title: Oncostatin M induces heat hypersensitivity by gp130-dependent sensitization of TRPV1 in sensory neurons.
abstract: Oncostatin M (OSM) is a member of the interleukin-6 cytokine family and regulates eg. gene activation, cell survival, proliferation and differentiation. OSM binds to a receptor complex consisting of the ubiquitously expressed signal transducer gp130 and the ligand binding OSM receptor subunit, which is expressed on a specific subset of primary afferent neurons. In the present study, the effect of OSM on heat nociception was investigated in nociceptor-specific gp130 knock-out (SNS-gp130-/-) and gp130 floxed (gp130fl/fl) mice.Subcutaneous injection of pathophysiologically relevant concentrations of OSM into the hind-paw of C57BL6J wild type mice significantly reduced paw withdrawal latencies to heat stimulation. In contrast to gp130fl/fl mice, OSM did not induce heat hypersensitivity in vivo in SNS-gp130-/- mice. OSM applied at the receptive fields of sensory neurons in in vitro skin-nerve preparations showed that OSM significantly increased the discharge rate during a standard ramp-shaped heat stimulus. The capsaicin- and heat-sensitive ion channel TRPV1, expressed on a subpopulation of nociceptive neurons, has been shown to play an important role in inflammation-induced heat hypersensitivity. Stimulation of cultured dorsal root ganglion neurons with OSM resulted in potentiation of capsaicin induced ionic currents. In line with these recordings, mice with a null mutation of the TRPV1 gene did not show any signs of OSM-induced heat hypersensitivity in vivo.The present data suggest that OSM induces thermal hypersensitivity by directly sensitizing nociceptors via OSMR-gp130 receptor mediated potentiation of TRPV1.
authors.affiliation: Division of Physiology, Department of Physiology and Medical Physics, Medical University Innsbruck, Innsbruck, Austria. michiel.langeslag@i-med.ac.at
authors.forename: Michiel
authors.initials: M
authors.lastname: Langeslag
authors.forename: Cristina E
authors.initials: CE
authors.lastname: Constantin
authors.forename: Manfred
authors.initials: M
authors.lastname: Andratsch
authors.forename: Serena
authors.initials: S
authors.lastname: Quarta
authors.forename: Norbert
authors.initials: N
authors.lastname: Mair
authors.forename: Michaela
authors.initials: M
authors.lastname: Kress
mesh_terms: D000818:Animals; D050822:Cytokine Receptor gp130 / Q000235:genetics* / Q000378:metabolism; D006358:Hot Temperature; D006930:Hyperalgesia / Q000378:metabolism* / Q000503:physiopathology; D051379:Mice; D018345:Mice, Knockout; D059225:Nociception / Q000502:physiology; D053683:Oncostatin M / Q000378:metabolism* / Q000494:pharmacology; D011984:Sensory Receptor Cells / Q000187:drug effects / Q000378:metabolism*; D015398:Signal Transduction; D050916:TRPV Cation Channels / Q000235:genetics / Q000378:metabolism*
chemical_list: D050916:TRPV Cation Channels; C493921:TRPV1 protein, mouse; D053683:Oncostatin M; D050822:Cytokine Receptor gp130