Interleukin-27 controls basal pain threshold in physiological and pathological conditions

Tomoko Sasaguri, Toru Taguchi, Yuzo Murata, Kimiko Kobayashi, Sayaka Iizasa, Ei’ichi Iizasa, Makoto Tsuda, Naomi Hirakawa, Hiromitsu Hara, Hiroki Yoshida, Toshiharu Yasaka

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Abstract

Numerous studies have shown that pain sensation is affected by various immune molecules, such as cytokines, in tissues comprising the sensory pathway. Specifically, it has been shown that interleukin (IL)-17 promotes pain behaviour, but IL-10 suppresses it. IL-27 has been reported to have an anti-inflammatory effect through regulation of T cell differentiation, resulting in reduced IL-17 and induction of IL-10. Thus, we hypothesised that IL-27 would have some regulatory role in pain sensation. Here, we provide evidence that endogenous IL-27 constitutively controls thresholds for thermal and mechanical sensation in physiological and pathological conditions. Mice lacking IL-27 or its receptor WSX-1 spontaneously showed chronic pain-like hypersensitivity. Reconstitution of IL-27 in IL-27-deficient mice reversed thermal and mechanical hypersensitive behaviours. Thus, unlike many other cytokines induced by inflammatory events, IL-27 appears to be constitutively produced and to control pain sensation. Furthermore, mice lacking IL-27/WSX-1 signalling showed additional hypersensitivity when subjected to inflammatory or neuropathic pain models. Our results suggest that the mechanisms underlying hypersensitive behaviours caused by the ablation of IL-27/WSX-1 signalling are different from those underlying established chronic pain models. This novel pain control mechanism mediated by IL-27 might indicate a new mechanism for the chronic pain hypersensitivity.

Original languageEnglish
Article number11022
JournalScientific reports
Volume8
Issue number1
DOIs
Publication statusPublished - Dec 1 2018

All Science Journal Classification (ASJC) codes

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    Sasaguri, T., Taguchi, T., Murata, Y., Kobayashi, K., Iizasa, S., Iizasa, E., Tsuda, M., Hirakawa, N., Hara, H., Yoshida, H., & Yasaka, T. (2018). Interleukin-27 controls basal pain threshold in physiological and pathological conditions. Scientific reports, 8(1), [11022]. https://doi.org/10.1038/s41598-018-29398-3