Exploring the role of the immune system in maladaptive pain sensitisation

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In a physiological setting, pain sensitisation is a protective mechanism that functions to prevent further tissue damageand promote healing. At a cellular level, this is characterised by an increased responsiveness of nociceptors, owed to adecrease in threshold for neuronal firing and/or increase in the scale of the response. However, in a pathological setting,inappropriate pain sensitisation is a key feature of many debilitating disorders, including rheumatoid arthritis (RA). As achronic inflammatory disease, the pain sensitisation in RA is accompanied by the recruitment and infiltration of bloodderived immune cells to the synovial membrane of joints, these include lymphocytes, macrophages and neutrophils. Atthe synovium these immune cells promote inflammation by releasing proinflammatory mediators such as interleukin (IL)-1B, IL-6 and tumour necrosis factor a. Recently, evidence has emerged to suggest interactions between the secretedproinflammatory proteins and receptors present on nociceptors, which may play a role in facilitating pain sensitisation.However, these intercellular interactions and underlying mechanisms are yet to be fully understood. Here, this projectaims to employ a combination of research methods, ranging from primary cell cultures to in vivo models and PCR tobehavioural experiments, to delineate the role of blood derived immune cells in the sensitisation of peripheralnociceptors.This may ultimately have implications for future therapeutics.