title: BKCa channels expressed in sensory neurons modulate inflammatory pain in mice.
abstract: Large conductance calcium-activated potassium (BKCa) channels are important regulators of neuronal excitability. Although there is electrophysiological evidence for BKCa channel expression in sensory neurons, their in vivo functions in pain processing have not been fully defined. Using a specific antibody, we demonstrate here that BKCa channels are expressed in subpopulations of peptidergic and nonpeptidergic nociceptors. To test a functional association of BKCa channel activity in sensory neurons with particular pain modalities, we generated mice in which BKCa channels are ablated specifically from sensory neurons and analyzed their behavior in various models of pain. Mutant mice showed increased nociceptive behavior in models of persistent inflammatory pain. However, their behavior in models of neuropathic or acute nociceptive pain was normal. Moreover, systemic administration of the BKCa channel opener, NS1619, inhibited persistent inflammatory pain. Our investigations provide in vivo evidence that BKCa channels expressed in sensory neurons exert inhibitory control on sensory input in inflammatory pain states.
authors: Pharmazentrum Frankfurt/ZAFES, Institut für Klinische Pharmakologie, Klinikum der Johann Wolfgang Goethe-Universität, Frankfurt am Main, Germany Pharmakologie, Toxikologie und Klinische Pharmazie, Institut für Pharmazie, Tübingen, Germany Pharmakologisches Institut, Universität Heidelberg, Heidelberg, Germany.
authors: Ruirui
authors: R
authors: Lu
authors: Robert
authors: R
authors: Lukowski
authors: Matthias
authors: M
authors: Sausbier
authors: Dong Dong
authors: DD
authors: Zhang
authors: Marco
authors: M
authors: Sisignano
authors: Claus-Dieter
authors: CD
authors: Schuh
authors: Rohini
authors: R
authors: Kuner
authors: Peter
authors: P
authors: Ruth
authors: Gerd
authors: G
authors: Geisslinger
authors: Achim
authors: A
authors: Schmidtko
mesh_terms: D000818:Animals; D005260:Female; D005786:Gene Expression Regulation; D007249:Inflammation / Q000378:metabolism / Q000473:pathology; D051037:Large-Conductance Calcium-Activated Potassium Channel alpha Subunits / Q000096:biosynthesis*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010146:Pain / Q000378:metabolism* / Q000473:pathology; D010147:Pain Measurement / Q000379:methods*; D011984:Sensory Receptor Cells / Q000378:metabolism* / Q000473:pathology
chemical_list: C530995:BKCa protein, mouse; D051037:Large-Conductance Calcium-Activated Potassium Channel alpha Subunits
keywords: Conditional knockout mice; Dorsal root ganglion; Inflammatory pain; Large conductance Ca(2+)-activated K(+) channels