Probing the Rheumatoid Arthritis Brain to Elucidate Central Pain Pathways

Rheumatoid arthritis (RA) is a common disease which is characterised by severe joint inflammation and chronic pain. The discovery of new joint specific treatments has transformed patient outcomes and yet most patients, even those whose joints respond fully to these treatments, continue to experience significant levels of pain. The investigators therefore believe that RA pain is caused by alternative sources in addition to the joints. Our group are pioneering the investigation of a possible link between the brain and the pain which RA patients experience. By employing sophisticated brain scanning methods, the investigators have shown that high levels of pain and blood inflammation are associated with changes within a specific region of the brain known as the left inferior parietal lobule(L-IPL). This region exhibited abnormal connections with other brain regions already known to be associated with pain in another chronic pain disorder called fibromyalgia. Fibromyalgia is a musculoskeletal condition which is not classically related to high levels of blood inflammation, although, interestingly, it is not uncommon for it to co-exist in RA patients. In light of our preliminary brain scan studies, the investigators now think that fibromyalgia in the context of RA may be partially influenced by inflammation. In order to fully understand the precise processes that lead to this potential relationship, it is important to characterise the biological abnormalities that underlie our brain scan observations. Previous animal experiments have consistently observed abnormalities, such as high levels of the brain chemical glutamate and haphazard brain activity, in the context of inflammation. Conducting similar experiments in humans is not practical due to the inherent dangers of sampling live brain tissue. Instead, neuroscientists commonly use non-invasive methods to manipulate specific parts of the brain in order to better understand how they function. In conjunction, the latest scanners are now able to indirectly measure the effect of the brain modulation on relevant aspects of brain biology without the need to remove tissue. This information will help us to better understand the relationship between inflammation and pain in the RA brain.

Inclusion Criteria:Adults ≥ 18 years < 75 years.Physician diagnosis of RAACR definition of chronic widespread painAble and willing to maintain usual/ medication for the 6-week study durationCRP > 6mg/L or ESR > 20mm/hr•≥1 swollen jointRight-handed (to reduce neuroimaging heterogeneity)Exclusion Criteria:Inability to provide written informed consent.Severe physical impairment (e.g. blindness, deafness, paraplegia).Pregnant, planning pregnancy or breast feeding.Severe claustrophobia precluding MRI.Contraindications to MRI(e.g. metal implants/ pacemaker).Contraindication to TMS (e.g. history of seizures).