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Clinical trial

Imaging Pain Relief in Osteoarthritis

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Last updated:4th Aug 2014

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 control condition. With this we also aim to identify genetic and brain activity predictors of treatment outcomes.

We hypothesise that:

- The antinociceptive effect of both duloxetine and remifentanil is mediated by improving endogenous pain inhibition through normalisation of functional connectivity and acute pain processing;

- The extent of defunct cortical control of pain processing networks at baseline predicts treatment response at 6 weeks;

- The antinociceptive effects of duloxetine is partially mediated by ts anxiolytic effect as indexed by reduction of amygdala activation.

This study is expected to last for two years. It is funded by Arthritis Research UK and forms part of a wider scientific investigation, using translational methodologies, to enhance the understanding of arthritis pain and to improve its treatment.

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Study start date 2014-08-04

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