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 flox/flox (gp130^fl/fl) mice. Subcutaneous injection of OSM (10ng/10ml) into the hind-paw of gp130^fl/fl mice significantly reduced paw withdrawal latencies to heat stimulation from 9.82 ± 0.88s to 5.13 ± 1.54s within 30 min. Moreover, in SNS-gp130^-/- mice OSM did not change heat sensitivity in vivo. In vitro skin-nerve preparation showed that OSM (5ng/ml) at the receptive fields of sensory neurons significantly increased the discharge rate during a standard ramp-shaped heat stimulus from 2.10 ± 0.44 imp/s to 3.69 ± 0.76 imp/s within 5 min.

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 hyperalgesia. A preconditioning stimulation of cultured dorsal root ganglion neurons with OSM (5ng/ml) potentiated capsaicin induced ionic currents from 0.92 ± 0.19 nA to 1.80 ± 0.37 nA within 1 min. Deletion of the TRPV1 gene abolished OSM-induced heat hypersensitivity in vivo. The present data suggest that OSM induces thermal hypersensitivity by directly sensitising nociceptors via receptor mediated potentiation of TRPV1.