title: Nox2-dependent signaling between macrophages and sensory neurons contributes to neuropathic pain hypersensitivity.
abstract: Emerging lines of evidence indicate that production of reactive oxygen species (ROS) at distinct sites of the nociceptive system contributes to the processing of neuropathic pain. However, the mechanisms underlying ROS production during neuropathic pain processing are not fully understood. We here detected the ROS-generating nicotinamide adenine dinucleotide phosphate oxidase isoform Nox2 in macrophages of dorsal root ganglia (DRG) in mice. In response to peripheral nerve injury, Nox2-positive macrophages were recruited to DRG, and ROS production was increased in a Nox2-dependent manner. Nox2-deficient mice displayed reduced neuropathic pain behavior after peripheral nerve injury, whereas their immediate responses to noxious stimuli were normal. Moreover, injury-induced upregulation of tumor necrosis factor α was absent, and activating transcription factor 3 induction was reduced in DRG of Nox2-deficient mice, suggesting an attenuated macrophage-neuron signaling. These data suggest that Nox2-dependent ROS production in macrophages recruited to DRG contributes to neuropathic pain hypersensitivity, underlining the observation that Nox-derived ROS exert specific functions during the processing of pain.
authors.affiliation: Pharmazentrum Frankfurt/ZAFES, Institute of Clinical Pharmacology, Goethe University Medical School, Frankfurt am Main, Germany.
authors.forename: Wiebke
authors.initials: W
authors.lastname: Kallenborn-Gerhardt
authors.affiliation: Pharmazentrum Frankfurt/ZAFES, Institute of Clinical Pharmacology, Goethe University Medical School, Frankfurt am Main, Germany.
authors.forename: Stephan W
authors.initials: SW
authors.lastname: Hohmann
authors.affiliation: Pharmazentrum Frankfurt/ZAFES, Institute of Clinical Pharmacology, Goethe University Medical School, Frankfurt am Main, Germany.
authors.forename: Katharina M J
authors.initials: KM
authors.lastname: Syhr
authors.affiliation: Institute of Cardiovascular Physiology, Goethe University Medical School, Frankfurt am Main, Germany.
authors.forename: Katrin
authors.initials: K
authors.lastname: Schröder
authors.affiliation: Pharmazentrum Frankfurt/ZAFES, Institute of Clinical Pharmacology, Goethe University Medical School, Frankfurt am Main, Germany.
authors.forename: Marco
authors.initials: M
authors.lastname: Sisignano
authors.affiliation: Institute of Biochemistry I/ZAFES, Goethe University Frankfurt, Frankfurt am Main, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Weigert
authors.affiliation: Pharmazentrum Frankfurt/ZAFES, Institute of Clinical Pharmacology, Goethe University Medical School, Frankfurt am Main, Germany.
authors.forename: Jana E
authors.initials: JE
authors.lastname: Lorenz
authors.affiliation: Pharmazentrum Frankfurt/ZAFES, Institute of Clinical Pharmacology, Goethe University Medical School, Frankfurt am Main, Germany; Institute of Pharmacology and Toxicology, ZBAF, Witten/Herdecke University, Witten, Germany.
authors.forename: Ruirui
authors.initials: R
authors.lastname: Lu
authors.affiliation: Institute of Biochemistry I/ZAFES, Goethe University Frankfurt, Frankfurt am Main, Germany.
authors.forename: Bernhard
authors.initials: B
authors.lastname: Brüne
authors.affiliation: Institute of Cardiovascular Physiology, Goethe University Medical School, Frankfurt am Main, Germany.
authors.forename: Ralf P
authors.initials: RP
authors.lastname: Brandes
authors.affiliation: Pharmazentrum Frankfurt/ZAFES, Institute of Clinical Pharmacology, Goethe University Medical School, Frankfurt am Main, Germany; Fraunhofer Institute for Molecular Biology and Applied Ecology - Project Group Translational Medicine and Pharmacology (IME-TMP), Frankfurt am Main, Germany.
authors.forename: Gerd
authors.initials: G
authors.lastname: Geisslinger
authors.affiliation: Pharmazentrum Frankfurt/ZAFES, Institute of Clinical Pharmacology, Goethe University Medical School, Frankfurt am Main, Germany; Institute of Pharmacology and Toxicology, ZBAF, Witten/Herdecke University, Witten, Germany. Electronic address: Achim.Schmidtko@uni-wh.de.
authors.forename: Achim
authors.initials: A
authors.lastname: Schmidtko
mesh_terms: D000818:Animals; D002450:Cell Communication / Q000502:physiology*; D005727:Ganglia, Spinal / Q000378:metabolism; D006930:Hyperalgesia / Q000209:etiology / Q000378:metabolism*; D008264:Macrophages / Q000378:metabolism*; D008562:Membrane Glycoproteins / Q000378:metabolism*; D051379:Mice; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases / Q000378:metabolism*; D009437:Neuralgia / Q000209:etiology / Q000378:metabolism*; D059348:Peripheral Nerve Injuries / Q000150:complications / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D011984:Sensory Receptor Cells / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology
chemical_list: D008562:Membrane Glycoproteins; D017382:Reactive Oxygen Species; C488842:Cybb protein, mouse; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases
keywords: Dorsal root ganglion; Knockout mice; Neuropathic pain; Peripheral nerve injury; Reactive oxygen species