Imaging the effects of tumour necrosis factor inhibition on pain processing in severe rheumatoid arthritis

Abstract

AbstractBackgroundMonoclonal 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.AimsThe 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.MethodsFunctional 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 checkerboard 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.ResultsTNF 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.ConclusionsTNF 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.