期刊
MOLECULAR PAIN
卷 7, 期 -, 页码 -出版社
BIOMED CENTRAL LTD
DOI: 10.1186/1744-8069-7-102
关键词
inflammation; inflammatory pain; proinflammatory cytokines; heat hypersensitivity; transsignaling
资金
- Fonds zur Forderung der wissenschaftlichen Forschung, Austria (FWF) [P18444]
- Austrian Science Fund (FWF) [W1206, P18444] Funding Source: Austrian Science Fund (FWF)
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(fl/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 gp130(fl/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.
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