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Can bacteria use pain to tamp down the immune system?

August 22, 2013|By Geoffrey Mohan
  • Methicillin-resistant Staphylococcus aureus (green) forms direct contact with sensory nerve fibers (red).
Methicillin-resistant Staphylococcus aureus (green) forms direct contact… (Balthasar Heesters and…)

Nothing gets our attention like pain.

But pain is more than the body’s miniature cattle prod to get us to heed a wound, rest a swollen ankle, or stop eating chili peppers. Pain may be the language between animals and microbes.

Far from being a product of an inflamed immune system, aggravated nerves far from the spine and brain appear to communicate with invading bacteria and regulate the fight against them, according to a study published online Wednesday in the journal Nature. And at least one tenacious bacterium shows the ability to manipulate a pain signal to put the brakes on a mammal's molecular defenses, the study suggests.

The report, which examined Methicillin-resistant Staphylococcus aureus bacteria in mice, adds to a growing body of evidence linking such microbial elements as human gut bacteria with mood and brain development. Recent research has shown that DNA from microbes can be transferred to animals. And a University of Maryland study published in June showed DNA from microbes could transfer into some human somatic cells - though previous claims of widespread lateral gene transfer between microbes and the human genome have been refuted.

At the least, the study suggests the lines of communication from microbe to nerve to brain are direct, open and dynamic.

“The most provocative part of the story is not that chemicals made by bacteria cause pain, because lots of chemicals can cause pain,” said immunologist and neurosurgeon Kevin Tracey, president of the Feinstein Institute for Medical Research in Manhasset, N.Y., who was not involved in the study. “What is provocative, and a very elegant discovery, is that the bacteria are sensed by the nervous system. The nervous system knows the bacteria are there. And this launches the taut line of signals that control the development of immunity.”

The researchers, led by Boston Children’s Hospital and Harvard University, began by injecting staph bacteria into a mouse paw to examine the relationship between inflammation and pain.

“A lot of people had assumed that it’s indirect, that immune cells are activated, and they release factors that act on the neurons to cause them to act more sensitively,” said Boston Children's Hospital immunologist Isaac M. Chiu, lead author of the paper. “But instead what we found was that there are molecules made by the bacteria themselves during the infection that are acting on the nerve fibers and causing them to fire off signals of pain.”

Long before the brain signals what to do about the intruder, then, outlying nerves are communicating with bacteria – a sixth mode of sensation, Tracey calls it.

One message from S. aureus, detected by the research team, was to tamp down the mouse's inflammatory assault. Molecules produced by S. aureus activated nerves that produced a compound that put on immunological brakes that are designed to prevent destruction of native tissue or beneficial intruders – such as the millions of bacteria that live peaceably in the human body. Such a brake, common even in simple animals, likely is an evolutionary gift that prevents runaway inflammation, the core of such diseases as rheumatoid arthritis, Tracey said.

There are many caveats offered by the study authors, paramount among them that they examined mice and a single bacterium strain. Staph is known to have many other biochemical tricks to survive, among them rapid evolution to resist multiple antibiotics. And the team did not examine the full spread and pathology of the infection, Chiu noted.

Still, the work so far hints at new treatment pathways for infection-related pain. The team likewise will explore whether the nerve activity that appears to mediate inflammation can be manipulated over the long time period typical of a chronic disease.

“So there’s a lot of interesting questions that come out of this,” Chiu said.

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