S that sensitize and activate peripheral nociceptors resulting in an afferent
S that sensitize and activate peripheral nociceptors resulting in an afferent barrage to dorsal horn neurons. The transient receptor potential vanilloid subtype-1 (TRPV1) receptor is a ligand-gated PubMed ID:http://www.ncbi.nlm.nih.gov/pubmed/27107493 cation channel that is expressed on certain nociceptors, is activated by noxious stimuli such as heat, and mediates inflammatory heat hyperalgesia [1,2]. During tissue inflammation, TRPV1 activity is modulated by several classes of* Correspondence: [email protected] 1 Department of Endodontics, University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Drive, San Antonio, TX 78229, USA 2 Department of Physiology, University of Texas Health Science Center at San Antonio, San Antonio, TX, USAmediators such as arachidonic acid metabolites, bradykinin, nerve growth factor (NGF), as well as prostaglandins [3-5]. One class of endogenous mediators that activate TRPV1 consists of oxidized linoleic acid metabolites (OLAMs), namely, 9-and 13-hydroxy-10E,12Z-octadecadienoic acid (9-HODE and 13-HODE) as well their metabolites, 9-oxoODE and 13-oxoODE. Previous studies have reported that the OLAMs are synthesized under inflammatory conditions such as atherosclerosis and rheumatoid arthritis [6-8] as well as shown to be increased in serum of patients with chronic pancreatitis [9]. In addition, several groups have detected OLAMs in endothelial cells, macrophages and neutrophils [10,11], cell types activated during tissue inflammation. However,?2012 Ruparel et al.; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.Ruparel et al. Molecular Pain 2012, 8:73 http://www.molecularpain.com/content/8/1/Page 2 ofonly recently have OLAMs been demonstrated to activate TRPV1 in both peripheral tissues and Pemafibrate solubility spinal dorsal horn [12,13]. Importantly, there is a gap in knowledge of this system since it is not known whether OLAMs contribute to activation of peripheral TRPV1 during tissue inflammation. In the current study, we investigated the peripheral action of OLAMs in the rat complete Freund’s adjuvant (CFA) model of inflammation. Previously, we have shown that CYP inhibtors block linoleic acid activation of TRPV1 in cultured sensory neurons [14], suggesting that CYP isozymes mediate the formation of TRPV1active linoleic acid metabolites. Accordingly, we conducted parallel in vitro and in vivo studies to determine whether peripheral CYPs in inflamed tissue mediate OLAM activation of TRPV1.Jose, CA, USA) and grown in the presence of 10 FBS and 100 ng/mL NGF (Harlan, Indianapolis, IN, USA) as described previously [15]. For determination of CGRP release, TGs from three rats were cultured as described [16] and plated on 24-well poly-d-lysine-coated plate yielding 8000 cells per well. The media were replaced at the end of 24 h and then 48 h later. All the experiments were PubMed ID:https://www.ncbi.nlm.nih.gov/pubmed/26778282 performed on day 5 of the neuronal cultures.Calcium imagingMethodsAnimalsAll protocols were approved by the Institutional Animal Care and Use Committee of the University of Texas Health Science Center at San Antonio. Male Sprague?Dawley rats (Charles River Laboratories, Inc., Wilmington, MA, USA) were used for all the studies except in one experiment where wild-type and TRPV1 knockout C57BL/6 mice (Jackson Laboratories) were used. Animals were.
