title: Resolvin E1 Inhibits Substance P-Induced Potentiation of TRPV1 in Primary Sensory Neurons.
abstract: The neuropeptide substance P (SP) is expressed in primary sensory neurons and is commonly regarded as a "pain" neurotransmitter. Upon peripheral inflammation, SP activates the neurokinin-1 (NK-1) receptor and potentiates activity of transient receptor potential vanilloid subtype 1 (TRPV1), which is coexpressed by nociceptive neurons. Therefore, SP functions as an important neurotransmitter involved in the hypersensitization of inflammatory pain. Resolvin E1 (RvE1), derived from omega-3 polyunsaturated fatty acids, inhibits TRPV1 activity via activation of the chemerin 23 receptor (ChemR23)-an RvE1 receptor located in dorsal root ganglion neurons-and therefore exerts an inhibitory effect on inflammatory pain. We demonstrate here that RvE1 regulates the SP-induced potentiation of TRPV1 via G-protein coupled receptor (GPCR) on peripheral nociceptive neurons. SP-induced potentiation of TRPV1 inhibited by RvE1 was blocked by the Gαi-coupled GPCR inhibitor pertussis toxin and the G-protein inhibitor GDPβ-S. These results indicate that a low concentration of RvE1 strongly inhibits the potentiation of TRPV1, induced by the SP-mediated activation of NK-1, via a GPCR signaling pathway activated by ChemR23 in nociceptive neurons. RvE1 might represent a new therapeutic target for the treatment of inflammatory pain as a prospective endogenous inhibitor that strongly inhibits TRPV1 activity associated with peripheral inflammation.
authors.affiliation: Department of Anesthesiology and Pain Medicine, Gachon University, Gil Medical Center, Incheon 21565, Republic of Korea.
authors.forename: Youn Yi
authors.initials: YY
authors.lastname: Jo
authors.affiliation: Department of Anesthesiology and Pain Medicine, Gachon University, Gil Medical Center, Incheon 21565, Republic of Korea.
authors.forename: Ji Yeon
authors.initials: JY
authors.lastname: Lee
authors.affiliation: Department of Physiology, College of Medicine, Gachon University, Incheon 21999, Republic of Korea.
authors.forename: Chul-Kyu
authors.identifier: 0000-0002-4152-3022
authors.initials: CK
authors.lastname: Park
mesh_terms: D000818:Animals; D000950:Antigens, Ly / Q000378:metabolism; D002478:Cells, Cultured; D015118:Eicosapentaenoic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D005727:Ganglia, Spinal / Q000187:drug effects* / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D055651:NK Cell Lectin-Like Receptor Subfamily B / Q000378:metabolism; D018408:Patch-Clamp Techniques; D019707:Receptors, Chemokine; D043562:Receptors, G-Protein-Coupled; D020133:Reverse Transcriptase Polymerase Chain Reaction; D011984:Sensory Receptor Cells / Q000187:drug effects* / Q000378:metabolism*; D013373:Substance P / Q000378:metabolism* / Q000494:pharmacology*; D050916:TRPV Cation Channels / Q000378:metabolism*
chemical_list: D000950:Antigens, Ly; C486456:CMKLR1 protein, mouse; C527211:Klrb1c protein, mouse; D055651:NK Cell Lectin-Like Receptor Subfamily B; D019707:Receptors, Chemokine; D043562:Receptors, G-Protein-Coupled; D050916:TRPV Cation Channels; C493921:TRPV1 protein, mouse; D013373:Substance P; D015118:Eicosapentaenoic Acid; C499823:5S,12R,18R-trihydroxy-6Z,8E,10E,14Z,16E-eicosapentaenoic acid