We know that when we are injured or have an infection, our immune system kicks into gear. This is how our body fights infection and keeps us healthy. Immune cells are also involved in helping us know that there is damage in the tissues by making it hurt. They do this by releasing a bunch of substances (called inflammatory mediators) that trigger receptors on sensory nerves, which cause us to feel pain in the affected area.
So we have always thought that when we have a bacterial infection, we experience pain because the bacteria have caused the immune system to rally and produce substances that activate the nerves. But new research suggests we might need to re-think this.
The very clever Clifford Woolf and his team at the Boston Children’s Hospital and Harvard Medical School have just published a paper in Nature showing that bacteria can directly activate peripheral nociceptors, not via inflammatory mediators or any response involving the immune system, but directly.
They studied this in mice, using the bacterium Staphylococcus aureus, known as golden staph. The results suggest that, at least for this bacterium, it isn’t the host defence system that is responsible for pain, but the bacteria itself.
The team have identified that the golden staph bacteria do this in two ways – secreting one type of substance (called formyl peptides), which triggers mechanical nociceptors, and other type (called alpha haemolysin), which activates thermal nociceptors.
But the next part of the story is even more surprising. They found that when activated by bacteria, the nociceptors suppress rather than trigger immune activity during acute infection. The three neuropeptides that seem to be the culprits of mediating this immune suppression are: calcitonin gene-related peptide (CGRP), galanin and somatostatin.
This is pretty groundbreaking stuff. It means we need to re-think how infection, the immune system and pain all interact. One implication is that if pathogens produce pain, and suppress the immune system in the process, then potentially blocking the nociceptive system could help reduce both pain and infection.
About Julia Hush
Julia is a Senior Lecturer and Department Research Chair at Macquarie University’s new Discipline of Physiotherapy. Her primary research interest is to understand the complex neurobiological mechanisms involved in the development of chronic back pain, and to develop effective mechanism-based treatments for back pain. She is currently on sabbatical at Stanford University in Sean Mackey’s System Neuroscience and Pain Lab (SNAPL).
Chiu IM, Heesters BA, Ghasemlou N, Von Hehn CA, Zhao F, Tran J, Wainger B, Strominger A, Muralidharan S, Horswill AR, Bubeck Wardenburg J, Hwang SW, Carroll MC, & Woolf CJ (2013). Bacteria activate sensory neurons that modulate pain and inflammation. Nature, 501 (7465), 52-7 PMID: 23965627