title: Bacteria activate sensory neurons that modulate pain and inflammation.
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.
authors: Kirby Neurobiology Center, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA.
authors: Isaac M
authors: IM
authors: Chiu
authors: Balthasar A
authors: BA
authors: Heesters
authors: Nader
authors: N
authors: Ghasemlou
authors: Christian A
authors: CA
authors: Von Hehn
authors: Fan
authors: F
authors: Zhao
authors: Johnathan
authors: J
authors: Tran
authors: Brian
authors: B
authors: Wainger
authors: Amanda
authors: A
authors: Strominger
authors: Sriya
authors: S
authors: Muralidharan
authors: Alexander R
authors: AR
authors: Horswill
authors: Juliane
authors: J
authors: Bubeck Wardenburg
authors: Sun Wook
authors: SW
authors: Hwang
authors: Michael C
authors: MC
authors: Carroll
authors: Clifford J
authors: CJ
authors: Woolf
mesh_terms: D000200:Action Potentials; D000818:Animals; D058491:Bacterial Load; D020013:Calcium Signaling; D005260:Female; D006460:Hemolysin Proteins / Q000378:metabolism; D054884:Host-Pathogen Interactions; D006358:Hot Temperature; D006930:Hyperalgesia / Q000382:microbiology; D007113:Immunity, Innate; D007249:Inflammation / Q000276:immunology / Q000378:metabolism / Q000382:microbiology* / Q000473:pathology; D008206:Lymphatic Diseases / Q000276:immunology / Q000382:microbiology / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009000:Monocytes; D053594:Myeloid Differentiation Factor 88 / Q000276:immunology; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000378:metabolism; D062559:NAV1.8 Voltage-Gated Sodium Channel / Q000172:deficiency / Q000276:immunology / Q000378:metabolism; D009504:Neutrophils; D009619:Nociceptors / Q000378:metabolism*; D010146:Pain / Q000276:immunology / Q000378:metabolism / Q000382:microbiology* / Q000503:physiopathology*; D055550:Protein Stability; D013203:Staphylococcal Infections / Q000276:immunology / Q000378:metabolism / Q000382:microbiology; D013211:Staphylococcus aureus / Q000276:immunology / Q000378:metabolism / Q000472:pathogenicity*; D051195:Toll-Like Receptor 2 / Q000276:immunology
chemical_list: D006460:Hemolysin Proteins; C507780:Myd88 protein, mouse; D053594:Myeloid Differentiation Factor 88; D062559:NAV1.8 Voltage-Gated Sodium Channel; C568318:Scn10a protein, mouse; C493486:Tlr2 protein, mouse; D051195:Toll-Like Receptor 2; D009240:N-Formylmethionine Leucyl-Phenylalanine
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