TY - JOUR
T1 - Plasticity of cytochrome P450 isozyme expression in rat trigeminal ganglia neurons during inflammation
AU - Ruparel, Shivani
AU - Henry, Michael A.
AU - Akopian, Armen
AU - Patil, Mayur
AU - Zeldin, Darryl C.
AU - Roman, Linda
AU - Hargreaves, Kenneth M.
N1 - Funding Information:
We would like to thank Gabriella Helesic, Mei Li, and Paul Chen for their technical assistance. We would also like to thank Dr. Anibal Diogenes for providing access to his Affymetrix data for selection of the CYPs. We are also grateful to Dr. Amol Patwardhan for his valuable input that he provided for this study, and his preliminary work in this area. The study was supported by the National Institutes of Health (NIH) , R01NS72890 , R01DA019585 , National Center for Research Resources U54RR02438 , and the American Pain Society Pain 2010 Future Leader’s Grant (S.R.). This study was also supported, in part, by the intramural research program of the NIH, National Institute of Environmental Health Sciences ( Z01 ES025034 to D.C.Z.). The University of Texas has claimed intellectual property related to this discovery.
PY - 2012/10
Y1 - 2012/10
N2 - 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.
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.
KW - Cytochrome P450
KW - Sensory neurons
KW - TRPV1
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U2 - 10.1016/j.pain.2012.04.027
DO - 10.1016/j.pain.2012.04.027
M3 - Article
C2 - 22633978
AN - SCOPUS:84866386978
VL - 153
SP - 2031
EP - 2039
JO - Pain
JF - Pain
SN - 0304-3959
IS - 10
ER -