisms.  We have also recently shown that specific cytochrome p450 enzymes (CYPs) contribute to OLAM formation, yet the CYP expression within inflamed human tissues is unknown.   Objectives:   Evaluate the expression of the human equivalent of two CYP isoforms previously identified in rat sensory neurons within normal and inflamed human dental pulp specimens.  Methods: Sections from normal/nonpainful third molars and painful/inflamed molars (n=5/group) were processed with the indirect immunofluorescence method and evaluated with confocal microscopy following staining with antibodies against CYP2J2 and CYP3A4 in combination with antibodies against cell-type specific markers including CD45 (leukocytes), CD68 (macrophages/monocytes), CD31 (endothelial cells) and neurofilament heavy (nerves).  Results: Confocal microscopy showed prominent expression of these CYPs in CD68-positive cells in inflamed specimens, whereas a more variable (low to moderate) expression was seen for these CYPs in leukocytes, endothelial cells and nerve fibers in both normal and inflamed specimens.  Conclusions: The prominent expression of CYPs in specific inflammatory cells suggests that these cells may contribute to the formation of OLAMs, where this formation could contribute to the activation of TRPV1 peripheral nociceptors in the inflamed human dental pulp. These results help identify specific CYPs as potential peripheral targets for the future development of a novel class of analgesics.

Support: NINDS #NS72890/K.Hargreaves, NCRR #UL 1RR025767 and UTHSCSA Dept. of Endodontics