“My feet hurt a lot in the morning, and my teeth hurt a lot at night”… Why?

The body's internal clock, the "biological clock," influences inflammation in the immune system. Patients with plantar fasciitis experience more discomfort in the morning, while those with toothache or gout experience more discomfort at night. While this varies from person to person, some inflammatory conditions have specific times when pain is particularly severe.

A new study suggests that macrophages, immune cells, interact with the body at different times throughout the day, potentially leading to significantly different times of day when patients with inflammatory conditions experience more intense pain. A research team from the Royal College of Surgeons of Ireland (RCSI) announced this finding after exploring the link between the immune system and circadian rhythms.

 

Patients with ankylosing spondylitis, which causes back pain, and plantar fasciitis, which causes pain due to inflammation of the plantar fascia, tend to feel pain more severe in the morning. Also, patients with gout and frozen shoulder (adhesive capsulitis), which cause severe pain in the big toe and other joints, experience more severe pain at night, which leads to insomnia that interferes with a good night's sleep.

Professor Annie Curtis (Department of Pharmacy and Biomolecular Sciences), the study's lead author, said, "We anticipate that these findings will pave the way for 'temporally targeted treatments' for inflammatory diseases, where the timing of pain varies depending on the activity of macrophages." According to the research team, macrophages, immune cells that detect and respond to harmful substances in the body, can induce inflammation as a defense mechanism by assembling large complexes known as inflammatory substances. Inflammatory substances are similar to alarms (smoke detectors) that alert the immune system to danger.

 

Research has shown that activation of a specific inflammasome (NLRP3) is not constant throughout the day, but rather is regulated by a 24-hour biological clock. This daily rhythm determines when macrophages are most effective at detecting threats and when their energy levels are at their peak to initiate a response. Furthermore, mitochondria, the cellular energy producers, appear to play a crucial role in driving daily fluctuations in immune activity.

 

Professor Curtis “When macrophages ‘think’ it’s morning, their inflammasome activation becomes faster and more powerful,” he explained. “This means that the immune response is enhanced in the early morning hours when we’re awake.” This is the time when we are awake and more likely to face environmental challenges such as injury or infection,” he said. The findings could help better understand and treat inflammatory diseases such as arthritis, where “overactive” inflammatory proteins play a key role, the researchers said.

Immune response is strengthened during waking hours

My body seems to be going into protection mode on its own.