Bacteria activate sensory neurons that modulate pain and inflammation

Isaac M. Chiu, Balthasar A. Heesters, Nader Ghasemlou, Christian A. Von Hehn, Fan Zhao, Johnathan Tran, Brian Wainger, Amanda Strominger, Sriya Muralidharan, Alexander R. Horswill, Juliane Bubeck Wardenburg, Sun Wook Hwang, Michael C. Carroll, Clifford J. Woolf

Research output: Contribution to journalArticle

263 Citations (Scopus)

Abstract

Nociceptor sensory neurons are specialized to detect potentially damaging stimuli, protecting the organism by initiating the sensation of pain and eliciting defensive behaviours. Bacterial infections produce pain by unknown molecular mechanisms, although they are presumed to be secondary to immune activation. Here we demonstrate that bacteria directly activate nociceptors, and that the immune response mediated through TLR2, MyD88, T cells, B cells, and neutrophils and monocytes is not necessary for Staphylococcus aureus-induced pain in mice. Mechanical and thermal hyperalgesia in mice is correlated with live bacterial load rather than tissue swelling or immune activation. Bacteria induce calcium flux and action potentials in nociceptor neurons, in part via bacterial N-formylated peptides and the pore-forming toxin α-haemolysin, through distinct mechanisms. Specific ablation of Nav1.8-lineage neurons, which include nociceptors, abrogated pain during bacterial infection, but concurrently increased local immune infiltration and lymphadenopathy of the draining lymph node. Thus, bacterial pathogens produce pain by directly activating sensory neurons that modulate inflammation, an unsuspected role for the nervous system in host-pathogen interactions.

Original languageEnglish
Pages (from-to)52-57
Number of pages6
JournalNature
Volume501
Issue number7465
DOIs
Publication statusPublished - 2013 Aug 23

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Sensory Receptor Cells
Nociceptors
Inflammation
Bacteria
Pain
Hyperalgesia
Bacterial Infections
N-Formylmethionine Leucyl-Phenylalanine
Host-Pathogen Interactions
Neurons
Hemolysin Proteins
Bacterial Load
Nervous System
Action Potentials
Staphylococcus aureus
Monocytes
Neutrophils
B-Lymphocytes
Lymph Nodes
Calcium

ASJC Scopus subject areas

  • General

Cite this

Chiu, I. M., Heesters, B. A., Ghasemlou, N., Von Hehn, C. A., Zhao, F., Tran, J., ... Woolf, C. J. (2013). Bacteria activate sensory neurons that modulate pain and inflammation. Nature, 501(7465), 52-57. https://doi.org/10.1038/nature12479

Bacteria activate sensory neurons that modulate pain and inflammation. / Chiu, Isaac M.; Heesters, Balthasar A.; Ghasemlou, Nader; Von Hehn, Christian A.; Zhao, Fan; Tran, Johnathan; Wainger, Brian; Strominger, Amanda; Muralidharan, Sriya; Horswill, Alexander R.; Wardenburg, Juliane Bubeck; Hwang, Sun Wook; Carroll, Michael C.; Woolf, Clifford J.

In: Nature, Vol. 501, No. 7465, 23.08.2013, p. 52-57.

Research output: Contribution to journalArticle

Chiu, IM, Heesters, BA, Ghasemlou, N, Von Hehn, CA, Zhao, F, Tran, J, Wainger, B, Strominger, A, Muralidharan, S, Horswill, AR, Wardenburg, JB, Hwang, SW, Carroll, MC & Woolf, CJ 2013, 'Bacteria activate sensory neurons that modulate pain and inflammation', Nature, vol. 501, no. 7465, pp. 52-57. https://doi.org/10.1038/nature12479
Chiu IM, Heesters BA, Ghasemlou N, Von Hehn CA, Zhao F, Tran J et al. Bacteria activate sensory neurons that modulate pain and inflammation. Nature. 2013 Aug 23;501(7465):52-57. https://doi.org/10.1038/nature12479
Chiu, Isaac M. ; Heesters, Balthasar A. ; Ghasemlou, Nader ; Von Hehn, Christian A. ; Zhao, Fan ; Tran, Johnathan ; Wainger, Brian ; Strominger, Amanda ; Muralidharan, Sriya ; Horswill, Alexander R. ; Wardenburg, Juliane Bubeck ; Hwang, Sun Wook ; Carroll, Michael C. ; Woolf, Clifford J. / Bacteria activate sensory neurons that modulate pain and inflammation. In: Nature. 2013 ; Vol. 501, No. 7465. pp. 52-57.
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