Imaging Pain Relief in Osteoarthritis

Osteoarthritis (OA) is a degenerative joint disease and is the most common form of arthritis. Pain reduction and functional recovery are the key elements of the clinical management of OA. Current treatment guidelines recommend a combination of pharmacological and non-pharmacological treatments. However, these are not always effective, with nearly 20% of patients not responding to any standard therapy, including joint replacement. The mechanisms of pain relief are not well understood and are complicated by the remarkably large placebo effect, and inter-individual variation. There is no objective criteria for predicting whether a patient will respond to a given treatment Duloxetine, an antidepressant drug, has proven effectiveness in various chronic pain syndromes including knee OA. The effect is however limited and only clinically relevant in around half of the trial patients. Importantly, it is currently unclear how and in whom duloxetine alleviates chronic pain. Advanced MRI techniques use strong magnetic fields and radio frequency signals to generate metabolic, anatomical and functional brain images (fMRI). Remifentanil is a potent analgesic agent whose analgesic effect has been well characterised in healthy volunteers, including fMRI studies showing modulation of activation of regions in the brain related to pain processing. Nevertheless, the neural correlates of remifentanil effects have not yet been investigated in chronic pain patients. The aim of this research is to use a combination of multimodal MRI, genetic and psychometric assessments to identify the mechanisms of pain relief in knee OA patients, following treatments with duloxetine and remifentanil, in a placebo controlled condition. With this we also aim to identify genetic, anatomical and brain activity predictors of treatment outcomes. The main hypotheses are: * Analgesic response to duloxetine treatment can be predicted using a range of baseline brain imaging markers and QST. * Analgesic response to duloxetine is mediated by modulation of neural networks underpinning emotional control. * Duloxetine-induced changes in brain activation differ between responders and non-responders. This study is expected to last for two years. It is funded by Arthritis Research United Kingdom and forms part of a wider scientific investigation, using translational methodologies, to enhance the understanding of arthritis pain and to improve its treatment.