TY  - JOUR
A1  - Rittner, Heike Lydia
A1  - Hackel, Dagmar
A1  - Pflücke, Diana
A1  - Neumann, Annick
A1  - Viebahn, Johannes
A1  - Mousa, Shaaban
A1  - Wischmeyer, Erhard
A1  - Roewer, Norbert
A1  - Brack, Alexander
T1  - The Connection of Monocytes and Reactive Oxygen Species in Pain
JF  - PLoS ONE
N2  - The interplay of specific leukocyte subpopulations, resident cells and proalgesic mediators results in pain in inflammation. Proalgesic mediators like reactive oxygen species (ROS) and downstream products elicit pain by stimulation of transient receptor potential (TRP) channels. The contribution of leukocyte subpopulations however is less clear. Local injection of neutrophilic chemokines elicits neutrophil recruitment but no hyperalgesia in rats. In meta-analyses the monocytic chemoattractant, CCL2 (monocyte chemoattractant protein-1; MCP-1), was identified as an important factor in the pathophysiology of human and animal pain. In this study, intraplantar injection of CCL2 elicited thermal and mechanical pain in Wistar but not in Dark Agouti (DA) rats, which lack p47phox, a part of the NADPH oxidase complex. Inflammatory hyperalgesia after complete Freund's adjuvant (CFA) as well as capsaicin-induced hyperalgesia and capsaicin-induced current flow in dorsal root ganglion neurons in DA were comparable to Wistar rats. Macrophages from DA expressed lower levels of CCR2 and thereby migrated less towards CCL2 and formed limited amounts of ROS in vitro and 4-hydroxynonenal (4-HNE) in the tissue in response to CCL2 compared to Wistar rats. Local adoptive transfer of peritoneal macrophages from Wistar but not from DA rats reconstituted CCL2-triggered hyperalgesia in leukocyte-depleted DA and Wistar rats. A pharmacological stimulator of ROS production (phytol) restored CCL2-induced hyperalgesia in vivo in DA rats. In Wistar rats, CCL2-induced hyperalgesia was completely blocked by superoxide dismutase (SOD), catalase or tempol. Likewise, inhibition of NADPH oxidase by apocynin reduced CCL2-elicited hyperalgesia but not CFA-induced inflammatory hyperalgesia. In summary, we provide a link between CCL2, CCR2 expression on macrophages, NADPH oxidase, ROS and the development CCL2-triggered hyperalgesia, which is different from CFA-induced hyperalgesia. The study further supports the impact of CCL2 and ROS as potential targets in pain therapy.
KW  - analysis of variance
KW  - chemokines
KW  - hyperalgesia
KW  - inflammation
KW  - macrophages
KW  - monocytes
KW  - white blood cells
KW  - wistar rats
Y1  - 2013
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-96669
ER  - 
TY  - THES
A1  - Partheil, Anna
T1  - Monozyten und Prostaglandine in der Schmerzentstehung
T1  - Monocytes and prostaglandins in the development of inflammatory pain
N2  - Schmerz ist eine klassische Komponente von Entzündungsreaktionen. Im Rahmen des Entzündungsgeschehens werden Zytokine und Chemokine freigesetzt, die Leukozyten zum Entzündungsort rekrutieren.  Über die Freisetzung weiterer proalgetischer Mediatoren tragen diese zur Aktivierung und Sensitivierung von Nozizeptoren und damit zur Schmerzentstehung bei. Das Monozyten-rekrutierende Chemokin CCL2 verursachte in Verhaltensexperimenten eine Hyperalgesie bei Ratten. Die Hyperalgesie war durch den Cox-2 Inhibitor Parecoxib vollständig reversibel. Daher wurde in dieser Arbeit  die Rolle von Monozyten und Prostaglandinen in der Entstehung dieser Hyperalgesie untersucht. Dazu wurde in vitro die Cox-2 Expression und die Prostaglandin-Bildung in humanen Monozyten und Peritonealmakrophagen der Ratte nach CCL2 Stimulation bestimmt. Zudem wurde in vivo die Cox-2 Expression im Rückenmark und in der Rattenpfote nach CCL2 Injektion in die Pfote untersucht.
N2  - One of the main components of inflammation is pain. In inflammation cytokines and chemokines are secreted and recruit leukocytes to the site of inflammation. Leukocytes release proalgesic mediators that activate and sensitize nociceptors and cause pain. Behavioral tests showed that the chemokine CCL2 (monocyte recruiting protein 2) causes hyperalgesia in rats. This hyperalgesia was blocked by parecoxib, a Cox-2 inhibitor. To further investigate the role of monocytes and prostaglandins in the development of hyperalgesia, Cox-2 expression and prostaglandin production were determined in vitro after stimulation of human monocytes and rat peritoneal macrophages with CCL2. In vivo, Cox-2 expression in spinal cord and paw tissue of rats was examined after injection of CCL2 into the paw.
KW  - Schmerz
KW  - CCL2
KW  - pain
KW  - Entzündung
KW  - Monozyten
KW  - Prostaglandine
KW  - inflammation
KW  - monocytes
KW  - prostaglandins
Y1  - 2013
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-85091
ER  -