Hey, bacteria, stop getting on my nerves!
During my graduate course on Inflammation, the first concept we learned was on the five cardinal signs of inflammation: rubor (redness), calor (heat), tumor (swelling), dolor (pain), and function laesa (loss of function). The first four cardinal signs were described in the first century AD by Aulus Cornelius Celsus, a Roman encyclopedist. The fifth cardinal sign, loss of function, was introduced by Rudolf Virchow in the nineteenth century.
*Just as an aside, I recently spent two weeks in Berlin at Humbolt University, the Max Planck Institute for Infection and Immunity, and the Charité as part of a graduate trainee summer program. Virchow, the ‘father of modern pathology’, studied and practiced medicine at Humbolt University and the Charité during his career in the mid-1800s. This was an amazing experience for me, being at the very same institutes where several significant medicinal discoveries were made.
Ok, so how do you know you have an infection? You’ll notice the infected area on your body getting red, hot, swollen… sometimes you won’t be able to use your arm or leg properly (ie. loss of function). Most of the time, you will feel pain, because infections can hurt!
Today, I’m writing this blog post on how the immune response and the pain response are linked during an infection.
What is pain? In simple terms, pain is a distressing feeling caused by some kind of tissue damage or insult. Pain can be classified as either acute or chronic. Chronic pain is seen in many diseases such as cancer and autoimmune disease such as rheumatoid arthritis or multiple sclerosis. For most infections, you will experience acute pain, which often resolves when the pathogen is removed from the body.
You feel pain when sensory neurons (called nociceptors) become activated when they are exposed to something dangerous. This is a good thing because it alerts your immune system to protect your body from infection.
It turns out that during some skin infections, such as Staphylococcus aureus (S. aureus), bacteria are able to directly activate nociceptors, creating additional pain. This study was published by Isaac Chiu in Nature in 2013 if you are interested in reading more, because I'll be writing about a more recent paper published just a couple months ago.
Dr. Chiu now has his own lab at Harvard University, and his group published a paper in Nature Medicine describing a role for nociceptors in the lung during S. aureus pneumonia. But for this type of infection, lung-innervating nociceptors (meaning pain receptors that are found within the lung) actually suppressed the immune response by having less neutrophil recruitment to the lung and an altered T cell population (γδ T cells, in particular).
The authors found that by blocking specific neurons found in the lung (TRPV1+ neurons) with a drug, Resinieratoxin (RTX), mice were protected from S. aureus pneumonia. RTX treatment restored neutrophil recruitment to the lung and improved γδ T cell function, both of which were essential for controlling S. aureus pneumonia. This study is promising for the treatment of pneumonia.
Dr. Chiu's work bridging immunology and pain is essential to discover novel treatments to infection that target the nervous system. But before we prescribe the right drug, we need to figure out exactly how our immune system responds to pain, how bacteria can manipulate pain, and also what other side effects may occur with these treatments.
Coming up next on the blog will be all about why you should be eating extra fibre during flu season. Stay tuned!