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Semaphorin 4C Plexin-B2 signaling in peripheral sensory neurons is pronociceptive in a model of inflammatory pain

Author

Listed:
  • Eszter Paldy

    (Heidelberg University)

  • Manuela Simonetti

    (Heidelberg University)

  • Thomas Worzfeld

    (Marburg University
    Max-Planck-Institute for Heart and Lung Research)

  • Kiran Kumar Bali

    (Heidelberg University)

  • Lucas Vicuña

    (Heidelberg University)

  • Stefan Offermanns

    (Max-Planck-Institute for Heart and Lung Research)

  • Rohini Kuner

    (Heidelberg University)

Abstract

Semaphorins and their transmembrane receptors, Plexins, are key regulators of axon guidance and development of neuronal connectivity. B-type Plexins respond to Class IV semaphorins and mediate a variety of developmental functions. Here we report that the expression of Plexin-B2 and its high-affinity ligand, Sema4C, persists in peripheral sensory neurons in adult life and is markedly increased in states of persistent pain in mice. Genetic deletion of Sema4C as well as adult-onset loss of Plexin-B2 leads to impairment of the development and duration of inflammatory hypersensitivity. Remarkably, unlike the neurodevelopmental functions of Plexin-B2 that solely rely on Ras signaling, we obtained genetic and pharmacological evidence for a requirement of RhoA-ROCK-dependent mechanisms as well as TRPA1 sensitization in pronociceptive functions of Sema4C-Plexin-B2 signaling in adult life. These results suggest important roles for Plexin-B2 signaling in sensory function that may be of therapeutic relevance in pathological pain.

Suggested Citation

  • Eszter Paldy & Manuela Simonetti & Thomas Worzfeld & Kiran Kumar Bali & Lucas Vicuña & Stefan Offermanns & Rohini Kuner, 2017. "Semaphorin 4C Plexin-B2 signaling in peripheral sensory neurons is pronociceptive in a model of inflammatory pain," Nature Communications, Nature, vol. 8(1), pages 1-15, December.
    • Handle: RePEc:nat:natcom:v:8:y:2017:i:1:d:10.1038_s41467-017-00341-w
    DOI: 10.1038/s41467-017-00341-w
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