Oncostatin M induces heat hypersensitivity by gp130-dependent sensitization of TRPV1 in sensory neurons
<p>Abstract</p> <p>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 ligan...
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| Main Authors: | , , , , , |
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| Format: | Book |
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SAGE Publishing,
2011-12-01T00:00:00Z.
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| Summary: | <p>Abstract</p> <p>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 (<it>SNS-gp130<sup>-/-</sup></it>) and gp130 floxed (<it>gp130<sup>fl/fl</sup></it>) mice.</p> <p>Subcutaneous injection of pathophysiologically relevant concentrations of OSM into the hind-paw of <it>C57BL6J </it><it>wild type </it>mice significantly reduced paw withdrawal latencies to heat stimulation. In contrast to <it>gp130<sup>fl/fl </sup></it>mice, OSM did not induce heat hypersensitivity <it>in vivo </it>in <it>SNS-gp130<sup>-/- </sup></it>mice. OSM applied at the receptive fields of sensory neurons in <it>in vitro </it>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 <it>in vivo</it>.</p> <p>The present data suggest that OSM induces thermal hypersensitivity by directly sensitizing nociceptors via OSMR-gp130 receptor mediated potentiation of TRPV1.</p> |
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| Item Description: | 10.1186/1744-8069-7-102 1744-8069 |