Blocking arthritis pain in the brain.

Understanding how inflammation works is becoming increasingly urgent to aging persons (like myself) who view with alarm the increasing reactivity of their innate immune system that can cause arthritic flare-ups, or autoimmune and autoinflammatory diseases such as chronic rheumatoid arthritis. Diamond and Tracey do a brief review of interesting work by Hess et al. showing that that patients with rheumatoid arthritis who receive inhibitors of TNF, a major inflammatory cytokine, develop significant changes in brain activity before resolution of inflammation in the affected joints. From their review:

During the first century, the Roman physician Cornelius Celsus defined four cardinal signs of inflammation: redness, swelling, heat, and pain. These signs and symptoms occur during infection by invasive pathogens or as a consequence of trauma. Today, we understand the molecular basis of these physiological responses as mediated by cytokines and other factors produced by cells of the innate immune system. Cytokines are both necessary and sufficient to cause pathophysiological alterations manifested as the four cardinal signs. Importantly, this knowledge has enabled the development of highly selective therapeutical agents that target individual cytokines to prevent or reverse inflammation. For example, selective inhibitors of TNF, a major inflammatory cytokine, have revolutionized the therapy of rheumatoid arthritis, inflammatory bowel disease, and other autoimmune and autoinflammatory diseases affecting millions worldwide. Now, in PNAS, Hess et al. use functional MRI to monitor brain activity and report that patients with rheumatoid arthritis who receive anti-TNF develop significant changes in brain activity before resolution of inflammation in the affected joints.

To accomplish this, the authors measured blood oxygen level-dependent (BOLD) signals in the brain after compressing the metacarpal phalangeal joints of the arthritic hand. They observe enhanced activity in the brain regions associated with pain perception, including the thalamus, somatosensory cortex, and limbic system, regions known to process body sensations and emotions associated with the pain experience ( 1). Brain activity was significantly reduced within 24 h after treatment with TNF inhibitors, a time frame that preceded any observable evidence of reduced signs of inflammation in affected joints. Clinical composite scores, comprising measurements of C-reactive protein, a circulating marker of inflammation severity, were not improved until after 24 h. This suggests that selective inhibition of TNF has a primary early effect on the nervous system pain centers.