Defining the pro-nociceptive role of neutrophils in chronic widespread pain

Pain is personal, but it is typically treated through a broad-brush approach with drugs that modulate the functioning of the central nervous system. What if we could offer a personalised analgesic approach for each patient, especially for those suffering from chronic disorders such as Fibromyalgia?

This research project, co-funded by ORUK, Barts Charity, Versus Arthritis UK, Royal Society and Cancer Research UK, is analysing pain mechanisms along the Neuroimmune axis and aiming to establish whether there might be a pro-nociceptive role for neutrophils in causing Fibromyalgia-like pain. Neutrophils make up 40% to 70% of our white blood cells in humans and are central to our immune system.

According to Dr Shafaq Sikandar, Versus Arthritis Fellow and Professor of Sensory Neurophysiology at the William Harvey Research Institute, Queen Mary University of London, ‘The literature has typically classified Fibromyalgia as a brain-based disorder in which the pain syndrome is driven by psychological disturbances. Our analysis challenges this viewpoint by indicating that it is a peripherally driven pain syndrome. Research using animal models has shown that despite being very short-lived, neutrophils have the ability to infiltrate sensory ganglia, sensitize neurons and drive pain behavior.

‘What we don’t yet know is whether there is a direct cell interaction between neutrophils and primary sensory neurons, or whether the neutrophils are releasing something that then goes on to sensitize sensory neurons. We’re hoping to identify a protein signature of these pathological neutrophils to see how they interact with other surface markers on sensory neurons and identify what kind of neurons are important to drive Fibromyalgia-like pain. We want to know whether there’s a subpopulation of cells that we could target specifically, or potential molecular mediators released by those cells that we could target and prevent pain.’

Personalised medicine has typically been lacking when it comes to the treatment of pain, unlike in immune mediated conditions and in cancer where we have a better understanding of the pathology of a disease and how to target the pathological mechanism. In part this reflects the difficulty of measuring pain, Dr Sikandar says, ‘Pain is a whole-body experience and highly complex. It has a sensory and psychological component. When a patient comes into a clinic, they’re more likely to be catastrophizing or suffering from high levels of anxiety that might be exacerbating and amplifying their pain experience. If we can find an objective biomarker of pain, allowing us to have distinct signatures for chronic pain for different diseases, it opens-up the possibility of more targeted and personalised approaches.’

In addition to Dr Shafaq Sikandar, the team involved in this research project are:

• Dr Sara Caxaria
• Dr Alice Fuller
• Ms Romy Evans