Bacteria activate sensory neurons that modulate pain and inflammation

摘要

细菌感染(如由葡萄球菌造成的感染)产生的疼 痛对于免疫反应和炎症来说被认为是继发性 的。现在，Clifford Woolf及同事报告了在细菌 感染过程中的一个以前没有被意识到的疼痛诱 导机制：伤害感受器在病原体介导下的直接激 发。他们发现，小鼠由金黄葡萄球菌感染产生rn的疼痛是独立于大多数已知的免疫中介物的： 该细菌产生两类分子-甲酰化的肽和成孔毒 素，它们通过直接激发伤害感受器神经元诱导 疼痛，后者则又调控炎症。%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 a-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.