title: Slack channels expressed in sensory neurons control neuropathic pain in mice.
abstract: Slack (Slo2.2) is a sodium-activated potassium channel that regulates neuronal firing activities and patterns. Previous studies identified Slack in sensory neurons, but its contribution to acute and chronic pain in vivo remains elusive. Here we generated global and sensory neuron-specific Slack mutant mice and analyzed their behavior in various animal models of pain. Global ablation of Slack led to increased hypersensitivity in models of neuropathic pain, whereas the behavior in models of inflammatory and acute nociceptive pain was normal. Neuropathic pain behaviors were also exaggerated after ablation of Slack selectively in sensory neurons. Notably, the Slack opener loxapine ameliorated persisting neuropathic pain behaviors. In conclusion, Slack selectively controls the sensory input in neuropathic pain states, suggesting that modulating its activity might represent a novel strategy for management of neuropathic pain.
authors.affiliation: Institut für Pharmakologie und Toxikologie, Universität Witten/Herdecke, Zentrum für Biomedizinische Ausbildung und Forschung, 58453 Witten, Germany, Pharmazentrum Frankfurt/Zentrum für Arzneimittelforschung, Entwicklung und Sicherheit, Institut für Klinische Pharmakologie, Universitätsklinikum Frankfurt, 60590 Frankfurt am Main, Germany.
authors.forename: Ruirui
authors.initials: R
authors.lastname: Lu
authors.affiliation: Pharmakologie, Toxikologie und Klinische Pharmazie, Institut für Pharmazie, 72076 Tübingen, Germany.
authors.forename: Anne E
authors.initials: AE
authors.lastname: Bausch
authors.affiliation: Pharmazentrum Frankfurt/Zentrum für Arzneimittelforschung, Entwicklung und Sicherheit, Institut für Klinische Pharmakologie, Universitätsklinikum Frankfurt, 60590 Frankfurt am Main, Germany.
authors.forename: Wiebke
authors.initials: W
authors.lastname: Kallenborn-Gerhardt
authors.affiliation: Klinik für Anästhesiologie und Intensivmedizin, Medizinische Hochschule Hannover, 30625 Hannover, Germany, and.
authors.forename: Carsten
authors.initials: C
authors.lastname: Stoetzer
authors.affiliation: Fraunhofer Institute for Molecular Biology and Applied Ecology IME, 60590 Frankfurt am Main, Germany.
authors.forename: Natasja
authors.initials: N
authors.lastname: Debruin
authors.affiliation: Pharmakologie, Toxikologie und Klinische Pharmazie, Institut für Pharmazie, 72076 Tübingen, Germany.
authors.forename: Peter
authors.initials: P
authors.lastname: Ruth
authors.affiliation: Pharmazentrum Frankfurt/Zentrum für Arzneimittelforschung, Entwicklung und Sicherheit, Institut für Klinische Pharmakologie, Universitätsklinikum Frankfurt, 60590 Frankfurt am Main, Germany, Fraunhofer Institute for Molecular Biology and Applied Ecology IME, 60590 Frankfurt am Main, Germany.
authors.forename: Gerd
authors.initials: G
authors.lastname: Geisslinger
authors.affiliation: Klinik für Anästhesiologie und Intensivmedizin, Medizinische Hochschule Hannover, 30625 Hannover, Germany, and.
authors.forename: Andreas
authors.initials: A
authors.lastname: Leffler
authors.affiliation: Pharmakologie, Toxikologie und Klinische Pharmazie, Institut für Pharmazie, 72076 Tübingen, Germany, achim.schmidtko@uni-wh.de robert.lukowski@uni-tuebingen.de.
authors.forename: Robert
authors.initials: R
authors.lastname: Lukowski
authors.affiliation: Institut für Pharmakologie und Toxikologie, Universität Witten/Herdecke, Zentrum für Biomedizinische Ausbildung und Forschung, 58453 Witten, Germany, Pharmazentrum Frankfurt/Zentrum für Arzneimittelforschung, Entwicklung und Sicherheit, Institut für Klinische Pharmakologie, Universitätsklinikum Frankfurt, 60590 Frankfurt am Main, Germany, achim.schmidtko@uni-wh.de robert.lukowski@uni-tuebingen.de.
authors.forename: Achim
authors.initials: A
authors.lastname: Schmidtko
mesh_terms: D000818:Animals; D006358:Hot Temperature; D006930:Hyperalgesia / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D051379:Mice; D018345:Mice, Knockout; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D009437:Neuralgia / Q000378:metabolism* / Q000503:physiopathology; D010147:Pain Measurement; D017288:Pain Threshold / Q000502:physiology; D010825:Physics; D015221:Potassium Channels / Q000235:genetics / Q000378:metabolism*; D000081033:Potassium Channels, Sodium-Activated; D011984:Sensory Receptor Cells / Q000378:metabolism*
chemical_list: D009419:Nerve Tissue Proteins; D015221:Potassium Channels; D000081033:Potassium Channels, Sodium-Activated; C479624:Slo2 protein, mouse
keywords: Slack channel; analgesia; dorsal root ganglion; neuropathic pain