In this, the first in a series of guest blog posts from members of ME Research UK’s Researcher Circle, PhD student Yanthe Buntinx writes about chronic pain in ME/CFS, discussing links with the immune system and lifestyle factors.
Under the supervision of Prof. Jo Nijs and Associate Prof. Andrea Polli, and alongside colleagues Jente Van Campenhout, Jolien Hendrix, all of whom have received funding from ME Research UK, Yanthe Buntinx is a PhD candidate in the Pain in Motion Research Group at Vrije Universiteit Brussel Brussels, Belgium. Excitingly, Yanthe’s project which explores the role of T cell dysfunction and its underlying epigenetic mechanisms in ME/CFS recently became a joint PhD collaboration, with Prof. Lode Godderis at KU Leuven joining the supervision team.
In her article, Yanthe explores how the findings identified in her recently published review paper, entitled “Exploring Chronic Pain, Immune Dysfunction and Lifestyle: A Focus on T Cell Exhaustion and Senescence“, may also apply to ME/CFS.
Background
Our immune system protects us from injury and infections such as those caused by bacteria and viruses. In people with ME/CFS, growing evidence shows that the immune system does not work as it should. This is important because the immune system also plays a role in how pain develops and persists, which may help explain why many individuals with ME/CFS experience ongoing pain.
T cells and chronic pain
Pain is controlled by constant communication between cells of the immune system and specialized nerve endings – nociceptors – that warn our bodies of harmful signals in the environment. Among the many types of immune cells, T cells play a particularly important role in pain: they can both increase pain and help protect against it.
Normally, T cells are carefully regulated, but when this regulation goes wrong, they can become less active. There are two important processes where T cells become less active:
- Exhaustion: where T cells become ‘tired’ and no longer respond properly.
- Senescence: where T cells act like ‘aged’ cells, similar to what happens naturally as we grow older.
Both T cell exhaustion and T cell senescence have been widely studied in other illnesses, such as cancer, where understanding and regulating these processes has led to new, groundbreaking treatments. Therefore, looking closely at how T cells behave in ME/CFS could reveal important insights into the disease. Some small exploratory studies have already done this; but a large, detailed study is still missing, so no clear conclusion can be drawn yet.
In a recent article by myself and other members of the Pain in Motion research group at the Vrije Universiteit Brussel, we looked at existing information on chronic pain disorders (such as ME/CFS, fibromyalgia, rheumatoid arthritis, etc.) and immune function through a new lens: we focused specifically on T cell exhaustion, T cell senescence, and everyday lifestyle factors.
Lifestyle factors and chronic pain
Chronic pain is shaped by many aspects of daily life, including sleep, stress, physical activity and diet. Each of these factors not only affects pain but also influences how well our immune system works. This suggests a strong connection between a balanced lifestyle, the immune system and chronic pain in ME/CFS.
Understanding this link could help researchers uncover the biological processes that drive chronic pain, especially those related to the immune system. We found that some features of T cell exhaustion and T cell senescence may be linked to lifestyle factors, but current studies often show unclear or conflicting results. That’s why we proposed several ways to improve how future research is designed.
Improving future studies
So far, many studies have looked at the immune system in ME/CFS in a very broad way. While this has helped to reveal immune dysfunction as a key contributor to the disease, it does not yet explain why or how it happens in these individuals.
To better understand the connection between the immune system and chronic pain in ME/CFS, future studies should use more consistent approaches. This includes:
- Studying larger and comparable groups of people, while carefully taking differences such as age, sex, or other health conditions into account
- Considering variations in illness severity, and changes in symptoms over time
Using research methods which better take into account the differences between people, known as heterogeneity, may reveal different causes or processes that contribute to ME/CFS.
Transparent reporting of research methods, and use of consistent definitions, will make it easier to compare results across studies, and new technologies, such as single-cell RNA sequencing and advanced immune cell analysis, can also provide much more detailed insights; for example, into how T cells behave.
Finally, it is crucial to look at the role of lifestyle factors in future research. Standardised questionnaires about stress levels, sleep quality, exercise and a healthy diet will help researchers link biological findings to the real-life experiences of people living with ME/CFS.
