Oncostatin M induces heat hypersensitivity by gp130-dependent sensitization of TRPV1 in sensory neuronsReportar como inadecuado




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Molecular Pain

, 7:102

First Online: 23 December 2011Received: 29 June 2011Accepted: 23 December 2011

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 gp130 mice.

Subcutaneous injection of pathophysiologically relevant concentrations of OSM into the hind-paw of C57BL6Jwild type mice significantly reduced paw withdrawal latencies to heat stimulation. In contrast to gp130 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.

Keywordsinflammation inflammatory pain proinflammatory cytokines heat hypersensitivity transsignaling List of abbreviationsOSMOncostatin M

OSMROncostatin M receptor

LIFleukemia inhibitory factor

IL-6Interleukin-6

gp130glycoprotein 130

TRPV1transient receptor potential vanilloid 1

SNSsensory neuron specific

DRGdorsal root ganglia

Icapscapsaicin-activated inward current

PWLpaw withdrawal latency

RTroom temperature

PBSphosphate buffered saline

DMEMDulbecco-s modified Eagle medium

BSAbovine serum albumin

PFAparaformaldehyde

Electronic supplementary materialThe online version of this article doi:10.1186-1744-8069-7-102 contains supplementary material, which is available to authorized users.

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Autor: Michiel Langeslag - Cristina E Constantin - Manfred Andratsch - Serena Quarta - Norbert Mair - Michaela Kress

Fuente: https://link.springer.com/



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