The pain of invasive skin infections, such as those caused by methicillin-resistant Staphylococcus aureus, appears to be induced by the invading bacteria themselves, and not by the body’s immune response, report HMS scientists at Boston Children’s Hospital. What’s more, their research demonstrates that once the pain neurons “sense” the bacteria, they suppress the immune system, potentially helping the bacteria become more virulent.
The study, which used a mouse model, could change the way doctors think about a variety of invasive painful infections, such as meningitis, necrotizing fasciitis, urinary tract infections, dental caries, and intestinal infections. The research was published in the September 5 issue of Nature.
“If we could block pain in infected tissues and also block what pain neurons do to the immune system, it could help us treat bacterial infections better,” says Isaac Chiu, the study’s first author and a neuroimmunologist in the laboratory of Clifford Woolf, an HMS professor of neurology at Boston Children’s F.M. Kirby Neurobiology Program.
The research was spurred when the scientists observed the interaction of cultured sensory neurons and immune cells during an infection. “Surprisingly, the neurons responded immediately to the bacteria,” says Chiu. That observation led the researchers to move to a live model of skin infection, the first, they think, ever used to study pain.
In the study, Chiu and colleagues examined pain, tissue swelling, immune cell numbers, and the number of live bacteria in mice with staphylococcal skin infections. They found that pain levels tracked closely with the number of live bacteria and peaked well before tissue swelling did, indicating that the bacteria, not a local inflammatory response, were the cause of the pain. The team also documented communication between bacteria, pain neurons, and cells from the immune system.
The research showed that S. aureus secretes two kinds of compounds that communicate with sensory neurons and help induce pain. These N-formyl peptides, which can be detected by receptors on pain neurons, and pore-forming toxins, which are secreted by virulent bacteria, dock on the sensory nerve terminals and create pores that let ions enter the nerve cells, triggering them to fire off pain messages.
The finding that pain neurons, once activated by bacteria, suppress the immune system was equally unexpected. Why would activated pain neurons try to weaken the immune response to infection? Chiu speculates that the neurons are functioning to protect tissues from further damage caused by an inflammatory immune response—a protective mechanism that bacteria might be exploiting to their advantage.