IL-6 like cytokines and chronic pain

With progression of many diseases the accompanying pain gets increasingly difficult to treat and novel analgesic principles for an improved therapy are urgently needed. The project aims at identifying the role of the proinflammatory cytokine interleukin IL-6 and its receptors in chronic pain states. For this purpose we will focus on the analysis of IL-6 effects on the function and survival of nociceptive neurons. We will elucidate the role of membrane bound and soluble IL-6 receptors, the signalling receptor ß-subunit glycoprotein gp130 and down- stream signalling pathways. In addition, we will analyse other gp130 utilising members of the IL-6 like cytokine family (leukaemia inhibitory factor LIF, Interleukin IL-11, Oncostatin M (OSM), ciliary neurotrophic factor CNTF, cardiotrophin-1 (CT-1) and cardiotrophin-like cytokine CLC) as well as their ligand binding receptor subunits and downstream signalling in terms of neuron function, survival and/or regeneration. Overall the suggested project aims at identifying the role of IL-6 like cytokines, their receptors and cellular signalling in pain chronicity.

With progression of many diseases the accompanying pain gets increasingly difficult to treat and novel analgesic principles for an improved therapy are urgently needed. The project aimed at identifying the role of the proinflammatory cytokine interleukin IL-6 and its receptors in chronic pain states. For this purpose we focused on the analysis of IL-6 effects on the function of pain-sensing nociceptive neurons. We investigated the role of membrane bound and soluble IL-6 receptors, the signalling receptor ß-subunit glycoprotein gp130 and down- stream signalling pathways. In addition, we analysed other gp130 utilising members of the IL-6 like cytokine family (leukaemia inhibitory factor - LIF, Oncostatin M - OSM). Since global null mutants for the receptor protein gp130 are not viable, mice lacking gp130 in the cell membrane of nociceptive neurons were generated which presented with reduced pain sensitivity in inflammatory or tumour pain models. Neuropathic pain was not affected by the conditional deletion of gp130 in sensory neurons. It is expected that the global neutralisation of gp130 in addition to antiinflammtory effects will attenuate pathological pain states associated with chronic inflammatory diseases. Our results strongly support the development of gp130 neutralising drugs for the treatment of pathological inflammatory or tumour associated pain states.