Bacteria activate sensory neurons that modulate pain and inflammation

By I. Chiu, B. Heesters, N. Ghasemlou, Christian A. von Hehn, Fan Zhao, Johnathan Tran, Brian J. Wainger, A. Strominger, Sriya Muralidharan, A. Horswill and 4 more. Nature, 2013

831 citations recorded by the source corpus.

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.

Subfields: Molecular Biology, Neurology, Physiology

View Paper: https://www.semanticscholar.org/paper/3479674b4887712522807f96e163e53b547c0b1c

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Molecular Biology

1. J. Cryan
2. Ted G. Dinan
3. R. Stilling
4. Yan Wang
5. L. Kasper
6. C. Deutschman
7. Victor J. Torres
8. Francis Alonzo

In Neurology

1. C. Deutschman
2. Kevin J. Tracey
3. Bruce S. McEwen
4. Peter J. Gianaros

In Physiology

1. Ted G. Dinan
2. J. Cryan
3. Yan Wang
4. L. Kasper
5. Kevin J. Tracey

Citations in the corpus

• The Bicomponent Pore-Forming Leucocidins of Staphylococcus aureus (2014, background): “aureus is indeed able to directly induce sensations of pain through the action of a pore-forming toxin (in this case, alpha-hemolysin) on nociceptive neurons; however, the bicomponent leucocidins were not implicated (286).”
• The role of microbiome in central nervous system disorders (2013, positive): “Chiu et al. (2013) indicated that Staphylococcus aureus activation of sensory neurons could transduce nociception.”
• Sepsis: current dogma and new perspectives. (2014, background): “LPS, IL-1b, and other PAMPs and alarmins can directly activate capsacin-sensitive vagus nerve sensory fibers, dorsal root ganglion neurons, and neurons residing in the nodose ganglion (Chiu et al., 2013).”
• Nociceptor Sensory Neuron-Immune Interactions in Pain and Inflammation (2016, positive): “aureus, and CGRP administration restored lymph node hypertrophy, including the recruitment of T cells and B cells during infection, although the effects on subsequent adaptive immunity have not yet been determined [75].”
• Microbial genes, brain & behaviour – epigenetic regulation of the gut–brain axis (2014, background): “Just recently a well known bacterium (Staphylococcus aureus) was shown to stimulate nociceptive neurons directly (Chiu et al. 2013), which encourages us to rethink what we know about gut bacteria and whether they may stimulate neurons of the autonomous nervous system by similar mechanisms, which cou”