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.