Florea, Roxana; (2025) Exploring Environmental Influences on Sensory Perception, Emotional Responses, and Molecular Signalling in Joint Pain. Doctoral thesis (Ph.D), UCL (University College London).

Text Roxana Florea PhD Thesis.pdf - Accepted Version Access restricted to UCL open access staff until 1 May 2026. Download (11MB)

Abstract

Despite decades of research, chronic pain remains a significant clinical challenge, with an urgent need for novel therapies. Joint pain resulting from osteoarthritis (OA) is one of the most prevalent forms of chronic pain and is the hallmark symptom prompting OA patients to seek medical care. However, treatment efficacy remains limited, partly because of a lack of correlation between joint damage and pain intensity, suggesting the existence of altered central pain processing. While environmental factors, such as stress and physical activity, are known to influence pain symptoms, the role of stressful life experiences in shaping OA pain susceptibility remains poorly understood, and the benefits of exercise induced pain relief are not yet fully consolidated. First, the impact of subchronic stress exposure in adulthood on the subsequent pain experience in the MIA model of OA was examined. In male mice, prior stress exposure attenuated pain-like responses and reversed anxiety-like behaviours, suggesting that stress promoted a resilient phenotype. These observations were accompanied by dampening in the expression of the neuronal activity marker c-Fos. Interestingly, female mice exhibited a vulnerable phenotype with no obvious trends at the molecular level. Then, the impact of voluntary wheel running on the pain experience in the MIA model was explored, using two different social housing conditions: solitary or group housing. Wheel running provided mild improvements on mechanical allodynia, with no other substantial differences observed at the molecular or behavioural level between conditions, likely due to the limitations of the preclinical set-ups used. These findings provide the first evidence that stress exposure in adulthood modulates subsequent pain and affective outcomes in a preclinical mouse model of OA, highlighting an underexplored factor that may contribute to pain variability in OA patients. Additionally, the study underscores key experimental considerations for evaluating the therapeutic potential of voluntary exercise in preclinical settings.

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