Funder: Irish Research Council (IRC)
Staff: Postgraduate Scholarship to Silvano Zuccarelli (PhD candidate), supported by Dr Olga Baron
Generally, the ability to sense painful stimuli provides us with an evolutionary advantage, and indeed pain is considered to be an important signal to reduce and prevent further damage or harm to the body. Despite this, it is a lasting and very disabling symptom in patients with musculoskeletal conditions, like osteoarthritis. Prescribed therapies are often invasive or limited in effect.
Our current understanding is that in osteoarthritis the nerves that connect to the damaged arthritic joints become hypersensitive which results in previously harmless temperature or pressure stimuli to become painful. Here, antidepressant drugs can provide some relief although we don’t really fully understand how and their long-term use has severe side effects. Therefore, there is still a great need to better understand how nerve hypersensitivity develops and what can be done to influence it to provide more specific pain relief in osteoarthritis.
Our investigations are looking at specific molecules that we have shown to regulate hypersensitivity of nerves and which are encoded by genes found to be associated with osteoarthritis. By understanding how these molecules work we develop specific molecular sensors that make the nerve hypersensitivity observable. We are using these sensors to further characterise how the pain-sensing nerves become sensitive – looking at serotonergic and noradrenergic systems more specifically, with the aim to discover new strategies to resolve this sensitisation. Findings from this research will provide a deeper understanding into the pain mechanisms of osteoarthritis and may be able to provide bases for development of novel drugs to specifically target the pain-sensing nerves.