Deletion of interleukin-6 signal transducer gp130 in small sensory neurons attenuates mechanonociception and down-regulates TRPA1 expression

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dc.contributor.authorMalsch, P.
dc.contributor.authorAndratsch, M.
dc.contributor.authorVogl, C.
dc.contributor.authorLink, A.S.
dc.contributor.authorAlzheimer, C.
dc.contributor.authorBrierley, S.M.
dc.contributor.authorHughes, P.A.
dc.contributor.authorKress, M.
dc.date.issued2014
dc.description.abstractGlycoprotein 130 (gp130) is the signal transducing receptor subunit for cytokines of the interleukin-6 (IL-6) family, and it is expressed in a multitude of cell types of the immune and nervous system. IL-6-like cytokines are not only key regulators of innate immunity and inflammation but are also essential factors for the differentiation and development of the somatosensory system. Mice with a null mutation of gp130 in primary nociceptive afferents (SNS-gp130(-/-)) are largely protected from hypersensitivity to mechanical stimuli in mouse models of pathological pain. Therefore, we set out to investigate how neuronal gp130 regulates mechanonociception. SNS-gp130(-/-) mice revealed reduced mechanosensitivity to high mechanical forces in the von Frey assay in vivo, and this was associated with a reduced sensitivity of nociceptive primary afferents in vitro. Together with these findings, transient receptor potential ankyrin 1 (TRPA1) mRNA expression was significantly reduced in DRG from SNS-gp130(-/-) mice. This was also reflected by a reduced number of neurons responding with calcium transients to TRPA1 agonists in primary DRG cultures. Downregulation of Trpa1 expression was predominantly discovered in nonpeptidergic neurons, with the deficit becoming evident during stages of early postnatal development. Regulation of Trpa1 mRNA expression levels downstream of gp130 involved the classical Janus kinase family-signal transducer and activator of transcription pathway. Our results closely link proinflammatory cytokines to the expression of TRPA1, both of which have been shown to contribute to hypersensitive pain states. We suggest that gp130 has an essential role in mechanonociception and in the regulation of TRPA1 expression.
dc.description.statementofresponsibilityPhilipp Malsch, Manfred Andratsch, Christian Vogl, Andrea S. Link, Christian Alzheimer, Stuart M. Brierley, Patrick A. Hughes, and Michaela Kress
dc.identifier.citationJournal of Neuroscience, 2014; 34(30):9845-9856
dc.identifier.doi10.1523/JNEUROSCI.5161-13.2014
dc.identifier.issn0270-6474
dc.identifier.issn1529-2401
dc.identifier.orcidBrierley, S.M. [0000-0002-2527-2905]
dc.identifier.orcidHughes, P.A. [0000-0001-7324-3626]
dc.identifier.urihttp://hdl.handle.net/2440/86433
dc.language.isoen
dc.publisherSociety for Neuroscience
dc.rights© 2014 the authors. Authors grant JNeurosci a license to publish their work and copyright remains with the author. Material published from 2010 to 2014 is licensed under a Creative Commons Attribution-Noncommercial-Share Alike 3.0 Unported License (CC-BY-NC-SA).
dc.source.urihttps://doi.org/10.1523/jneurosci.5161-13.2014
dc.subjectcytokine; Il-6 signal transducer; JAK/STAT signaling; mechanonociceptor; mechanotransduction; pain
dc.titleDeletion of interleukin-6 signal transducer gp130 in small sensory neurons attenuates mechanonociception and down-regulates TRPA1 expression
dc.typeJournal article
pubs.publication-statusPublished

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