Background: Monoclonal antibodies against tumour necrosis factor (TNF) markedly reduce inflammation and disease activity in rheumatoid arthritis; however, the mechanisms through which they affect pain are not fully understood. Aims: The aim of this study was to investigate how monoclonal antibodies against TNF alter pain processing and to determine whether neuroimaging can be used as a marker of treatment efficacy and a predictor of treatment response. Methods: Functional magnetic resonance imaging was used to study the neural correlates of clinically-relevant pain evoked by pressing the most painful joint of the right hand and experimental pain evoked by a thermal stimulus applied to the right forearm. A flashing chequerboard was used as a control stimulus. Patients with severe rheumatoid arthritis, qualifying for the anti-TNF treatment, were scanned before the beginning of the therapy and then approximately one and six months after the first injection. Results: TNF inhibition was associated with a marked reduction in pain ratings, inflammation, disease activity as well as depression and catastrophising scores. Effective treatment was linked with less pressure-evoked brain activation in the regions involved in the processing of the sensory aspect of pain and in the limbic structures. Baseline pressure-evoked activation in the thalamus predicted future response to treatment. There was no reduction in heat-evoked brain activation; on the contrary, there was an increase in the activation in the precuneus, which is involved in interoception. There were no differences in response to the visual stimulus. Conclusions: TNF inhibition strongly reduces brain activation in response to clinically relevant pressure pain but not experimental heat pain and these changes reflect the decrease of nociceptive input from the periphery due to the reduction of inflammation as well as central changes in pain modulation. Neuroimaging methods have the potential to explain and predict treatment effects in inflammatory pain conditions.

This research project was supported by unrestricted grants from GlaxoSmithKline (KW), the Wellcome Trust (IT), the Biotechnology and Biological Sciences Research Council - David Phillips Fellowship (MJ) and the Medical Research Council of Great Britain and Northern Ireland (FMRIB Centre). There was no conflict of interest. The funding bodies had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

This research project was supported by unrestricted grants from GlaxoSmithKline (KW), the Wellcome Trust (IT), the Biotechnology and Biological Sciences Research Council - David Phillips Fellowship (MJ) and the Medical Research Council of Great Britain and Northern Ireland (FMRIB Centre). There was no conflict of interest. The funding bodies had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

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The study was approved by the Oxfordshire Research Ethics Committee and conducted in accordance with the principles of the Declaration of Helsinki.

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